Phenotypic and functional alterations of peritoneal macrophages in lupus-prone mice.

BACKGROUND: Several studies have demonstrated the contribution of innate immune cells, including macrophages, in promoting systemic lupus erythematosus (SLE). Macrophages, one of the most abundant cell populations in the peritoneal cavity, are considered multifunctional cells with phenotypic plasticity. However, the functional properties of peritoneal macrophages in steady-state and during the progression of SLE remain poorly defined. METHODS AND RESULTS: Using the [NZB × NZW]F1 (BWF1) murine model of SLE, we analyzed the phenotype and function of peritoneal macrophages during the disease's onset. We found a higher frequency of peritoneal macrophages and B1a cells in BWF1-diseased mice than age-matched controls. Additionally, macrophages from diseased animals expressed lower levels of CD206, MHC-II, and Sirpα. RNAseq analysis identified 286 differentially expressed genes in peritoneal macrophages from diseased-BWF1 mice compared to control mice. Functional experiments demonstrate that peritoneal macrophages from diseased-BWF1 mice secrete higher levels of pro-inflammatory cytokines when activated with TLR7 and TLR9 agonists, and they were less efficient in suppressing the activation and proliferation of peritoneal LPS-activated B cells. These data demonstrate that peritoneal macrophages from BWF1-diseased mice present phenotypic and functional alterations shifting to a more pro-inflammatory state. CONCLUSIONS: The increase of macrophages with an altered phenotype and function together with the accumulation of B1a cells in the peritoneal cavity of diseased-BWF1 mice may promote the progression of the disease. Advancing awareness of the role and phenotype of peritoneal macrophages in SLE may contribute to a better understanding of these types of diseases and the development of novel therapies.

Choroidopathy and optic neuropathy in systemic lupus erythematosus, a case report.

Although the associated ocular pathology to systemic lupus erythematosus is not infrequent, its manifestations and importance can be overlooked by rheumatologists and ophthalmologists. We present the case of a 44-year-old male with a history of systemic lupus erythematosus whose disease started with metamorphopsia and subjective alteration of the visual fields of both eyes, with a marked decrease in visual acuity, secondary to bilateral serous retinal detachment and optic neuropathy. He received systemic corticosteroids, biological therapy and posterior subtenon triamcinolone acetonide injections, showing an improvement in visual acuity. Ophthalmic manifestations should be considered a sign of systemic lupus erythematosus activity, therefore the treatment is essentially systemic, in combinationed with local coadjutant treatment.

Global excellence in rheumatology in Latin America: The case of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) affects more severely non-White populations, due to their genetic background and sociodemographic characteristics. Several studies have evaluated Latin American SLE patients to determine their genetic and clinical characteristics as well as prognostic factors; these studies have not only allowed the development of treatment guidelines aimed at the region but also to support regional and global projects. Additionally, educational activities in Spanish and Portuguese have been started to reduce our patients' health illiteracy. Despite the relatively low research output from Latin American countries, we consider that studies from our region coupled with the networks developed to increase our capabilities, could be a model for other rare autoimmune diseases.

Alopecia areata y vitamina D sérica en pacientes iraquíes: un estudio de casos y controles / Alopecia Areata And Serum Vitamin D in Iraqi Patients: a case-control study

Background: Alopecia areata (AA) is a typical hair issue, which may have obliterating mental and social outcomes and is portrayed by the nearness of nonscarring alopecia. Objective: This examination has targets to assess the serum nutrient D levels , with AA; contrast the outcome and clearly sound control; and confirm relationship between AA types and serum nutrient D levels. Patients Also Methods: the examine might have been led clinched alongside Tikrit educating healing facility throughout those time starting with June 2019 of the limit for January 2020. Irrefutably the quantity of subjects associated with the assessment was ninety individuals isolated in two social events; the patients bundle were forty five the people who whimper of AA while the resulting gathering including a forty five age and sex-made solid volunteers were picked as a benchmark gathering. The degree and movement of the alopecia were noted and the patients were meticulously broke down for signs of various ailments. Research center assessments were led to patients and also to those control population, these included serum vitamin D levels were measured as 25-hydroxyvitamin D {25(OH)D} using a chemiluminescence microparticle immunoassay. Blood models were gotten starting with patients and control subjects after totally taught consent was gotten. Results : An essential complexity may have been found for serum 25-OH Vit D levels between patients other than controls. Vitamin D sufficiency were more common in controls than in patients. Serum Vitamin D was deficient in both cases and controls group; but, the deficiency was significantly more throughout AA group (35. 6%) compared to the handle group (11. 1%). Among the list patients gathering, levels associated with nutrient D were totally higher in guys in contrast with females. Conclusions: AA might be related with nutrient D deficiency as mean degrees of nutrient D of patients were seen as fundamentally lower than typical sound controls.

