Anti-C1q como Marcador de Nefritis Lúpica / Anti-C1q as Lupus Nephritis Marker

Introducción: Los autoanticuerpos anti-C1q han sido propuestos como un marcador útil en el lupus eritematoso sistémico por su asociación con la nefritis lúpica. Objetivo: Determinar la prevalencia de anti-C1q en pacientes con lupus eritematoso sistémico y otras enfermedades reumáticas para la evaluar la asociación con la nefropatía lúpica. Métodos: Se incluyeron 179 pacientes con lupus eritematoso sistémico y 82 con otras enfermedades reumáticas. La nefritis lúpica fue diagnosticada en 70 (39 por ciento) de los pacientes con lupus eritematoso sistémico. Los anticuerpos anti-C1q IgG se determinaron por ELISA. Las asociaciones se evaluaron por análisis de regresión logística. Resultados: La prevalencia de anti-C1q fue de 37 poe ciento (66/179) en los pacientes con lupus eritematoso sistémico y de 9 por ciento (7/82) en controles (OR = 6,3; IC 95 por ciento 2,8-14,1; p < 0,001). El anti-C1q fue asociado con proteinuria (OR = 2,6; IC 95 por ciento 1,2-6,0; p < 0,022); eritrosedimentación elevada (OR = 3,2; IC 95 por ciento 1,5-6,7; p < 0,003) y anti-DNAdc (OR = 3,9; IC 95 por ciento 1,7-9,1; p < 0,002). En el modelo de regresión logística ajustado para demografía y anti-DNAdc, aunque la OR del anti-C1q para la nefritis fue 2 veces más alta que en ausencia del anti-C1q, solo se aproximó a la significación estadística. La positividad simultánea de anti-C1q y anti-DNAdc estuvo asociada a la nefritis lúpica (OR = 4,3; IC 95 por ciento 1,9-9,5; p < 0,001). Conclusiones: El anti-C1q se presentó con mayor frecuencia en pacientes con lupus eritematoso sistémico que en los controles. El anti-C1q combinado con anti-DNAdc resultó fuertemente asociado a la nefritis lúpica(AU)

Introducción: Anti-C1q autoantibodies have been proposed as useful marker in systemic lupus erythematosus due to their association with lupus nephritis. Objective: To determine the prevalence of anti-C1q in patients with systemic lupus erythematosus and other rheumatic diseases to evaluate the association with lupus nephropathy. Methods: One hundred seventy-nine patients with systemic lupus erythematosus and 82 with other rheumatic diseases were included. Lupus nephritis was diagnosed in 70 (39percent) of patients with systemic lupus erythematosus. Anti-C1q IgG antibodies were determined by ELISA. Associations were evaluated by logistic regression analysis. Results: The prevalence of anti-C1q was 37percent (66/179) in patients with systemic lupus erythematosus and 9percent (7/82) in controls (OR = 6.3; 95percent CI 2.8-14). .1; p < 0.001). Anti-C1q was associated with proteinuria (OR = 2.6; 95percent CI 1.2-6.0; p < 0.022); elevated erythrocyte sedimentation rate (OR = 3.2; 95percent CI 1.5-6.7; p < 0.003) and anti-dsDNA (OR = 3.9; 95percent CI 1.7-9.1; p < 0.002). In the logistic regression model adjusted for demographics and anti-dsDNA, although the OR of anti-C1q for nephritis was 2-fold higher than in the absence of anti-C1q, it only approached statistical significance. Simultaneous positivity of anti-C1q and anti-dsDNA was associated with lupus nephritis (OR = 4.3; 95percent CI 1.9-9.5; p < 0.001). Conclusions: Anti-C1q occurred more frequently in patients with systemic lupus erythematosus than in controls. Anti-C1q combined with anti-dsDNA was strongly associated with lupus nephritis(AU)

Lupus eritematoso sistémico pediátrico asociado a hepatitis autoinmune y síndrome nefrítico: Reporte de un caso y revisión de la literatura / syndrome: A case report and review of the literature

Introducción: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que puede afectar a múltiples órganos. Las patologías asociadas como: la hepatitis y la nefritis lúpica no son frecuentes en la población infantil, pero conllevan a consecuencias graves con riesgo de insuficiencia hepática y enfermedad renal crónica, aumentando la mor-bimortalidad en los pacientes pediátricos. Caso clínico: Paciente masculino de 11 años con cuadro clínico caracterizado por: astenia, hiporexia, epistaxis, prurito e ictericia marcada, de cuatro meses de evolución, sin diagnóstico establecido. Se solicitó estudios de laboratorio que reportaron aumento de transaminasas, proteinuria, ANAS y AC. DNA positivo, además se realizaron estudios de imagen, biopsia renal y hepática, con la finalidad de esclarecer el diagnóstico. Evolución: A través de un abordaje clínico multidisciplinar, exámenes paraclínicos y anatomopatológicos se estableció el diagnóstico de LES asociado a Hepatitis Autoinmune y Nefritis Lúpica. Paciente permaneció en la Unidad de Cuidados Intensivos Pediátricos con evolución favorable a tratamiento. Conclusiones: El LES Pediátrico asociado a hepatitis autoinmune y nefritis lúpica es una rara presentación clínica de la cual existen muy pocos casos reportados a nivel mundial. En su diagnóstico se debe resaltar la perspicacia clínica multi-disciplinar, laboratorio, imagenología y datos histopatológicos clave para establecer un diagnóstico oportuno con mejor pronóstico y tratamiento y así evitar desenlaces mortales en los pacientes pediátricos.

Introduction: Systemic lupus erythematosus is an autoimmune disease that can affect multiple organs. Associated pathologies such as hepatitis and lupus nephritis are not frequent in the child population. Still, they lead to serious consequences with the risk of liver failure and chronic kidney disease, increasing morbidity and mortality in pediatric patients. Clinical case: An 11-year-old male patient with a clinical picture characterized by: asthenia, hypoxia, epistaxis, pruritus, and marked jaundice, of four months of evolution, without an established diagnosis. Laboratory studies were requested that reported increased transaminases, proteinuria, ANAS, and AC. Positive DNA, imaging studies, and kidney and liver biopsy were also performed to clarify the diagnosis. Evolution: Through a multidisciplinary clinical approach, and paraclinical and pathological examinations, the diagnosis of Systemic Lupus Erythematosus associated with Autoimmune Hepatitis and Lupus Nephritis was established. The patient remained in the Pediatric Intensive Care Unit with favorable evolution to treatment. Conclusions: Pediatric Systemic Lupus Erythematosus associated with autoimmune hepatitis and lupus nephritis is a rare clinical presentation of which very few cases are reported worldwide. In its diagnosis, multidisciplinary clinical acumen, laboratory, imaging, and critical histopathological data should be highlighted to establish an opportune diagnosis with better prognosis and treatment and thus avoid fatal outcomes in pediatric patients.

