TCM Treatment of Podocyte Injury in IgA Nephropathy Based on Multiple TCM Theories： A Review / 中国实验方剂学杂志

IgA nephropathy is the most common primary glomerular disease in China. Its clinical manifestations are mainly proteinuria， hematuria， hypertension， edema， hyperuricemia， etc. Most patients have hidden onset. 30%-40% of patients develop into end stage renal disease 10-20 years after diagnosis and rely on dialysis or kidney transplantation to maintain their lives， which is extremely harmful. Proteinuria is a common clinical manifestation of this disease， and most patients have small-to-moderate amounts of proteinuria， while 10%-24% of patients have large amounts of proteinuria. Proteinuria is the main risk factor affecting the progression of renal function in IgA nephropathy. Podocytes are the terminal part of the glomerular filtration barrier， and various factors can affect the fusion and detachment of podocyte processes that occur after podocyte injury. They are common histological lesions in IgA nephropathy and are key factors leading to proteinuria and the continuous progression of the disease. At present， Western medicine lacks targeted treatment for podocyte injury， with limited intervention methods. Drugs such as glucocorticoids are often used for treatment， and there are many adverse reactions. Based on the physiological function of podocytes， pathological and physiological changes after injury， and histological morphology of this disease， it is believed that it is closely related to traditional Chinese medicine's "Xuanfu Theory" "Kidney Collateral Syndrome" "Collateral Disease Theory"， and "Dry Blood Theory". More and more studies have shown that traditional Chinese medicine， which has the characteristics of multiple links， pathways， and targets， has a significant therapeutic effect on podocyte injury in IgA nephropathy. It can protect podocytes and reduce proteinuria and has good application and research prospects. This article systematically summarizes the mechanism and morphological changes of podocyte injury in IgA nephropathy， the understanding of podocyte injury in traditional Chinese medicine theory， and the research progress in traditional Chinese medicine treatment of podocyte injury in IgA nephropathy， so as to provide a reference for further research and application of traditional Chinese medicine intervention in podocyte injury in IgA nephropathy.

Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy / 中国药房

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

Vasculitis por IgA del adulto. Caso clínico

La vasculitis por IgA, es la vasculitis más frecuente en pediatría. Puede presentarse en adultos, con una clínica y evolución diferente y un pronóstico más grave que en los niños, incluida la progresión a enfermedad renal terminal. La historia natural de la enfermedad y de la nefritis, ha sido poco estudiada en adultos; no se dispone de criterios diagnósticos universalmente aceptados y el tratamiento es controvertido, dada la ausencia de estudios controlados, randomizados que lo avalen. Se reporta el caso de un paciente que presentó un síndrome purpúrico petequial, microhematuria, proteinuria y una evolución rápida a la insuficiencia renal, de cuyo estudio etiológico surge el diagnóstico de vasculitis por IgA del adulto.

The IgA vasculitis is the most common vasculitis in Pediatrics. It can also present in adults but with a different clinical course and a worse prognosis, including the possibility of progression to end stage renal disease. The natural history of the disease and its nephritis have been scarcely studied in adults. There is no universal agreement in diagnostic criteria and the treatment is controversial given the absence of controlled randomized trials. We report the case of a patient who presented clinically with a petechial purpuric rash, microhematuria, proteinuria and rapid progression to renal failure that was diagnosed with IgA vasculitis in adult.

A vasculite por IgA é a vasculite mais comum em pediatria. Pode ocorrer em adultos, com apresentação e evolução clínica diferentes e prognóstico mais grave do que em crianças, incluindo progressão para doença renal terminal. A história natural da doença e da nefrite tem sido pouco estudada em adultos; Não existem critérios diagnósticos universalmente aceitos e o tratamento é controverso, dada a ausência de estudos controlados e randomizados que o apoiem. É relatado o caso de um paciente que apresentou síndrome purpúrica petequial, microhematúria, proteinúria e rápida evolução para insuficiência renal, de cujo estudo etiológico surge o diagnóstico de vasculite por IgA do adulto.

Prevalence of IgA anti-tissue transglutaminase antibody in a cohort of iranians patients with inflammatory bowel disease

Background and Aims: Some studies have reported the coexistence of inflammatory bowel disease (IBD) and celiac disease (CD). However, the prevalence of anti-tissue transglutaminase antibodies (IgA and IgG) and their screening value in patients with IBD is not yet clear. This study aimed to assess the prevalence of IgA anti-tTG and its potential correlation with disease status in patients with IBD. Materials and Methods: This cross-sectional study was conducted on 110 patients with confirmed IBD diagnosis at Ghaem Hospital, Mashhad, Iran. For each patient, all demographic and clinical data including age, extra intestinal manifestations, underlying diseases, types of diseases, and surgical history were collected. IgA anti-tissue transglutaminase titers were assessed by enzyme-linked immunosorbent assay. Results: None of the patients with IBD were positive for IgA anti-tTG antibodies, with a mean titer of 3.31 ± 1.3 AU/mL. Also, the mean titers were not associated with age, gender and various disease clinical features including the disease history, underlying disease, diagnosis type, extraintestinal manifestations, and surgery history. Conclusion: No significant prevalence pattern of IgA anti-tTG antibody was observed in patients with IBD. Accordingly, serological screening for CeD is not recommended in IBD patients, unless in a relevant clinical CeD suspicion. (AU)