Circulating exosomal micrornas as biomarkers of systemic lupus erythematosus

OBJECTIVES: Many studies indicate that microRNAs (miRNAs) could be potential biomarkers for various diseases. The purpose of this study was to investigate the clinical value of serum exosomal miRNAs in systemic lupus erythematosus (SLE). METHODS: Serum exosomes were isolated from 38 patients with SLE and 18 healthy controls (HCs). The expression of miR-21, miR-146a and miR-155 within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using receiver operating characteristic (ROC) curves, we evaluated the diagnostic value of exosomal miRNAs. RESULTS: Exosomal miR-21 and miR-155 were upregulated (p<0.01), whereas miR-146a expression (p<0.05) was downregulated in patients with SLE, compared to that in HCs. The expression of miR-21 (p<0.01) and miR-155 (p<0.05) was higher in SLE patients with lupus nephritis (LN) than in those without LN (non-LN). The analysis of ROC curves revealed that the expression of miR-21 and miR-155 showed a potential diagnostic value for LN. Furthermore, miR-21 (R=0.44, p<0.05) and miR-155 (R=0.33, p<0.05) were positively correlated with proteinuria. The expression of miR-21 was negatively associated with anti-SSA/Ro antibodies (R=−0.38, p<0.05), and that of miR-146a was negatively associated with anti-dsDNA antibodies (R=−0.39, p<0.05). CONCLUSIONS: These findings suggested that exosomal miR-21 and miR-155 expression levels may serve as potential biomarkers for the diagnosis of SLE and LN.

Risk factors for cytomegalovirus disease in systemic lupus erythematosus (SLE): a systematic review

Abstract Background: Cytomegalovirus (CMV) is an opportunistic pathogen causing reactivation and disease in Systemic Lupus Erythematosus (SLE) patients. This study aims to systematically review the literature for risk factors associated with CMV disease in SLE patients, in order to identify those more susceptible to CMV infection during their treatment. Methods: A systematic review was conducted on 4 different search engines and via hand search until May 2017. Studies were included after quality assessment via the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields (HTA KMET). Results: Two studies on CMV disease were included. Elevated CMV viral load, higher steroid doses, use of immunosuppressants and disease duration were the most commonly associated risk factors for CMV disease. Conclusion: High CMV viral loads, longer SLE disease duration and higher steroid doses were associated with CMV disease. Further studies studying the risk of treatment drugs and role of interventions in the development of CMV infection are needed.

Definition of NPSLE: Does the ACR Nomenclature Still Hold?

Systemic lupus erythematosus (SLE) patients have frequently neuropsychiatric manifestations. From the first description of coma in 1875, a variety of manifestations has been described to occur in SLE. However, the lack of standardization reduced the comparability of published studies. In 1999, the American College of Rheumatology published guidelines to define neuropsychiatric nomenclature in SLE. This was the first step toward uniform diagnostic criteria. Several studies have been published since then applying the ACR criteria and frequencies of different manifestations can now be compared between cohorts. Although these criteria are diagnostic, therapeutic approach to different manifestations varies according to nature and severity of the manifestations. Herby, we will review the different definition for NPSLE published, and determine advantages and limitation.

Glomerulopatía colapsante en lupus eritematoso sistémico con respuesta positiva a tratamiento con mofetil micofenolato / Collapsing Glomerulopathy in systemic lupus erythematosus with positive response to the treatment with mycophenolate mofetil

La glomerulonefritis colapsante es una enfermedad poco frecuente que puede estar asociada a distintas causas, una de ellas son las enfermedades autoinmunes y dentro de estas el lupus eritematoso sistémico (LES). De manera frecuente se presenta con un cuadro de severas alteraciones renales que tienden a progresar la enfermedad renal terminal, con escasa respuesta a los tratamientos. Se presenta un caso de glomerulonefritis colapsante asociado a lupus eritematoso sistémico que tuvo una respuesta completa al tratamiento de inducción con la combinación de glucocorticoides, antimaláricos y mofetil micofenolato iniciado precozmente por el diagnóstico temprano realizado por biopsia renal(AU)

Collapsing glomerulonefritis is a slightly frequent disease that can be associated to different causes. Autoimmune diseases are part of those, and inside these, the systemic lupus erythematosus (SLE). It frequently appears with manifestations of severe renal alterations that tend to develop the renal terminal disease, with scanty response to the treatments. It is presented a case of collapsing glomerulonefritis associated to systemic lupus erythematosus that had a complete response to the treatment of induction with the combination of glucocorticoids, antimalarials and mycophenolate mofetil used prematurely after the early diagnosis performed by renal biopsy(AU)