The expression of autophagy-related proteins in peripheral blood mononuclear cells of patients with lupus nephritis is upregulated and related to kidney damage / 细胞与分子免疫学杂志

Objective To identify the relationship between nephritis activity, autophagy and inflammation in patients with SLE. Methods Western blot analysis was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3) and P62 in peripheral blood mononuclear cells (PBMCs) of SLE patients with lupus nephritis and non-lupus nephritis patients. Tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) in the serum of SLE patients were determined by ELISA. The correlation between LC3II/LC3I ratio and SLE disease activity score (SLEDAI), urinary protein, TNF-α and IFN-γ levels was analyzed by Pearson method. Results The expression of LC3 was increased and P62 was decreased in SLE patients. TNF-α and IFN-γ were increased in the serum of SLE patients. LC3II/LC3I ratio was positively correlated with SLEDAI (r=0.4560), 24 hour urine protein (r=0.3753), IFN-γ (r=0.5685), but had no correlation with TNF-α (r=0.04 683). Conclusion Autophagy is found in PBMCs of SLE, and the autophagy is correlated with renal damage and inflammation in patients with lupus nephritis.

Risk factors of childhood systemic lupus erythematosus with thyroid dysfunction / 中华儿科杂志

Objective: To investigate the risk factors of childhood systemic lupus erythematosus (SLE) with thyroid dysfunction and to explore the relationship between thyroid hormone and kidney injury of lupus nephritis (LN). Methods: In this retrospective study, 253 patients who were diagnosed with childhood SLE and hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2019 to January 2021 were enrolled in the case group, and 70 healthy children were the control cases. The patients in the case group were divided into the normal thyroid group and the thyroid dysfunction group. Independent t-test, χ2 test, and Mann-Whitney U test were used for comparison between the groups, Logistic regression analysis was used for multivariate analysis, and Spearman correlation. Results: A total of 253 patients, there were 44 males and 209 females in the case group, and the age of onset was 14 (12, 16) years; a total of 70 patients, 24 males and 46 females were in the control group, and the age of onset was 13 (10, 13) years. The incidence of thyroid dysfunction in the case group was higher than that in the control group (48.2% (122/253) vs. 8.6% (6/70), χ²=36.03, P<0.05). Of the 131 patients, there were 17 males and 114 females in the normal thyroid group, and the age of onset was 14 (12, 16) years. Of the 122 patients in the thyroid dysfunction group, 28 males and 94 females were in the thyroid dysfunction group, and the age of onset was 14 (12, 16) years. Of the 122 had thyroid dysfunction, including 51 cases (41.8%) with euthyroid sick syndrome, 25 cases (20.5%) with subclinical hypothyroidism, 18 cases (14.8%) patients with sub-hyperthyroidism, 12 cases (9.8%) with hypothyroidism, 10 cases (8.2%) with Hashimoto's thyroiditis, 4 cases (3.3%) with hyperthyroidism, and 2 cases (1.6%) with Graves disease. Compared to patients with normal thyroid function, the serum level of triglyceride, total cholesterol, urine white blood cell, urine red blood cell, 24 h urine protein, D-dimer, and fibrinogen, ferritin and systemic lupus erythematosus disease activity Index-2000 (SLEDAI-2K) score were higher in patients with thyroid dysfunction (Z=3.07, 3.07, 2.48, 3.16, 2.40, 3.99, 2.68, 2.55, 2.80, all P<0.05), while the serum level of free thyroxine and C3 were lower in thyroid disfunction patients (10.6 (9.1, 12.7) vs. 11.3 (10.0, 12.9) pmol/L, and 0.46 (0.27, 0.74) vs. 0.57 (0.37, 0.82) g/L, Z=2.18, 2.42, both P<0.05). The higher level of triglyceride and D-dimer were the independent risk factors for childhood SLE with thyroid dysfunction (OR=1.40 and 1.35, 95%CI 1.03-1.89 and 1.00-1.81, respectively, both P<0.05). There were 161 patients with LN in the case group, all of which were conducted with renal biopsies, including 11 cases (6.8%) with types Ⅰ LN, 11 cases (6.8%) with typesⅡLN, 31 cases (19.3%) with types Ⅲ LN, 92 cases (57.1%) with types Ⅳ LN, and 16 cases (9.9%) with types Ⅴ LN. There were significant differences in the level of free triiodothyronine and thyroid stimulating hormone among different types of kidney pathology (both P<0.05); compared with types I LN, the serum level of free triiodothyronine was lower in types Ⅳ LN (3.4 (2.8, 3.9) vs. 4.3 (3.7, 5.5) pmol/L, Z=3.75, P<0.05). The serum level of free triiodothyronine was negatively correlated with the acute activity index score of lupus nephritis (r=-0.228, P<0.05), while the serum level of thyroid stimulating hormone was positively correlated with the renal pathological acute activity index score of lupus nephritis (r=0.257, P<0.05). Conclusions: There is a high incidence of thyroid dysfunction in childhood SLE patients. The higher SLEDAI and more severe renal damage were found in SLE patients with thyroid dysfunction compared to these with normal thyroid functions. The risk factors of childhood SLE with thyroid dysfunction are the higher level of triglyceride and D-dimer. The serum level of thyroid hormone is possibly related to the kidney injury of LN.