IgA deficiente / IgA deficiency

El déficit selectivo de IgA se define como la ausencia parcial o total de IgA en el suero, con cifras normales en el resto de las inmunoglobulinas. Se presentó una paciente femenina de 1 año y 7 meses, de padres no consanguíneos, con antecedentes familiares negativos para enfermedades genéticas o defectos congénitos, e IgA deficiente. Los estudios inmunológicos mostraron un gran déficit de IgA, de ahí que el diagnóstico se definió como una inmunodeficiencia congénita, por déficit selectiva de IgA o inmunodeficiencia variable común (trastorno genético producto de una herencia monogénica); para lo cual se le realiza una cuantificación de la subclase de IgG y así determinar si es una mutación en un mismo gen defectuoso. La paciente evolucionó satisfactoriamente con los tratamientos recibidos; los valores de IgA permanecieron nulos, no siendo así con el resto de las inmunoglobulinas.

Selective IgA deficiency is defined as the partial or total absence of IgA in the serum, but normal levels in the rest of the immunoglobulins. We present a female patient aged 1 year and 7 months, of non-consanguineous parents, who had a negative family pathological history for genetic diseases or congenital defects and IgA deficiency. Immunological studies showed a high IgA deficiency, hence the diagnosis was defined as congenital immunodeficiency due to selective IgA deficiency or common variable immunodeficiency (genetic disorder resulting from monogenic inheritance); a quantification of the IgG subclass was also performed in order to determine if it was a mutation in the same defective gene. The patient evolved satisfactorily with the treatments received; the IgA values remained null, but this was not the case with the rest of the immunoglobulins.

Immunological and bacteriological monitoring of periodontal tissue in pregnancy

We determine periodontal pathogens in periodontal pockets from pregnant women with periodontitis and associate it to the C reactive protein (CRP), nitrates, immunoglobulin A and G (Ig A and G), and myeloperoxidase (MPO) levels in saliva to identify some biomarkers as tools to predict the periodontal status from pregnant. The samples were obtained from periodontal pockets and saliva from 100 pregnant women (PW) and 50 non-pregnant women (NPW). Every patient was evaluated by: 1) probing depth (PD) and loss of clinical attachment level (CAL); 2) in saliva; CRP, MPO, Ig A and G) and nitrite concentrations, 3) in periodontal pockets: P.gingivalis, T.forsythia, T.denticola, P.intermedia, A.actinomycetemcomitans. InfoStat/P 2008 software was used with a p-value <0.05. Clinical parameters showed stages I and II of PD in both groups. P.intermedia and A.actinomycetemcomitans were observed only in periodontal pockets from PW. The CAL was higher in pregnant of the 3rd trimester than in the other stages and was associated with low levels of IgA and the presence of P.intermedia and T. forsythia in the same trimester. The levels of IgA in saliva would reflect the immunological situation in pregnant women. This could be used to monitor the immune status of the gingival tissues during pregnancy.

Determinamos patógenos periodontales en bolsas periodontales de gestantes con periodontitis y lo asociamos a los niveles de proteína C reactiva (PCR), nitratos, inmunoglobulina A y G (Ig A y G) y mieloperoxidasa (MPO) en saliva para identificar biomarcadores como herramientas para predecir el estado periodontal de la gestante. Las muestras se obtuvieron de bolsas periodontales y saliva de 100 mujeres embarazadas (ME) y 50 mujeres no embarazadas (NoE). Cada paciente fue evaluado por: 1) profundidad de sondaje(PD) y pérdida del nivel de inserción clínica (NIC); 2) en saliva; PCR, MPO, Ig A y G y concentraciones de nitritos, 3) en bolsas periodontales: P.gingivalis, T.forsythia, T.denticola, P.intermedia, A.actinomycetemcomitans. Se utilizó el software InfoStat/P 2008 con un valor de p<0,05. Los parámetros clínicos mostraron estadios I y II de EP en ambos grupos. P.intermedia y A.actinomycetemcomitans se observaron solo en bolsas periodontales de ME. El NIC fue mayor en gestantes del 3er trimestre que en las demás etapas y se asoció con niveles bajos de IgA y presencia de P.intermedia y T.forsythia en el mismo trimestre. Los niveles de IgA en saliva reflejarían la situación inmunológica en la mujer embarazada. Esto podría usarse para monitorear el estado inmunológico de los tejidos gingivales durante el embarazo.