Células dendríticas e interferones en el lupus eritematoso sistémico / Dendritic cells and interferons in systemic lupus erythematosus

Resumen El lupus eritematoso sistémico (LES) es un trastorno autoinmune con base genética, caracterizado por la aparición de autoanticuerpos, formación y depósito de complejos inmunes circulantes e inflamación crónica en varios órganos. La etiología es multifactorial y, en individuos genéticamente predispuestos, factores medioambientales y componentes hormonales juegan un rol clave en el sistema inmune de esta enfermedad. Cerca de 25 loci genéticos han sido identificados, indicando la importancia en esta enfermedad; sin embargo, la tasa de concordancia para el LES es de tan solo el 25% entre gemelos monocigotos (1,2). Un ejemplo de ello son las deficiencias de los componentes iniciales en la vía clásica del complemento sérico como el C1q, C2 o C4, que si bien es infrecuente, confieren susceptibilidad genética para el LES en una tasa del 30% en caso de deficiencia del C4 y de más del 90% para una deficiencia del C1q (3). Por otro lado, se demostró que el C1q inhibe a las células dendríticas plasmocitoides (CDP) en la secreción de interferón alfa (IFN-a), proporcionando así un nuevo enlace entre la deficiencia del complemento y la activación de la vía del IFN (4). Por ello, el IFN-a es considerado como un actor central en la patogénesis del LES, encontrándose concentraciones séricas altas en los brotes de esta enfermedad (5). En consecuencia, estos IFN ejercen efectos claves en la fisiopatología del LES, lo que sugiere que esta citoquina no solo posee un efecto a nivel del sistema inmune innato, sino también en las respuestas inmunes adaptativas. Teniendo en cuenta estos hechos, se puede anticipar que las CDP, fuente principal de secreción de IFN, están involucradas en dicha enfermedad autoinmune. En esta revisión nos centraremos en la participación de las CDP y del IFN en el LES (6,7).

Abstract Systemic Lupus Erythematosus (SLE) is an autoimmune disorder with a genetic basis, and is characterised by the appearance of autoantibodies, the formation and deposition of circulating immune complexes, and chronic inflammation in various organs. It is of multifactorial origin, and in genetically predisposed individuals, environmental factors and hormonal components play a key role in the immune system of the disease. About 25 genetic loci have been identified, indicating the importance in this pathology. However, the concordance rate for SLE is only 25% among monozygotic twins. An example of this is the deficiencies of the initial components in the classical serum complement pathway such as C1q, C2 or C4, which, although rare, confer genetic susceptibility for SLE at a rate of 30% in the case of C4 deficiency, and more than 90% for C1q deficiency. It was also demonstrated that C1q inhibits plasmacytoid dendritic cells (pDCs) in the secretion of interferon-alpha (IFN-a), thus providing a new link between complement deficiency and activation of the IFN pathway. Therefore, IFN-a is considered to have a central role in the pathogenesis of SLE, with high serum concentrations being found in outbreaks of this disease. These IFN exert prominent immunoregulatory effects, suggesting that this cytokine is key, not only in the innate immune system, but also in adaptive immune responses. Taking these facts into account, it can be anticipated that pDCs, the main source of IFN secretion, are involved in this autoimmune disease. In this review, we will focus on the participation of pDCs and IFNs in SLE.

Clinical, serologic, and immunogenetic characterization (HLA-DRB1) of late-onset lupus erythematosus in a Colombian population.