Belimumabe comparado à terapia padrão do Sistema Único de Saúde no tratamento da nefrite lúpica nos estágios III, IV e V: revisão rápida / Belimumab compared to standard therapy of the Brazilian Public Health System in the treatment of lupus nephritis in stage III, IV, and V: rapid review

Belimumabe, rituximabe, terapia imunossupressora. Indicação: Nefrite lúpica nos estágios III, IV, V, refratária à terapia imunossupressora. Pergunta: Belimumabe é eficaz (remissão da nefrite, normalização da perda da função renal, qualidade de vida) e seguro (descontinuação devido a eventos adversos totais e eventos adversos graves) para o tratamento de pacientes com nefrite lúpica refratária nos estágios III, IV, V em comparação aos medicamentos disponíveis no Sistema Único de Saúde? Objetivo: Avaliar a segurança e eficácia do belimumabe em comparação com os medicamentos disponíveis no Sistema Único de Saúde em pacientes adultos com nefrite lúpica. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionadas duas revisões sistemáticas que atendiam aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: a terapia combinada de belimumabe, ou de rituximabe, com tratamento imunossupressor padrão é mais eficaz que o tratamento padrão para alcançar remissão clínica da nefrite lúpica. A terapia combinada é tão segura quanto o tratamento padrão. Belimumabe e rituximabe tem eficácia similar entre si

Belimumab, rituximab, and immunosuppressive therapy. Indication: Refractory lupus nephritis to immunosuppressive therapy in stages III, IV, V. Question: Is belimumab effective (for remission of nephritis, normalization of loss of renal function, quality of life) and safe (for discontinuation due to total adverse events and serious adverse events) in the treatment of patients with refractory lupus nephritis in stages III, IV, V compared to the drugs available in the Brazilian Public Health System? Objective: To evaluate the safety and efficacy of belimumab compared to drugs available in the Brazilian Public Health System in adult patients with lupus nephritis. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library databases and in records of systematic reviews and clinical trials. It has followed predefined search strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: Two systematic reviews were selected, which met the eligibility criteria, but no clinical trials were chosen, as they did not meet the inclusion criteria. Conclusion: Combination therapy of belimumab or rituximab with standard immunosuppressive treatment is more effective than standard treatment in achieving clinical remission of lupus nephritis. Combination therapy is as safe as standard treatment. Belimumab and rituximab have similar efficacy to each other

Clinical and immunological factors associated with lupus nephritis in an Argentine patient population: A cross-sectional study

Introduction: In recent decades, the prevalence of systemic lupus erythematosus (SLE) has increased thanks to early detection and the impact of new therapies on the survival of those affected. Up to 90% will have histopathological signs of kidney disease in the first 3 years of the disease, but lupus nephritis of clinical relevance will appear in 50% of cases, affecting kidney function and mortality. Despite aggressive therapeutic strategies, the prognosis of patients with LN remains unfavourable, mainly due to the high risk of progression to end-stage renal disease (10%-20%) and mortality from all causes. Objective: To describe the clinical and immunological risk factors of a group of patients with lupus, comparing clinical and serological characteristics in relation to renal involvement to establish possible associations. Materials and methods: Cross-sectional study in which 87 patients with SLE were included. Clinical and immunological variables were analyzed. Bivariate and multivariate analyses were performed using the presence of nephritis as an outcome. Results: The prevalence of lupus nephritis was 59%. The significantly associated variables were arterial hypertension (OR 3.1, 95% CI 1.02-9.40), age of onset of lupus less than 25 years (OR 2.7, 95% CI 1.08-6.73), the presence of reticular livedo (OR 4.1, 95% CI 1.09-15.7), positive anti-DNA (OR 2.9, 95% CI 1.18-7.24) and low levels of complement (OR 4.0, 95% CI 1.64-10.2). Conclusions: Urinary sediment abnormalities were the most common renal manifestation and lupus debut before the age of 25 seems to increase the risk of developing nephritis. Future research is required for a better explanation of the associations found.

Introducción: En las últimas décadas, la prevalencia del lupus eritematoso sistémico (LES) se ha incrementado gracias a la detección temprana y al impacto de las nuevas terapias en la sobrevida de los afectados. Hasta el 90% de ellos tendrá signos histopatológicos de afección renal en los primeros 3 arios de la enfermedad, pero la nefritis lúpica (NL) de relevancia clínica aparecerá en el 50% de los casos, afectando la función renal y la mortalidad. A pesar de las estrategias terapéuticas agresivas, el pronóstico de los pacientes con NL sigue siendo desfavorable, principalmente debido al alto riesgo de progresión a enfermedad renal crónica terminal (10-20%) y de mortalidad por todas las causas. Objetivo: Describir los factores de riesgo clínicos e inmunológicos de un grupo de pacientes con lupus, comparando características clínicas y serológicas en relación con el compromiso renal, a fin de establecer posibles asociaciones. Materiales y métodos: Estudio de corte transversal en el que se incluyeron 87 pacientes con LES. Se analizaron variables clínicas e inmunológicas. Los análisis bivariado y multivariados se realizaron utilizando la presencia de nefritis como desenlace. Resultados: La prevalencia de NL fue del 59%. Las variables asociadas significativamente fueron hipertensión arterial (OR: 3,1; IC 95%: 1,02-9,40), edad de aparición del lupus menor de 25 años (OR: 2,7; IC 95%: 1,08-6,73), presencia de livedo reticularis (OR: 4,1; IC 95%: 1,0915,7), anti-DNA positivo (OR: 2,9; IC 95%: 1,18-7,24) y niveles bajos de complemento (OR: 4,0; IC 95%: 1,64-10,2). Conclusiones: Las anormalidades en el sedimento urinario fueron la manifestación renal más común, en tanto que el inicio lúpico antes de los 25 años parece incrementar el riesgo de desarrollar nefritis. Se requieren futuras investigaciones que den una mejor explicación a las asociaciones encontradas.

Direct costs associated with lupus nephritis management in the Private Healthcare System in Brazil: an expert panel perspective / Custos diretos associados ao manejo da nefrite lúpica no Sistema de Saúde Privado no Brasil: uma perspectiva segundo painel de especialistas

Objective: To estimate direct medical costs of lupus nephritis (LN) in the Brazilian private healthcare system. Methods: An expert panel of five specialists were convened to discuss health resource usage in LN patient management. The discussion included diagnosis, treatment, and disease monitoring, including dialysis and kidney transplantation. Unit costs (in BRL) were obtained from public sources, and an estimation of 1-year costs was conducted. Results: Approximately 76.0% of patients with LN undergo kidney biopsy, of which 48.1% present with LN classes III­IV and 21.4% have class V. Around 67.5% of patients with LN classes III­IV experience an average of four renal flares annually. Overall, 20.3% of patients present refractory LN, and 10.3% have end-stage kidney disease (ESKD), requiring dialysis and kidney transplantation. Estimated total weighted annual costs per patient were BRL 115,824.81 for LN classes III­IV, BRL 85,684.79 for LN class V, BRL 115,594.98 for refractory LN; and BRL 325,712.88 for ESKD. The main annual cost driver for LN classes III­IV was renal flares (BRL 60,240.41; 52.0%) and dialysis for LN class V (BRL 31,128.38; 36.3%). Conclusions: Total direct costs increase when LN progresses to ESKD. Although it is challenging to improve the diagnosis, identification of the disease at an early stage, together with rapid initiation of treatment, are fundamental elements to optimize results, potentially reducing costs to the system and the impact of disease burden and quality of life on patients.