Crescentic IgA nephropathy following SARS-CoV-2 vaccination. Report of a case / Nefropatía por IgA extracapilar luego de la vacunación contra el SARS-CoV-2. Reporte de un caso

ABSTRACT Introduction: Studies have shown that the frequency of acute kidney injury (AKI) increases in patients with COVID-19. Acute tubular necrosis has been reported to be the most common damage in these patients, probably due to impaired renal perfusion. On the other hand, different complex pathophysiological processes may be involved due to viral infection's direct effects on the renin-angiotensin-aldosterone system, the activation of coagulopathy, the cytokine storm, and the activation of the immune system. Many glomerular diseases may be seen in these patients, like anca-associated vasculitis, membranous glomerulonephritis, and IgA nephropathy. Clinical case: We present a newly diagnosed crescentic IgA nephropathy (IgAN) case after a SARS-CoV-2 infection and vaccination. A 31-year-old man with no medical history presented with gross hematuria 24 hours after SARS-CoV-2 infection. Hematuria regressed spontaneously within three days. He was vaccinated with two doses of CoronaVac (Sinovac) three months after he had been infected by SARS-CoV-2. Then he was vaccinated with the Pfizer-BioNTech COVID-19 vaccine one month after the second dose of CoronaVac (Sinovac) vaccine. He presented with gross hematuria and subnephrotic proteinuria 24 hours after the first dose of the Pfizer-BioNTech COVID-19 vaccine. A kidney biopsy was performed and showed crescentic IgA nephropathy (IgAN). He was started on methylprednisolone and angiotensin receptor blocker. Patients who receive mRNA-based vaccines demonstrate robust antibody production against the receptor-binding domain (RBD) of the S1 protein. Similar to natural infection, due to the intense stimulation of immune response from mRNA-based vaccines compared to other vaccines, the patients may produce de novo antibodies, leading to IgA-containing immune-complex deposits. Conclusions: This case highlights the immunological effects of the novel mRNA-based SARS-CoV-2 vaccines. Nephrologists should be aware of new-onset hematuria or proteinuria after SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccine.

RESUMEN Introducción: Los estudios han demostrado que la frecuencia de insuficiencia renal aguda (IRA) aumenta en pacientes con COVID-19. Se ha informado que la necrosis tubular aguda es el daño más común en estos pacientes, probablemente debido a la alteración de la perfusión renal. Por otro lado, pueden estar involucrados diferentes procesos fisiopatológicos complejos, debido a los efectos directos de la infección viral sobre el sistema renina-angiotensina-aldosterona, la activación de la coagulopatía, la tormenta de citoquinas y la activación del sistema inmunológico. En estos pacientes se pueden observar muchas enfermedades glomerulares, como vasculitis asociada a anca, glomerulonefritis membranosa y nefropatía por IgA. Caso clínico: Presentamos un caso de nefropatía IgA extracapilar (NIgA) de nuevo diagnóstico tras una infección por SARS-CoV-2 y vacunación. Un hombre de 31 años sin antecedentes médicos presentó hematuria macroscópica 24 horas después de la infección por SARS-CoV-2. La hematuria remitió espontáneamente en 3 días. Fue vacunado con dos dosis de CoronaVac (Sinovac) tres meses después de haber sido infectado por el SARS-CoV-2. Luego fue vacunado con la vacuna Pfizer-BioNTech COVID-19, un mes después de la segunda dosis de la vacuna CoronaVac (Sinovac). Presentó hematuria macroscópica y proteinuria no nefrótica 24 horas después de la primera dosis de la vacuna Pfizer-BioNTech COVID-19. Se realizó una biopsia renal que mostró NIgA extracapilar. Comenzó con metilprednisolona y bloqueador del receptor de angiotensina. Los pacientes que reciben vacunas basadas en ARNm demuestran anticuerpos contra el dominio de unión al receptor (RBD) de la proteína S1. De manera similar a la infección natural, debido a la fuerte estimulación de la respuesta inmunitaria de las vacunas basadas en ARNm en comparación con otras vacunas, los pacientes pueden producir anticuerpos de novo, lo que lleva a depósitos de complejos inmunitarios que contienen IgA. Conclusiones: Este caso destaca los efectos inmunológicos de las nuevas vacunas contra el SARS-CoV-2 basadas en ARNm. Los nefrólogos deben estar al tanto de la aparición de hematuria o proteinuria luego de la infección por SARS-CoV-2 o la vacuna contra el SARS CoV-2 basada en ARNm.

Nefropatía por IgA en una adolescente con lupus eritematoso sistémico juvenil. Reporte de caso

Introducción: El lupus eritematoso sistémico juvenil (LESJ) es una enfermedad autoinmunitaria, multisistémica, caracterizada por la producción de autoanticuerpos y el desarrollo frecuente de glomerulonefritis mediada por inmunocomplejos. La nefritis lúpica es una complicación frecuente y grave del LESJ, con alta morbilidad, siendo causa de insuficiencia renal terminal en muchos de estos pacientes. La nefropatía por IgA representa la etiología más común en la población general y raramente se asocia con LESJ. Caso clínico: adolescente femenino con LESJ en quien se diagnosticó nefritis no lúpica (nefropatía por IgA). Conclusiones: El diagnóstico anatomopatológico es clave para establecer el pronóstico y planificar el tratamiento.