INTRODUCTION: Late-onset systemic lupus erythematosus (SLE) represents a specific subgroup that is defined as onset after 50 years of age. Late-onset lupus may have a different clinical course and serological findings, which may delay diagnosis and timely treatment. OBJECTIVES: The objective of this paper is to determine the clinical, serologic, and immunogenetic differences among Colombian patients with late-onset SLE versus conventional SLE patients. METHODOLOGY: This was a cross-sectional study in a Colombian population. Patients and their medical records were analyzed from the services of Rheumatology in Bogotá and met the criteria for SLE, according to the American College of Rheumatology (ACR) revised criteria for the classification of SLE.In a reference group of late-onset SLE patients (98 participants, with an onset after 50 years of age) and a group of conventional SLE patients (72 participants, with an onset of age of 49 years or less), multiple clinical variables (age, clinical criteria for lupus, alopecia, weight loss, fever, Raynaud's phenomenon) and multiple serological variables (blood count, blood chemistry profile, autoantibodies) were analyzed. Additionally, the HLA class II (DRB1) of all the patients was genotyped, including an additional group of patients without the autoimmune disease. Statistical analysis was performed using the STATA 10.0 package. RESULTS: In the group of late-onset lupus, there was a higher frequency of pleurisy (p = 0.002), pericarditis (p = 0.026), dry symptoms (p = 0.029), lymphopenia (p = 0.007), and higher titers of rheumatoid factor (p = 0.001) compared with the group of conventional SLE. Late-onset SLE patients had a lower seizure frequency (p = 0.019), weight loss (p = 0.009), alopecia (p < 0.001), and Raynaud's phenomenon (p = 0.013) compared to the conventional SLE group. In late-onset SLE, HLA DR17 (DR3) was found more frequently compared with individuals without autoimmune disease (OR 3.81, 95% CI 1.47 to 10.59) (p = 0.0016). CONCLUSION: In the Colombian SLE population analyzed, there may be a probable association of several clinical and serologic variants, which would allow the differentiation of variables in the presentation of the disease among patients with late-onset SLE vs. conventional SLE.

Late onset systemic lupus erythematosus with severe hypercalcaemia / Lupus eritematoso sistémico de inicio tardío con hipercalcemia severa

We report a case of a 76-year old female presenting with symptomatic severe hypercalcaemia, and subsequently diagnosed with late onset SLE due to the presence of anaemia, leucopenia, antibodies of antinuclear (ANA), anti-dsDNA, and also kidney impairment. Serum levels of FGF23 and intact-parathyroid hormone (iPTH) were low in this patient. Serum calcium, FGF23 and iPTH levels responded to steroids, which occurred simultaneously with disease activity. On follow-up, the faster increase in FGF23 than in parathyroid hormone suggested that FGF23 might be involved in the pathogenesis of hypercalcaemia in SLE.

Se reporta el caso de una mujer de 76 años de edad que se presentó con hipercalcemia sintomática severa, y a la que posteriormente le fuera diagnosticada LES de inicio tardío con presencia de anemia, leucopenia, anticuerpos antinucleares (ANA), anti-dsDNA, e insuficiencia del riñón. Los niveles séricos del factor de crecimiento fibroblástico 23 (FGF23) y la hormona paratiroidea intacta (iPTH) fueron bajos en este paciente. Los niveles de calcio séricos, FGF23 e iPTH respondieron a los esteroides, que ocurrieron simultáneamente con la actividad de la enfermedad. En el seguimiento, el hecho de que el factor FGF23 aumentara más rápidamente que la hormona paratiroidea, sugiere que el FGF23 podría estar involucrado en la patogénesis de la hipercalcemia en LES.

The role of CD55/CD59 complement regulatory proteins on peripheral blood cells of systemic lupus erythematosus patients / O papel das proteínas reguladoras do complemento CD55/CD59 em células de sangue periférico de pacientes com lúpus eritematoso sistêmico

CD55 e CD59 são proteínas de membrana ancoradas por glicosilfosfatidilinositol que apresentam propriedades reguladoras da ativação da cascata do complemento. Essa regulação ocorre através da inibição da C3 convertase pelo CD55 e prevenção da etapa final de polimerização do complexo de ataque à membrana pelo CD59. Deficiência na expressão dessas proteínas pode estar associada a uma maior ativação do sistema complemento, inclusive do complexo de ataque à membrana, levando à morte celular. Pacientes com lúpus eritematoso sistêmico, com anemia hemolítica e linfopenia, parecem apresentar uma deficiência adquirida de CD55 e CD59. Contudo, os mecanismos que modulam essa diminuída expressão continuam desconhecidos e o seu impacto nas manifestações do lúpus eritematoso sistêmico precisa ser mais bem estudado.

CD55 and CD59 are glycosylphosphatidylinositol-anchored proteins with regulatory properties on the activating cascades of the complement system. This regulation occurs through inhibition of the C3-convertase formation by CD55, and prevention of the terminal polymerization of the membrane attack complex by CD59. Deficiency in the expression of these proteins can be associated with increased susceptibility to complement-mediated cell death. Systemic lupus erythematosus patients with hemolytic anemia and lymphopenia seem to have an acquired deficiency of CD55 and CD59 proteins. However, the mechanisms involved in this deficiency and its impact on the clinical manifestation of SLE needs to be further investigated.