Objetivo: Estimar os custos médicos diretos da nefrite lúpica (NL) no sistema suplementar de saúde brasileiro. Métodos: Um painel de cinco especialistas foi estruturado para discutir o uso de recursos em saúde no manejo de pacientes com NL. Nesta discussão, incluíram-se o diagnóstico, o tratamento e o monitoramento da doença, contemplando também diálise e transplante renal. Os custos unitários foram obtidos de fontes públicas e os resultados expressos em custo anual. Resultados: Aproximadamente 76,0% dos pacientes com NL são submetidos à biópsia renal, sendo 48,1% com NL de classes III-IV e 21,4% de classe V. Cerca de 67,5% dos pacientes com classes III-IV apresentam, aproximadamente, quatro flares renais anuais. No geral, 20,3% dos pacientes apresentam NL refratária e 10,3% desenvolvem doença renal terminal (DRT), necessitando de diálise e transplante renal. O custo ponderado anual estimado por paciente foi de R$ 115.824,81 para NL de classes III-IV, R$ 85.684,79 para classe V, R$ 115.594,98 para NL refratária e R$ 325.712,88 para DRT. O principal fator para incremento dos custos anuais para NL de classes III-IV foram os flares renais (R$ 60.240,41; 52,0%) e, na classe V, a diálise (R$ 31.128,38; 36,3%). Conclusões: Há um incremento dos custos diretos da NL na progressão para DRT. Embora seja desafiador melhorar o diagnóstico, a identificação da doença em uma fase precoce, aliada ao tratamento iniciado de forma célere, são elementos fundamentais para otimizar os resultados, potencialmente reduzindo os custos ao sistema e o impacto da carga da doença e qualidade de vida dos pacientes.

Mielite transversa por Zika vírus em paciente com Lúpus Eritematoso Sistêmico (LES) - relato de caso em Manaus - AM / Transverse myelitis by Zika virus in patient with Systemic Lupus Erythematosus (SLE) - case report in Manaus - AM

Objetivo: Relatar caso clinico de uma paciente com Mielite Transversa diagnosticada com Lúpus Eritematoso Sistêmico e Zika Vírus. Relato de Caso: Paciente diagnosticada em Lúpus Eritematoso Sistêmico (LES) com nefrite lúpica classe IV há 15 anos em remissão, iniciou quadro de mialgia difusa prejudicando deambulação. Após melhora espontânea do quadro, paciente permaneceu com queixa de astenia e cefaleia intensa unilateral esquerda recorrente, evoluindo com síncope, paraparesia em membro inferior em caráter progressivo ascendente seguido de crise convulsiva tipo tônico clônico generalizado de inicio disruptivo. Um primeiro exame do liquor cefalorraquidiano (LCR) foi solicitado, sem evidência de alteração na analise bioquímica simples. Outras alterações laboratoriais foram identificadas, além do método de reação em cadeia de polimerase (PCR) para Zika vírus na urina e liquor cefalorraquqidiano (após recoleta) detectáveis. Foram detectadas alterações à ressonância magnética compatíveis com mielite transversa. A investigação etiológica durou dois meses e meio, com duas internações no período. Apesar das manifestações neurológicas do Zika Vírus serem ordinariamente inespecíficas, raras e brandas, não se deve desconsiderar a hipótese diagnostica de mielite transversa em área endêmica para arboviroses com manifestações neurológicas mesmo após liquor cefalorraquidiano e outros exames inespecíficos com o achado clínico, considerando paciente remissiva do quadro de lupus eritematoso sistêmico há 15 anos

Objective: case report of a patient with transverse myelitis diagnosed with systemic lupus erythematosus and zika Virus. Case report: Patient diagnosed with Systemic Lupus Erythematosus (SLE) with class IV lupus nephritis for 15 years in remission, begins to have diffuse myalgia, impairing walking. After spontaneous improvement of the condition, the patient remained complaining of asthenia and recurrent left unilateral severe headache, evolving with syncope, progressive ascending paraparesis in the lower limb, followed by a generalized tonic clonic seizure type of disruptive onset. A first examination of the cerebrospinal fluid (CSF) was requested, without evidence of alteration in the simple biochemical analysis. Other laboratory alterations were identified, in addition to the polymerase chain reaction (PCR) for detectable Zika virus in urine and cerebrospinal liquor (after collection). Changes were detected on magnetic resonance imaging (MRI) compatible with transverse myelitis. The etiological investigation lasted two and a half months, with two hospitalizations in the period. Although the neurological manifestations of Zika Virus are ordinarily nonspecific, rare and mild, the diagnostic hypothesis of transverse myelitis in an endemic area for arboviruses with neurological manifestations should not be disregarded even after cerebrospinal fluid and unspecific with the other clinical, remissive of the clinical picture lupus erythemasous systemic 15 years ago.

Nefritis como debut lúpico en el embarazo: reporte de dos casos y revisión de la literatura / Nephritis as a lupic debut in pregnancy: report of two cases and review of the literature

ANTECEDENTES: El lupus eritematoso sistémico es una enfermedad autoinmunitaria multisistémica que afecta principalmente a mujeres en edad fértil. La nefritis lúpica es la manifestación clínica más frecuente durante la gestación y constituye un factor de riesgo para la pérdida del embarazo, en especial en pacientes con insuficiencia renal. Además, presenta mayor riesgo de pérdida fetal, restricción del crecimiento intrauterino e hipertensión. CASOS CLÍNICOS: El primer caso se trata de una gestante de 28 + 2 semanas con daño renal grave y anticuerpos anti-DNA en título elevado. En el segundo caso destaca el debut con sintomatología de dificultad respiratoria y edemas como manifestaciones clínicas de nefropatía lúpica tipo V a las 23 semanas de gestación. En ambas pacientes destaca la prematuridad como complicación perinatal, así como el crecimiento intrauterino retardado en el primer caso. Por último, se describen los resultados clínico-analíticos tras el inicio terapéutico específico en ambos casos. CONCLUSIONES: El diagnóstico diferencial del debut de nefritis lúpica durante la gestación continúa siendo un desafío, a pesar de los avances en cuanto a marcadores angiogénicos. La valoración clínica continúa siendo la piedra angular de este proceso diagnóstico y de sus implicaciones en cuanto a complicaciones del embarazo actuales y futuras.