Introduction: Juvenile systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease characterized by the production of autoantibodies and the frequent development of immune complex-mediated glomerulonephritis. Lupus nephritis is a frequent and serious complication of JSLE, has a high associated morbidity rate, and is the cause of end-stage renal failure in many of these patients. IgA Nephropathy represents the most common etiology in the general population and is rarely associated with JSLE. Clinical case: a female adolescent with JSLE who was diagnosed with non-lupus nephritis (IgA nephropathy). Conclusions: The anatomopathological diagnosis is key to establish the prognosis and plan the treatment.

Gastrointestinal tract involvement in patients with potential celiac disease beyond the small intestine: An early proof with IgA anti-tissue transglutaminase-2 antibody deposits

Background: IgA anti-tissue transglutaminase-2 antibody (anti-TG2Ab) deposits in intestinal and extraintestinal organs have been used to link the respective pathological changes in these organs with celiac disease (CeD). Aims: To know if parts of intestine other than the duodenum, such as esophagus, stomach, and colon, have any pathology related to potential CeD or have mucosal IgA anti-TG2 Ab deposits. Settings and Design: A prospective case–control study conducted from April 2018 to December 2019. Materials and Methods: Nine patients with potential CeD and 27 age- and gender-matched patients with irritable bowel syndrome were recruited as cases and controls, respectively. Mucosal biopsies were collected from esophagus, stomach, duodenum, and rectosigmoid regions, histological changes were evaluated, and IgA anti-TG2 Ab deposits were analyzed in these regions by two-color immunohistochemical staining. Statistics: Data were analyzed using statistical software Stata 14.0. Results: No distinct difference in mucosal lymphocytosis were identified between biopsies of patients with potential CeD and controls at the following sites: esophagus (11.1% vs 0%, P = 0.079), stomach (14.3% vs 7.7%, P = 0.590), and rectum (20% vs 0%, P = 0.067). Co-localized IgA anti-TG2Ab deposits were observed more in potential CeD than in controls at esophagus 22.2% (2/9) vs 0%, P = 0.012; stomach 66.7% (6/9) vs 11.5% (3/26), P < 0.001; and duodenum 66.7% (6/9) vs 0%, P < 0.001 but not at rectum 0% (0/4) vs 0% (0/25). Conclusion: Although histological changes are not distinct, a subset of subjects with potential CeD has pan-intestinal involvement other than in the duodenum.

Warm Autoimmune Haemolytic Anaemia due to IgA and IgG � A Rare Clinical Scenario

Autoimmune Haemolytic Anaemia (AIHA) is a decompensated acquired haemolysis caused by the host immune system producing autoantibodies that bind to the antigens on the surface of circulating erythrocytes, leading to haemolysis and decreased red cell survival. It requires efficient and advanced immunohaematological and transfusion support. Despite advances in medical field, simple test like Direct Antiglobulin Test (DAT) still remains the diagnostic hallmark. The sensitive column gel technology further helps to characterise these antibodies according to class, subclass and titre of antibodies. It is very important to characterize these autoantibodies as there is a relation between strength of DAT and in vivo haemolysis. Serologically, cases are divided into warm (mainly due to IgG), cold (mainly due to IgM) or mixed depending upon the thermal amplitude of the antibody. IgA and IgG antibodies causing warm type of AIHA are rare as monospecific gel cards are not available in all centres. We here report rare case series of warm AIHA caused by dual antibodies IgA and IgG.

Celiaquía: Aprovechar el poder diagnóstico de los anticuerpos

La celiaquía es un trastorno mediado por la respuesta inmune al gluten ingerido en individuos genéticamente susceptibles. La enfermedad celíaca afecta al 1 % de la población mundial, y su incidencia se ha incrementado sustancialmente en las últimas décadas. Sin embargo, aún la enfermedad celíaca es pobremente reconocida por la comunidad médica y por la población, tanto a nivel internacional, como nacional, muchos casos permanecen subdiagnosticados. Para mejorar el diagnóstico y manejo del paciente celíaco se recomienda el uso oportuno de la serología específica de la enfermedad celíaca. De los distintos anticuerpos asociados con la enfermedad celíaca, los anticuerpos anti-transglutaminasa tisular (anti-TGt IgA) representan la primera opción diagnóstica por su elevada sensibilidad y especificidad. La prueba de anti-TGt IgA no solo permite descartar de modo confiable la celiaquía, sino funciona como filtro para la selección de pacientes tributarios de biopsia intestinal para la confirmación diagnóstica. El desarrollo de la serología ha posibilitado la aplicación de nuevas estrategias diagnósticas que obvian la biopsia intestinal al menos en algunos grupos de pacientes.