Características clínicas y serológicas de los pacientes con LES de inicio tardío en una población colombiana / Clinical and serological characteristic of late onset SLE patients in a Colombian population

El Lupus Eritematoso Sistémico (LES) puede afectar todas las edades y su inicio en los mayores de 50 años aunque es poco común no es raro, correspondiendo aproximadamente a un 12% de los pacientes. Se han reportado diferencias en la forma de presentación del LES de inicio tardío y variaciones con respecto al de los pacientes jóvenes relacionadas con el género, el intervalo entre el inicio de síntomas y el momento del diagnóstico, las diferentes manifestaciones clínicas, el perfil inmunológico y su severidad y pronóstico. Objetivo: el objetivo fue describir las características clínicas y serológicas de los pacientes con LES del anciano (> 50 años) y compararlas con una población control de pacientes de inicio temprano (> 18 años y < 50 años) tanto al inicio de la enfermedad como durante su evolución. Métodos: se realizó un estudio retrospectivo en la Sección de Reumatología de la Universidad de Antioquia en el Hospital Universitario San Vicente de Paul, en Medellín, Colombia que incluyó 21 pacientes con LES de inicio tardío (15 mujeres y 6 hombres) y 63 pacientes con LES de inicio temprano (57 mujeres y 6 hombres) que cumplieran con cuatro o más criterios del ACR para el diagnóstico de LES. Las historias clínicas de todos los pacientes se revisaron exhaustivamente en busca de características epidemiológicas de la enfermedad, manifestaciones clínicas divididas por sistemas, perfil de autoanticuerpos y pruebas de función renal, hematológicas y endocrino-metabólicas. Además se evaluaron los índices de actividad de la enfermedad según el SLEDAI. Resultados: la relación mujer-hombre fue significativamente más baja en la población de inicio tardío (2,5:1 vs. 9,5:1; p = 0,005). Comparados con los jóvenes los ancianos tuvieron frecuencias más altas de mialgias (47,6 vs. 25,4%, p= 0,05), neumonitis intersticial (19 vs. 1,6%, p= 0,003), trastornos del afecto (19 vs. 4,8%; p= 0,04) y osteoporosis (23,8 vs. 1,6%, p= 0,0006) entre otros. Por el contrario los jóvenes tuvieron mayor frecuencia de eritema malar (49,2 vs. 23,85%, p= 0,004), úlceras orales (44,4 vs. 0%, p= 0,0001) y nefritis lúpica (39,7 vs. 14,3%, p= 0,032) en el inicio de la enfermedad. Durante el seguimiento persistieron estos hallazgos. En la evaluación de autoinmunidad sólo se encontró diferencia estadísticamente significante en la disminución en el seguimiento de C3 (45% vs. 71,6 con p= 0,03) y C4 (36,8% vs. 64,1% con p= 0,04) en los pacientes jóvenes. La actividad de la enfermedad evaluada por el índice de SLEDAI no mostró diferencias entre ambos grupos, tanto al inicio como durante el seguimiento de la enfermedad. Conclusión: en esta población colombiana existen importantes diferencias clínicas entre ambos grupos que pueden afectar el pronóstico.

Systemic lupus erythematosus (SLE) affects all ages and the onset of SLE above 50 years of age is uncommon but not rare and up 12% of patients are affect after the 6th decade. It has been reported differences in the form of presentation of late onset SLE and variations between young and older patients such as sex predominance, interval between time of onset of symptoms and signs to diagnosis, clinical and immunological features, severity and prognosis. Objective: the aim of this study were to describe and compare retrospectively the clinical and serological features between early (> 18 and < 50 years) and late onset (> 50 years) SLE in a Colombian population. Methods: twenty one patients with late onset SLE (15 women and 6 men) and 63 patients with early SLE (57 women and 6 men) were studied retrospectively. All met four or more ACR criteria for the diagnosis of SLE. A detailed clinical and laboratory assessment according to a pre-established protocol was made of each patient including age, sex, age at onset and diagnosis, number of ACR criteria, clinical manifestations, immunological markers, index of activity illness with SLEDAI and years of follow up. Results: late onset SLE female/male ratio was much reduced than in the early group (2,5:1 vs. 9.5:1, p= 0.005) and more frequencies of myalgias (47.6 vs. 25.4% p= 0.05), interstitial pneumonitis (19.0% vs. 1.6%, p= 0.003), mood disorders (19 vs. 4.8%, p= 0.04), osteoporosis (23.8% vs. 1,6%, p= 0.0006) instead of early SLE who had more malar rash (49.2% vs. 23.85, p= 0.04), oral ulcers (44.4% vs. 0%, p= 0.0001), nephritis (39.7% vs. 14.3% p= 0.032) at the onset of the disease. This features persisted during the follow up. We did not find any differences in activity illness with SLEDAI. Conclusion: in this Colombian population there are important clinical differences between groups, which can affect the prognosis of SLE.