BACKGROUND: Systemic lupus erythematosus is a multisystem autoimmune disease that mainly affects women of childbearing age. Lupus nephritis represents the most frequent clinical manifestation in pregnancy, constituting a risk factor for pregnancy loss, especially in patients with kidney damage. It also has a higher risk of fetal loss, intrauterine growth restriction, and gestational hypertension. CLINICAL CASES: The first case is a 28 + 2-week pregnant woman with severe kidney damage and high-titles anti-DNA antibodies. In the second case, we highlight the debut with symptoms of respiratory distress and edema as clinical manifestations of type V lupus nephropathy in a 23-week gestation. In both cases, prematurity stands out as a perinatal complication, as well as delayed intrauterine growth in the former. Finally, the clinical-analytical results are described, after the specific therapeutic initiation in both cases. CONCLUSIONS: The differential diagnosis of the onset of lupus nephritis during pregnancy continues to be a challenge, despite the advances in angiogenic markers; clinical assessment continues to be the cornerstone of this diagnostic process and its implications for current and future pregnancy complications.

The value of repeat kidney biopsy in lupus nephritis. A systematic review / La utilidad de la biopsia renal repetida en nefritis lúpica. Una revisión sistemática

ABSTRACT A renal biopsy is the 'gold standard' for diagnosis and classification of lupus nephritis (LN). The role of repeat renal biopsy in lupus nephritis (LN) to guide treatment or predict prognosis has been controversial. A systematic literature review was conducted based on retrospective and prospective studies. The studies were identified using English electronic scientific databases, including MEDLINE PUBMED, published between January 1990 and August 2020. The eligibility criteria were studies including adult LN patients with at least one follow-up renal biopsy with appropriate longitudinal information. Case reports, studies with incomplete information or including duplicate patients were excluded. Based on the inclusion and exclusion criteria, a total of 73 publications were identified. This study included a total of 1167 repeat biopsies in LN patients from 15 studies. The primary indication for a repeat biopsy was relapse in 44-78% of the cases, and lack of response in 13-51%. Additionally, several repeat biopsies were done according to the protocol, after induction and maintenance therapy. In terms of histopathological class switches, there was a higher frequency of changes from nonproliferative to proliferative lesions. Only two studies provide a definition of histological response. There were often changes in the therapeutic approach after a repeat biopsy. Repeat kidney biopsies are helpful in patients with LN flare/relapse, and in patients with poor treatment response. Histological transformation was a common finding. The histologic and clinical responses are discordant. A repeat biopsy could be of prognostic value for therapeutic decision-making.

RESUMEN La biopsia renal es el «estándar de oro¼ para el diagnóstico y la clasificación de la nefritis lúpica (NL). El papel de la biopsia renal repetida en nefritis lúpica para orientar el tratamiento o predecir el pronóstico ha sido controversial. Se llevó a cabo una revisión sistemática de la literatura basada en estudios retrospectivos y prospectivos. Los estudios se identificaron a través de bases de datos científicas electrónicas en inglés, incluyendo Medline PubMed, de publicaciones entre enero de 1990 y agosto del 2020. Los criterios de elegibilidad fueron estudios que incluyeran a pacientes adultos con NL, quienes tuvieran al menos una biopsia renal de seguimiento, con información longitudinal apropiada. Se excluyeron informes de casos, estudios con información incompleta o con pacientes duplicados. Basándose en los criterios de inclusión y exclusión, se identificaron 73 publicaciones. En la presente revisión se analizaron un total de 1.167 biopsias repetidas en pacientes con NL en 15 estudios. Las principales indicaciones para la biopsia repetida fueron: recidiva en 44-78% de los casos, y falta de respuesta en 13-51%. Adicionalmente, varias biopsias repetidas se hicieron conforme al protocolo, luego de la terapia de inducción y de mantenimiento. Con respecto a los cambios de clase histopatológica, hubo una mayor frecuencia de cambios de lesiones no proliferativas a lesiones proliferativas. Solamente dos estudios ofrecen una definición de respuesta histológica. Con frecuencia hubo cambios en el abordaje terapéutico después de realizar la biopsia repetida. Las biopsias renales repetidas son útiles en pacientes con exacerbación/recidiva y en pacientes con falta de respuesta a tratamiento. La transformación histológica fue un hallazgo frecuente; las respuestas histológicas y clínicas son discordantes. Una biopsia repetida puede ser de valor pronóstico para la toma de decisiones terapéuticas.

Understanding tubulointerstitial injury and repair mechanisms paves the way for renal outcome improvement in lupus nephritis / Entender la lesión tubulointersticial y los mecanismos de reparación será la vía para mejorar los desenlaces renales en nefritis lúpica

ABSTRACT Despite improvements in patient survival and quality of life, long-term renal survival has not changed significantly in the recent decades and nephritis relapses affect over 50% of patients with lupus nephritis. Renal fibrosis affecting the tubulointerstitial compartment is a central determinant of the prognosis of any kidney disease. Notwithstanding this evidence, the current 2003 ISN/RPS classification still focuses on glomerular pathology and does not include a mandatory score with clear subcategories of the tubulointerstitial injury in the biopsy. The pathogenesis, and the morphological and molecular characteristics of this process in patients with lupus nephritis will be considered, together with a discussion about the concepts the clinician needs to efficiently address in this injury during daily practice and in future clinical trials. Both tubulointerstitial inflammation and fibrosis are strongly correlated with poor renal outcomes in lupus nephritis, regardless of the extent of glomerular damage. Therefore, it is essential to develop reliable and noninvasive approaches to predict which patients are most likely to develop CKD so that appropriate interventions can be adopted before ESRD is established. Currently, no ideal method for monitoring kidney fibrosis exists, since repeated renal biopsies are invasive. Promising methods for assessing and monitoring fibrosis non-invasively include imaging techniques, such as magnetic resonance imaging or ex vivo confocal microscopy, integrated in computational and digital pathology techniques. Finally, beyond specific immunosuppressive treatment in Lupus Nephritis, identifying and treating cardiovascular risk factors should be a cornerstone of treatment in these patients.