Celiac disease is a disorder mediated by the immune response to ingested gluten in genetically susceptible individuals. Celiac disease affects 1% of the world population, and its incidence has increased substantially in recent decades. However, celiac disease is still poorly recognized by the medical community and by the population, both domestic and international, many cases remain underdiagnosed. Improving the diagnosis and management of the celiac patient, the timely use of specific serology for celiac disease is recommended. Different antibodies associated with celiac disease, however, anti-tissue transglutaminase antibodies (anti-TGt IgA) represent the first diagnostic option due to their high sensitivity and specificity. The anti-TGt IgA test not only constantly rules out celiac disease, but also functions as a filter for the selection of patients eligible for intestinal biopsy for diagnostic confirmation. The development of serology has enabled the use of new diagnostic strategies that avoid intestinal biopsy, at least in some groups of patients.

Research progress on tumor immunosuppressive functions of immunoglobulin A and its clinical significance / 中国肿瘤生物治疗杂志

@#[摘 要] 免疫球蛋白A（IgA）是最常见抗体之一，并在黏膜表面提供第一道免疫保护。IgA+ B细胞是IgA产生的主要来源细胞。近年来的研究表明，IgA在肿瘤发生发展中呈现双向作用，在不同的肿瘤类型及免疫微环境中发挥不同的作用，尤其是IgA+ B细胞和IgA的促肿瘤和免疫抑制作用成为目前关注的热点及研究的难点。肿瘤微环境（TME）中IgA+ B细胞可通过分泌免疫抑制因子，如IL-10、TGF-β、PD-L1、FASL、IL-35和Tim1发挥免疫抑制作用。免疫抑制性IgA在多种肿瘤组织中高表达，并与恶性肿瘤预后差密切相关。本文总结了IgA+ B细胞和IgA的免疫抑制和促肿瘤作用及其机制，讨论了肿瘤免疫抑制微环境中细胞因子和代谢产物等在调控IgA类转换重组（CSR）中所起的作用，以及IgA免疫抑制作用的临床意义，为肿瘤免疫治疗提供新的思路和治疗策略。

Notoginsenoside R_1 interferes with renal oxidative stress and Nrf2/HO-1 signaling pathway to alleviate kidney injury in mice with IgA nephropathy and its mechanism / 中国中药杂志

The purpose of this study was to investigate the effect of notoginsenoside R_1(NGR_1) on alleviating kidney injury by regulating renal oxidative stress and the Nrf2/HO-1 signaling pathway in mice with IgA nephropathy(IgAN) and its mechanism. The mouse model of IgAN was established using a variety of techniques, including continuous bovine serum albumin(BSA) gavage, subcutaneous injections of carbon tetrachloride(CCl_4) castor oil, and tail vein injections of lipopolysaccharide(LPS). After successful modeling, mice with IgAN were randomly separated into a model group, low, medium, and high-dose NGR_1 groups, and a losartan group, and C57BL6 mice were utilized as normal controls. The model and normal groups were given phosphate buffered saline(PBS) by gavage, the NGR_1 groups were given varying dosages of NGR_1 by gavage, and the losartan group was given losartan by gavage for 4 weeks. The 24-hour urine of mice was collected after the last administration, and serum and kidney tissues of mice were taken at the end of the animal experiment. Then urine red blood cell count(URBCC), 24-hour urine protein(24 h protein), serum creatinine(Scr), and blood urea nitrogen(BUN) levels were measured. The enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of galactose-deficient IgA1(Gd-IgA1), kidney injury molecule 1(Kim-1), and neutropil gelatinase-associated lipocalin(NGAL) in the mouse serum. The assay kits were used to detect the levels of malondialdehyde(MDA) and superoxide dismutase(SOD), and immunofluorescence(IF) was used to detect the expression level of glutathione peroxidase 4(GPX4) in the mesangial region. Western blot was used to detect the protein expression of nuclear transcription factor E2 related factor 2(Nrf2)/heme oxygenase 1(HO-1) signaling pathway in the renal tissue. Hematoxylin-eosin(HE) staining was used to observe pathological alterations in the glomerulus of mice. The results revealed that, as compared with the model group, the serum Gd-IgA1 level, URBCC, 24 h protein level, renal damage markers(Kim-1 and NGAL) in the high-dose NGR_1 group decreased obviously and renal function indicators(BUN, Scr) improved significantly. The activity of SOD activity and expression level of GPX4 increased significantly in the high-dose NGR_1 group, whereas the expression level of MDA reduced and protein expression levels of Nrf2 and HO-1 increased. Simultaneously, HE staining of the renal tissue indicated that glomerular damage was greatly decreased in the high-dose NGR_1 group. In conclusion, this study has clarified that NGR_1 may alleviate the kidney injury of mice with IgAN by activating the Nrf2/HO-1 signaling pathway, improving antioxidant capacity, and reducing the level of renal oxidative stress.

Severe bilateral visual loss as the first sign of IgA nephropathy / Perda visual bilateral grave como o primeiro sinal da nefropatia por IgA

ABSTRACT We describe a case of a 33-years-old woman who presents with severe acute bilateral visual loss secondary to massive exudative hypertensive maculopathy as the first sign of immunoglobulin A nephropathy. The patient's ophthalmic examination showed bilateral cotton-wool spots, flame-shaped retinal hemorrhages, diffuse narrow arterioles, optic disk edema, and exudative maculopathy. Systemic workup demonstrated a systolic and diastolic blood pressure of 240 mmHg and 160 mmHg, respectively, proteinuria, and hematuria, suggesting kidney disease as the causative condition. A kidney biopsy confirmed immunoglobulin A nephropathy. She was treated with systemic corticosteroids, antihypertensive drugs, and a single bilateral intravitreal injection of aflibercept. There was a prompt resolution of macular edema and vision improvement. Our case draws attention to the fact that severe bilateral visual loss can be the first sign of severe hypertension. Secondary causes, such as immunoglobulin A nephropathy, should be ruled out.

RESUMO Nosso objetivo é descrever uma paciente de 33 anos de idade, com perda visual bilateral grave por maculopatia hipertensiva exsudativa como o primeiro sinal da nefropatia por imunoglobulina A. A fundoscopia revelou a presença de manchas algodonosas, hemorragias em chama-de-vela, estreitamento arteriolar difuso, edema de disco óptico e maculopatia exsudativa bilateral. A pressão arterial sistólica foi de 240mmHg e a diastólica de 160 mmHg associado a proteinúria e hematúria, sugerindo a presença de doença renal. A biópsia renal confirmou a nefropatia por imunoglobulina A. A paciente foi tratada como corticoide sistêmico, drogas anti-hipertensivas e uma única dose intravítrea de Aflibercept em ambos os olhos. Houve rápida melhora do edema macular e da acuidade visual. Nosso caso chama a atenção para o fato de que a perda visual bilateral grave pode ser a primeira apresentação de uma doença hipertensiva sistêmica. Causas secundárias como a nefropatia por imunoglobulina A devem ser afastadas.

Bushen Jianpi Jiedu Liyan Formula Regulates Homing-associated Cell Adhesion Molecules in Rat Model of IgA Nephropathy / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Bushen Jianpi Jiedu Liyan formula on the expression of integrin alpha 4 beta 1 （α4 β1）， vascular cell adhesion molecule-1 （VCAM-1）， stromal-derived factor-1 （SDF-1）， and chemokine receptor-4 （CXCR4） in the small intestine and bone marrow of the rat model of immunoglobulin A（IgA） nephropathy. MethodA total of 120 male SD rats were used to establish the IgA nephropathy model by intragastric administration of bovine serum albumin （BSA）， subcutaneous injection of CCl4， and tail vein injection of lipopolysaccharide （LPS）. The successfully modeled rats were randomized into blank， model， lotensin （63 mg·kg-1）， and low-， medium-， and high-dose （10.4， 20.81， 41.62 g·kg-1， respectively） Bushen Jianpi Jiedu Liyan formula groups （n=16）. The rats were treated with corresponding drugs according to their body weight. After 7 weeks of administration， the rats were sacrificed for the collection of samples， and the protein and mRNA levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the small intestine and bone marrow were determined by immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed increased red blood cell count in the urine at the 10th， 12th， 14th， 16th weeks （P<0.01）， and such increases were reduced in the drug intervention groups （P<0.05）， especially in the medium-dose Bushen Jianpi Jiedu Liyan formula group （P<0.05）. Compared with those in the blank group， the protein levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria in the model group were up-regulated （P<0.05）， and such un-regulations were inhibited in the drug intervention groups （P<0.05）. Compared with the model group， medium-dose Bushen Jianpi Jiedu Liyan formula down-regulated the protein levels of SDF-1 and CXCR4 in the intestinal lamina propria （P<0.05）. Compared with the blank group， the model group showed down-regulated mRNA levels of α4 β1 and SDF-1 and up-regulated mRNA levels of VCAM-1 and CXCR4 （P<0.05）. Compared with the model group， the drug intervention groups showed down-regulated mRNA levels of SDF-1 and CXCR4 （P<0.05）. ConclusionBushen Jianpi Jiedu Liyan formula regulates the expression of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria to inhibit the homing effect of plasma cells， which may be associated with the Toll-like receptor-mediated activation of immune response. Bushen Jianpi Jiedu Liyan formula can down-regulate the expression of adhesion molecules to inhibit the proliferation of plasmocytes in circulation， so as to reduce the renal injury of IgA nephropathy.