RESUMEN A pesar de las mejoras en la sobrevida de los pacientes y su calidad de vida, la sobrevida renal en el largo plazo no ha cambiado significativamente durante las últimas décadas, y las recidivas nefríticas afectan a más del 50% de los pacientes con nefritis lúpica. La fibrosis renal, que afecta el compartimiento tubulointersticial, es un factor determinante central en el pronóstico de todas las patologías renales. A pesar de la evidencia, la actual clasificación ISN/RPS del 2003 todavía se concentra en la patología glomerular y no incluye un score obligatorio con claras subcategorías de la lesión tubulointersticial en la biopsia. Se hablará de la patogenia y las características morfológicas y moleculares de este proceso en pacientes con nefritis lúpica, así como de los conceptos que el clínico necesita para abordar esta lesión de manera eficiente en su práctica cotidiana y en los estudios clínicos a futuro. Tanto la inflamación tubulointersticial como la fibrosis se relacionan fuertemente con desenlaces renales pobres en la nefritis lúpica, con independencia de la extensión del dañío glomerular. Resulta por lo tanto esencial desarrollar sistemas confiables y no invasivos para predecir cuáles pacientes tendrán mayor probabilidad de desarrollar enfermedad renal crónica, a fin de realizar las intervenciones apropiadas antes de que se establezca la enfermedad renal terminal (ERT). En la actualidad, no existe un método ideal para monitorear la fibrosis renal, dado que las biopsias repetidas son procedimientos invasivos. Algunos de los métodos promisorios para evaluar y monitorear la fibrosis de manera no invasiva son las técnicas de imágenes, tales como la resonancia magnética o la microscopía confocal ex vivo, integradas en técnicas de patología computarizadas y digitales. Finalmente, más allá del tratamiento inmunosupresor específico para la nefritis lúpica, identificar y tratar los factores de riesgo cardiovascular deberá ser uno de los pilares de tratamiento en estos pacientes.

Guía de práctica clínica para el tratamiento farmacológico de nefritis lúpica / Clinical practice guideline for the pharmacological treatment of lupus nephritis

La nefritis lúpica (NL) es un tipo de glomerulonefritis que se desarrolla como consecuencia del lupus eritematoso sistémico (LES), una enfermedad autoinmune sistémica de presentación clínica variable (1, 2). La NL se clasifica histológicamente en seis clases(I-VI) (3), las cuales poseen diferentes manifestaciones clínicas y expresan diferentes grados de gravedad del daño renal (1). En este documento no se abordará a pacientes con clase VI pues solo son tributarios a terapia de reemplazo renal. La NL se presenta aproximadamente en el 50 a 60% de las personas con LES, en quienes es una de las principales causas de morbimortalidad puesto que progresa a falla renal o muerte (1, 2). En suma, la prevalencia, gravedad y mortalidad de la NL son mayores en hispanos, afroamericanos, y asiáticos (4). El tratamiento farmacológico de la NL consta de las fases de inducción y mantenimiento (1). Entre los fármacos principalmente utilizados durante estas fases, se encuentran los antimaláricos, glucocorticoides (GC), inmunosupresores como micofenolato mofetilo (MMF) y ciclofosfamida (CYC) endovenosa, entre otros (1, 2). Sin embargo, la incidencia de respuesta renal completa suele ser baja (~20 a 30%) (1, 5, 6), y tanto las recaídas como los eventos adversos pueden ser frecuentes con estas terapias (1). Por ello, actualmente se ha propuesto el uso de diferentes dosis de dichos fármacos y otros inmunosupresores ya sea solos o en combinación. La evaluación de los beneficios y daños de estos fármacos permitirá conocer cuáles son las opciones más eficaces y seguras que logren inducir la remisión de la enfermedad, prevenir las recaídas, prevenir la progresión a falla renal y disminuir la mortalidad de los adultos con diagnóstico reciente de NL. Por ello, el Seguro Social de Salud (EsSalud) priorizó la realización de la presente guía de práctica clínica (GPC) para establecer lineamientos basados en evidencia con el fin de gestionar de la mejor manera los procesos y procedimientos asistenciales de la presente condición. Esta GPC fue realizada por la Dirección de Guías de Práctica Clínica, Farmacovigilancia y Tecnovigilancia del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) de EsSalud.

Non-lupus full-house nephropathy: a case series / Nefropatia "full-house" não relacionada ao lúpus: uma série de casos

Abstract Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune inflammatory disease. However, some patients may exhibit a histological pattern of kidney injury, with characteristics indistinguishable from lupus nephritis, but without presenting any extrarenal symptoms or serologies suggestive of SLE. Such involvement has recently been called non-lupus full-house nephropathy. The objective is to report a series of clinical cases referred to the Laboratory of the Federal University of Maranhão that received the diagnosis of "full-house" nephropathy unrelated to lupus, upon immunofluorescence and to discuss its evolution and outcomes. Non-lupus full-house nephropathy represents a diagnostic and therapeutic challenge, because it is a new entity, which still needs further studies and may be the initial manifestation of SLE, isolated manifestation of SLE or a new pathology unrelated to SLE.

Resumo O lúpus eritematoso sistêmico (LES) é uma doença inflamatória crônica autoimune multissistêmica. Alguns pacientes, contudo, podem exibir um padrão histológico de lesão renal, com características indistinguíveis da nefrite lúpica, porém sem apresentar quaisquer sintomas extrarrenais ou sorologias sugestivas de LES. Tal acometimento tem sido recentemente denominado nefropatia "full-house" não relacionada ao lúpus. O objetivo é relatar uma série de casos clínicos encaminhados ao Laboratório da Universidade Federal do Maranhão que receberam o diagnóstico de nefropatia "full-house" não relacionada ao lúpus à imunofluorescência e discutir sua evolução e desfechos. A nefropatia "full-house" não relacionada ao lúpus representa um desafio diagnóstico e terapêutico por ser uma entidade nova, que ainda necessita de maiores estudos e pode ser a manifestação inicial do LES, manifestação isolada do LES ou uma patologia nova não relacionada ao LES.

Utility of anti-C1q and anti-nucleosome antibodies in systemic lupus erythematosus and lupus nephritis in southwestern Colombia / Utilidad de los anticuerpos anti-C1q y anti-nucleosomas en el lupus eritematoso sistémico y la nefritis lúpica en el suroccidente colombiano

ABSTRACT Introduction: Lupus nephritis (LN) is one of the most prevalent and severe complications of systemic lupus erythematosus (SLE), requiring reliable urine and serum biomarkers to evaluate it. Anti-nucleosome and anti-C1q antibodies are associated with LN in several geographic regions. Also, southwest Colombia has a heterogeneous ethnicity, which motivated the evaluation of the frequency and relationship of such markers with LN in this region. Methods: A cross-sectional study was conducted in a health centre in south-west Colombia in 84 patients diagnosed with SLE (57 without LN; 27 with LN) between 2016 and 2018. Demographic and clinical and laboratory features, including anti-dsDNA, complement, and anti-C1q and anti-nucleosome antibodies were compared in these patients. ELISA immunoassays were performed to measure the antibodies of interest in blood samples. Statistical analysis was carried out using STATA14 software (StataCorp, College Station, Texas, USA). Quantitative variables were summarised as means or medians and compared with Mann-Whitney or Two-sample t test. Categorical variables were shown as proportions, and compared with Chi-squared or Fisher's exact test. Correlation analysis between quantitative variables was calculated using Spearman's correlation. Results: Of all 84 patients, 27 patients had LN, of which 16 (59.2%) had a positive test for anti-nucleosome antibodies and 10 (37%) for anti-C1q antibodies. An association was found between anti-C1q and proliferative forms of LN and newly diagnosed LN. A correlation was found between anti-nucleosome and anti-C1q antibodies, and anti-dsDNA and low serum complement concentrations. Conclusion: Although both markers were found in variable percentages in SLE patients and seem not to be specific markers of LN in our population, anti-C1q was associated with proliferative forms of LN and de novo LN.