Effect of Dahuang Xiezhuo Prescription on Renal Tubular Function in Patients with IgA Nephropathy Complicated with Hyperuricemia / 中国实验方剂学杂志

ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the clinical symptoms， blood uric acid， and renal tubular function of patients with immunoglobulin A （IgA） nephropathy in stages 1-2 of chronic kidney disease （CKD） complicated with hyperuricemia （HUA）. MethodSixty patients with IgA nephropathy in stages 1-2 of CKD complicated with HUA of spleen and kidney deficiency and combined turbidity and blood stasis syndromes were randomly divided into an observation group and a control group， with 30 cases in each group. The patients in the control group received basic treatment， i.e.， losartan potassium tablets 50-100 mg/time， once per day， and sodium bicarbonate tablets 0.5 g/time， three times per day by oral administration， combined with low-salt， low-fat， and low-purine diet. The patients in the observation group received Dahuang Xiezhuo prescription on the basis of basic treatment， one dose per day， twice a day in the morning and evening with warm water. Both groups were treated for two months. The total scores of traditional Chinese medicine（TCM）syndrome， blood pressure， 24 h urinary protein （24 h UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr） ［glomerular filtration rate （eGFR） was calculated by CKD-epidemiology collaboration （CKD-EPI） formula］， serum uric acid （SUA）， and renal tubular function indexes ［urinary α1-microglobulin （α1-MG）， urinary β2-microglobulin （β2-MG）， urinary kidney injury molecule-1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL）］ of the two groups before treatment and two months after treatment were recorded. The clinical efficacy of the two groups was evaluated two months after treatment. ResultAfter 2 months of treatment，the total effective rate in the observation group was 81.48%（22/27），higher than 50.00%（14/28） in the control group（χ2 =6.661，P<0.05）. The total scores of TCM syndrome， 24 h UTP， and SUA in the observation group and the observation group were lower than those before treatment （P<0.05）， and compared with the control group after treatment， the observation group decreased more significantly （P<0.05）. After treatment， the blood pressure in the observation group and the observation group was lower than that before treatment （P<0.05）， and there was no significant difference in blood pressure between the two groups after treatment. After treatment， the levels of urinary α1-MG， β2-MG， KIM-1， and NGAL in the two groups were lower than those before treatment （P<0.05）， and the observation group was lower than the control group after treatment （P<0.05）. There were no significant inter-group and intra-group differences in BUN， SCr， and eGFR levels before and after treatment. There were no obvious abnormalities in blood routine， liver function， and electrolytes before and after treatment in the two groups， and no adverse reactions such as allergies occurred. ConclusionDahuang Xiezhuo prescription can effectively improve the clinical symptoms of IgA nephropathy with HUA （CKD1-2） patients with spleen and kidney deficiency and combined turbidity and blood stasis syndromes， reduce blood uric acid level， alleviate renal tubular injury， and protect the kidney. The curative effect is better than that of basic treatment.

Subcorneal pustular dermatosis type of IgA Pemphigus in a 35-year-old female: A case report

Introduction@#IgA pemphigus is a rare, distinct variant of Pemphigus characterized by vesiculopustular eruptions mediated by IgA autoantibodies targeting keratinocyte cell surface antigens, desmocollins 1-3 and sometimes desmogleins 1 and 3. Its classical features have been described in literature but atypical cases have also been documented. This report presents such case posing a diagnostic dilemma.@*Case Report@#A 35-year-old female presented with a 16-year history of intermittent eruptions of multiple hyperpigmented, annular and circinate, desquamating plaques and coalescing flaccid pustules on erythematous bases on the scalp, neck, trunk, and extremities. Histopathologic examination revealed subcorneal pustular dermatitis, and direct immunofluorescence was positive for granular intercellular IgG and IgA deposits in the epidermis. Antinuclear antibody test was negative and C3 level was normal. Antibody tests against desmogleins 1 and 3 were both negative. Topical potent corticosteroid therapy resulted in complete resolution of all lesions in three weeks.@*Conclusion@#Diagnostic dilemmas arise when laboratory results do not correlate with clinical findings. Findings of IgA autoantibodies in patients with pemphigus-like skin eruptions led to the diagnosis of subcorneal pustular dermatosis type of IgA pemphigus. Dapsone is the treatment of choice although topical potent corticosteroid alone may provide complete remission in some cases, avoiding the potential adverse effects of systemic therapy

Stability of human immunoglobulin(pH 4) for intravenous injection after process optimization / 中国生物制品学杂志