RESUMEN Introducción: La nefritis lúpica (NL), una de las complicaciones más frecuentes y graves del lupus eritematoso sistémico (LES), requiere biomarcadores confiables de orina y suero para su evaluación. Los anticuerpos anti-nucleosoma y anti-C1q se asocian con la NL en varias regiones geográficas. En el suroccidente colombiano se asienta una etnia heterogénea, lo que motivó la evaluación de la frecuencia y la relación de dichos marcadores con NL en dicha región. Métodos: Realizamos un estudio transversal en un centro de salud en el suroccidente de Colombia, con 84 pacientes diagnosticados con LES (57 sin NL; 27 con NL) entre los anos 2016 y 2018. Se compararon las características demográficas, clínicas y de laboratorio, incluidos los anticuerpos anti-dsDNA, complemento, anti-C1q y anti-nucleosomas entre estos pacientes. Se realizaron inmunoensayos ELISA para medir los anticuerpos de interés en muestras de sangre. El análisis estadístico se llevó a cabo con el software Stata v.14 (Stata-Corp, College Station, Texas, EE. UU.). Las variables cuantitativas se resumieron como medias o medianas y se compararon con la prueba t de Mann-Whitney o Two-sample t test; las variables categóricas se mostraron como proporciones y se compararon con Chi-cuadrado o con la prueba exacta de Fisher. Para el análisis de correlaciones entre variables cuantitativas se calculó el coeficiente de correlación de Spearman. Resultados: Entre los 84 pacientes, 27 presentaban LN, de los cuales 16 (59,2%) tuvieron una prueba positiva para anticuerpos anti-nucleosoma y 10 (37%) para anticuerpos anti-C1q. Se encontró una asociación entre anti-C1q y formas proliferativas de NL, así como formas recientemente diagnosticadas de NL. Hubo una correlación entre los anticuerpos anti-nucleosoma y anti-C1q y el anti-dsDNA y las bajas concentraciones de complemento sérico. Conclusión: Aunque los 2 marcadores se encontraron en porcentajes variables de pacientes con LES y no parecen ser marcadores específicos de NL en nuestra población, la presencia de anti-C1q se asoció con formas proliferativas de NL y NL de novo.

Relationship of serum 25- hydroxy vitamin D and systemic lupus erythematosus / 北京大学学报(医学版)

OBJECTIVE@#To investigate the application value of serum 25-hydroxy vitamin D [25(OH)D] in systemic lupus erythematosus (SLE).@*METHODS@#Data of 158 patients with SLE in Department of Rheumatology and Immunology in the People's Hospital of Xinjiang Uygur Autonomous Region from July 2016 to July 2019. All the SLE patients were divided into two groups by SLE scores of the disease activity index (SLEADI): 59 cases of active group (SLEADI > 4), 99 cases of non-active group (SLEDAI ≤4). Fifty healthy people were selected as healthy control group. The patients' general information and their laboratory data including serum 25(OH)D levels were collected. Statistical methods used were t-test, Spearman's correalation analysis and Logistic regression analysis.@*RESULTS@#(1) A total of 208 cases were included in this study. The level of 25(OH)D in SLE group [10.4(5.6, 15.8) μg/L] was significantly lower than that in healthy control group [25.5(22.8, 32.3) μg/L, P < 0.01]. 25(OH)D level in active SLE patients [6.2(3.7, 13.8) μg/L] was significantly lower than that in remission SLE patients [12.3(7.2, 16.7) μg/L, P < 0.01]. The serum 25(OH)D level in lupus nephritis [6.7 (4.4, 12.9) μg/L] was significantly lower than that in SLE without renal involvement [13.3 (7.4, 18.7) μg/L, P < 0.01]. (2) A significant negative correlation was demonstrated between the serum level of 25(OH)D and SLEDAI (r=-0.35, P < 0.01), and the 24h urinary protein excretion (r=-0.39, P < 0.01).Positive correlation was demonstrated between the serum level of 25(OH)D and C3 that decreased (r=0.249, P < 0.05). (3) Univariate analysis showed anti- dsDNA antibodies(ds-DNA), anti-Sm antibodies(Sm), IgG, C3, C4, erythrocyte sedimentation rate (ESR), 24h urinary protein quantification(24h-pro) and 25(OH)D were associated with disease activity in the SLE patients; Multivariate Logistic regression analysis showed that 25(OH)D was associated with the disease activity of the lupus patients.@*CONCLUSION@#The decrease of vitamin D level is related to the disease activity of SLE patients, and may be related to lupus nephritis, which plays an important role in the occurrence and development of SLE.

Nefritis lúpica: experiencia con dosis reducidas de glucocorticoides en una unidad de enfermedades autoinmunes sistémicas / Lupus nephritis: low-dose glucocorticoids in a systemic autoimmune diseases unit / Nefritis lúpica: experiência con doses reduzidas de glicocorticoides em uma unidade de doenças autoinmunes sistémicas

Resumen: Introducción: las recomendaciones actuales del tratamiento de la nefritis lúpica (NL) apuntan a dosis de glucocorticoides más bajas para lograr el control de la enfermedad y evitar el daño acumulado. Objetivo: conocer y comparar la respuesta al tratamiento de pacientes con NL proliferativa en su etapa de inducción con dos pautas de tratamiento con prednisona (PDN): dosis iniciales reducidas 30 mg/d. Método: se compararon variables clínicas, analíticas y terapéuticas de pacientes con NL proliferativa categorizados en dos grupos según la dosis inicial de prednisona (PDNi) estándar o reducida. Resultados: se estudiaron 21 pacientes con NL proliferativa (n=12 PDNi reducida vs. n=9 PDNi estándar). No hubo diferencias significativas en las variables clínicas y analíticas. Se observó una diferencia estadísticamente significativa en el número de pulsos de metilprednisolona (5 ± 2,95 PDNi 30 mg/d, p = 0,041) y en la dosis de prednisona acumulada a 6 meses (12,8 mg ± 4,9 PDNi 30 mg/d, p =0,008). No hubo diferencias significativas en la proporción de pacientes que alcanzaron la respuesta completa, en el tiempo hasta alcanzarla ni en los efectos adversos entre ambos grupos. Conclusiones: el esquema terapéutico del grupo PDNi <30 mg/d se asoció a una menor dosis acumulada de prednisona y una respuesta al tratamiento comparable, lo que hace presumir menor daño acumulado relacionado al uso de glucocorticoides.

Abstract: Introduction: current recommendations to treat lupus nephritis (LN) point to low-dose glucocorticoids to control the disease and avoid cumulativedamage. Objective: to learn about and compare the response of patients with proliferative LN who are treated following two prednisone therapy guidelines: reduced initial doses 30 mg/d during the induction stage. Method: clinical, analytical and therapeutic guidelines of patients with proliferative LN were compared and classified into two groups according to the standard or low-dose initial prednisone dose. Results: 21 patients with proliferative LN were studied (n=12 low-dose initial prednisonevs. n=9 standard initial prednisone). No significant differences were found between clinical and analytical variables, although a significantly different statistic difference was observed in the number of methylprednisone pulses (5 ± 2.95 initial prednisone 30 mg/d, p = 0.041) and in the prednisone dose accumulated in 6 months (12.8 mg ± 4.9 initial prednisone 30 mg/d, p =0.008). No significant differences were seen between both groups in the proportion of patients who achieved complete response, neither in terms of the time it took to achieve it or in the side effects. Conclusions: the treatment plan for the initial prednisone <30 mg/d was associated to a lower cumulative dose of response prednisone considering the comparable treatment, what suggests there being smaller cumulative harm as a consequence of the use of glucocorticoids.

Resumo: Introdução: as recomendações atuais para o tratamento da nefrite lúpica (NL) estão orientadas a doses de glicocorticoides mais baixas para controlar a enfermidade e evitar o dano acumulado. Objetivo: conhecer e comparar a resposta ao tratamento de pacientes com NL proliferativa na etapa de indução com duas pautas de tratamento com prednisona (PDN): doses iniciais reduzidas 30 mg/d. Método: foram comparadas variáveis clínicas, analíticas e terapêuticas de pacientes com NL proliferativa divididos em dois grupos segundo a dose inicial de prednisona (PDNi) padrão ou reduzida. Resultados: 21 pacientes com NL proliferativa (n=12 PDNi reduzida vs. n=9 PDNi estândar) foram estudados. Não foram observadas diferenças significativas nas variáveis clínicas e analíticas. Observou-se uma diferença estatisticamente significativa no número de pulsos de metilprednisolona (5 ± 2,95 PDNi 30 mg/d, p = 0,041) e nas doses de prednisona acumulada aos 6 meses (12,8 mg ± 4,9 PDNi 30 mg/d, p =0,008). Não foram observadas diferenças significativas na proporção de pacientes que alcançaram a resposta completa, no tempo até alcançá-la nem nos efeitos adversos entre ambos grupos. Conclusões: o esquema terapêutico do grupo PDNi <30 mg/d foi associado a uma menor dose acumulada de prednisona em resposta ao tratamento comparável, o que sugere menos dano cumulativo relacionado ao uso de glicocorticoides.

Recent advances in the treatment of systemic lupus erythematosus with belimumab in children / 中国当代儿科杂志

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs, and lupus nephritis (LN) is the most common renal complication of SLE. Belimumab is a fully humanized monoclonal antibody that can reduce the number of B cells, thereby reducing the formation of autoantibodies. Belimumab can improve SLE response index and SLE disease activity score and delay the progression of LN in both adults and children and thus plays an important role in the treatment of SLE and LN. This article reviews related research reports of belimumab used in the treatment of children and adults with SLE in China and overseas and analyzes the efficacy and safety of belimumab in pediatric patients, in order to provide a reference for the clinical application of belimumab in children with SLE.

Identification and functional analysis of a novel phospholipase D2 gene mutation associated with familial systemic lupus erythematosus / 中南大学学报(医学版)

OBJECTIVES@#Systemic lupus erythematosus (SLE) is a kind of autoimmune inflammatory connective tissue disease which seriously endangers human health. Genetic factors play a key role in the pathogenesis of SLE. This study aims to investigate a novel phospholipase D2 (PLD2) mutation associated with familial SLE, and further explore the underlying mechanism of the mutation in SLE.@*METHODS@#The blood samples from a SLE patient, the patient's parents, and 147 normal controls were collected and DNA was extracted. Whole genome high-throughput sequencing was performed in the patient and her parents and the results were further analyzed by various bioinformatics methods. The wild type (wt), mutant type (mu), and negative control PLD2 plasmids were further constructed and transfected into 293 cells. The expression level of HRAS protein in 293 cells was detected by Western blotting.@*RESULTS@#In this SLE family, the female SLE patient and her mother, 1 in generation II and 1 in generation III had typical clinical manifestations of SLE, and all of them had lupus nephritis at early stage. The genetic characteristics are consistent with autosomal dominant inheritance. A novel PLD2 heterozygous mutation (c.2722C>T) was found in the patient and her mother, but not in her father and other normal controls. Compared with wtPLD2 plasmid and negative control PLD2 plasmid, the expression of HRAS in 293 cells transfected with muPLD2 plasmid was significantly up-regulated (both @*CONCLUSIONS@#PLD2 c.2722C>T mutation may be one of the pathogeny of SLE in this family.

Clinicopathological features of children with lupus nephritis with positive antineutrophil cytoplasmic antibody / 中国当代儿科杂志

OBJECTIVE@#To study the clinicopathological features of children with lupus nephritis (LN) with positive anti-neutrophil cytoplasmic antibody (ANCA).@*METHODS@#A retrospective analysis was performed for the children who were diagnosed with LN in the First Affiliated Hospital of Sun Yat-sen University from January 2003 to December 2019. According to the results of serum ANCA, they were divided into two groups: ANCA-positive group (@*RESULTS@#Compared with the ANCA-negative group, the ANCA-positive group had a significant reduction in leukocytes and a significant increase in erythrocyte sedimentation rate (@*CONCLUSIONS@#Children with ANCA-positive LN tend to have more severe renal pathological injury, which is not exactly parallel with clinical manifestations, suggesting that timely renal biopsy is of great importance.