@#Objective To evaluate the stability of human immunoglobulin(pH 4)for intravenous injection(IGIV)after process optimization.Methods A filter plate and B filter membrane were used to filter the protein components in different separation stages to reduce the residue of immunoglobulin A(IgA)in the product in multi-batch large-scale production. The finished product was examined for the physical properties(appearance,visible foreign body,insoluble particle examination and thermal stability test)and the chemical properties[protein content,purity,molecular size distribution,titers of antiHBs,diphtheria antibody,prokallikrein activator(PKA),anti-complement activity(ACA),anti-A and anti-B hemagglutinin,and IgA residue]. The accelerated and long-term stability tests were performed.Results There was no significant difference in the key quality indicators between IGIV batches produced by the optimized process and the normal process,while the IgA residue decreased significantly(t = 3. 992 and 11. 215 respectively,each P < 0. 05). In the accelerated stability and long-term stability tests,all the test results of IGIV after process optimization were qualified,which met the relevant regulations in the third part of Chinese Pharmacopoeia(2020 edition).Conclusion IGIV after process optimization can effectively reduce IgA residue with good stability,which is of great significance for blood product manufacturers to improve the quality of IGIV products.

Expression optimization and preliminary identification of recombinant monoclonal antibody IgA against SARS-CoV-2 / 中国生物制品学杂志

@#Objective To prepare monoclonal antibody IgA against severe acute respiratory syndrome coronavirus 2(SARSCoV-2),optimize relevant expression conditions to increase the expression level,and preliminarily explore the effect of IgA antibody on anti-SARS-CoV-2.Methods The plasmid encoding IgAl-F61 antibody sequence was mixed with polyethyleneimine(PEI) transfection reagent and then transfected into EXPi293F~(TM) cells to transiently express antibody protein;The optimal culture conditions and expression levels of monomeric IgAl(mIgAl)-F61 and dimeric IgAl(dIgAl)-F61 in EXPi293F~(TM) cells were determined by optimizing the ratio of heavy chain(Hc),light chain(Lc) and joining chain(Jc),the proportion of plasmid and PEI,and the harvest time after transfection.The supernatant after transfection was purified by affinity chromatography,and then determined for the concentration by BCA,analyzed for the expression integrity and purity of antibody by SDS-PAGE and size exclusion chromatography-high performance liquid chromatography(SEC-HPLC),and detected for the neutralizing activity of antibody by pseudovirus neutralization assay.Results The optimal expression level of mIgAl-F61 was 123.45 μg/mL and the purity of purified antibody was over 95% when the ratio of Hc to Lc was 1:2,the ratio of plasmid to PEI was 1:3,and the supernatant was harvested 5 d after transfection;The highest purity of dIgAlF61 was more than 90% when the ratio of Hc:Lc:Jc was 1:2:1.The results of pseudovirus neutrali-zation assay against Omicron BA.4/5 showed that dIgAl-F61 exhibited better neutralizing activity than IgG-F61,and the value of half maximum inhibitory concentration(IC_(50)) was reduced by about 4 times.Conclusion Recombinant monoclonal antibodies mIgAl-F61 and dIgAl-F61 against SARS-CoV-2 were successfully expressed with high purity and dIgAl showed better neutralizing activity than IgG in vitro.

Expression optimization and preliminary identification of recombinant monoclonal antibody IgA against SARS-CoV-2 / 中国生物制品学杂志

@#Objective To prepare monoclonal antibody IgA against severe acute respiratory syndrome coronavirus 2(SARSCoV-2),optimize relevant expression conditions to increase the expression level,and preliminarily explore the effect of IgA antibody on anti-SARS-CoV-2.Methods The plasmid encoding IgAl-F61 antibody sequence was mixed with polyethyleneimine(PEI) transfection reagent and then transfected into EXPi293F~(TM) cells to transiently express antibody protein;The optimal culture conditions and expression levels of monomeric IgAl(mIgAl)-F61 and dimeric IgAl(dIgAl)-F61 in EXPi293F~(TM) cells were determined by optimizing the ratio of heavy chain(Hc),light chain(Lc) and joining chain(Jc),the proportion of plasmid and PEI,and the harvest time after transfection.The supernatant after transfection was purified by affinity chromatography,and then determined for the concentration by BCA,analyzed for the expression integrity and purity of antibody by SDS-PAGE and size exclusion chromatography-high performance liquid chromatography(SEC-HPLC),and detected for the neutralizing activity of antibody by pseudovirus neutralization assay.Results The optimal expression level of mIgAl-F61 was 123.45 μg/mL and the purity of purified antibody was over 95% when the ratio of Hc to Lc was 1:2,the ratio of plasmid to PEI was 1:3,and the supernatant was harvested 5 d after transfection;The highest purity of dIgAlF61 was more than 90% when the ratio of Hc:Lc:Jc was 1:2:1.The results of pseudovirus neutrali-zation assay against Omicron BA.4/5 showed that dIgAl-F61 exhibited better neutralizing activity than IgG-F61,and the value of half maximum inhibitory concentration(IC_(50)) was reduced by about 4 times.Conclusion Recombinant monoclonal antibodies mIgAl-F61 and dIgAl-F61 against SARS-CoV-2 were successfully expressed with high purity and dIgAl showed better neutralizing activity than IgG in vitro.