IgA nephropathy in systemic lupus erythematosus patients: case report and literature review

Silva, Leonardo Sales da; Almeida, Bruna Laiza Fontes; Melo, Ana Karla Guedes de; Brito, D.C.S.E.; Braz, Alessandra de Sousa; Freire, Eutília Andrade Medeiros

doi:10.1016/j.rbre.2014.10.011

Cited by 15 publications

(10 citation statements)

References 13 publications

(19 reference statements)

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“…In our series of men with SLE, clinically significant renal involvement was present in 11/18 patients (61.1%) and proliferative nephropathies were the most prevalent histological type (7/11, 63.6%). Of particular interest is the presence of significant mesangial IgA deposits in two of the LN patients that is in accordance with the literature data of the possibility for development if IgA nephritis in SLE [9]. Three of our patients had history of diabetes.…”

Section: Discussionsupporting

confidence: 90%

Systemic Lupus in males – clinical-laboratory, immunological and histological characteristics.

Kundurdjiev

Nikolova

Kostadinova

et al. 2022

RBJ

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Systemic lupus erythematosus is a chronic, systemic, non-organ-specific autoimmune disease that affects all organs and systems of the human body and is characterized by the production of autoantibodies against nuclear antigens. Its prevalence in Europe reaches 1:2500. It affects mostly women (female : male ratio=9 : 1) in fertile age group (15-45 years). The clinical course of lupus in males is characterized by more aggressive clinical course and the development of serious complications, such as vasculitis, central nervous system involvement, antiphospholipid syndrome, etc. For the period of 7 years (2012-2019) we observed overall 18 male patients with systemic lupus, 11 with biopsy-proven renal involvement and 7 without clinically significant renal disease (proteinuria < 0.5 g/24 h., no erythrocyturia/cylindruria, normal renal function), mean age at the diagnosis 39.6 +/- 12.3 years. All patients received pathogenetic treatment (corticosteroids + cytotoxic agents). Three had secondary antiphospholipid syndrome, 1 – inflammatory bowel disease, 1 – seronegative spondyloarthropathy. Three had type 2 diabetes. The authors discuss the clinical, immunological and histological characteristics and the therapeutic approach in males with systemic lupus.

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Section: Discussionsupporting

confidence: 90%

Systemic Lupus in males – clinical-laboratory, immunological and histological characteristics.

Kundurdjiev

Nikolova

Kostadinova

et al. 2022

RBJ

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“…Although the co-association of SLE and IgAN had been reported in several human patients, the possibility that IgA deposition might be a subtype or even a primary trigger of kidney pathology in human SLE had not been considered until a patient diagnosed with SLE was found to contain glomerular IgA deposits. 10 The ABIN1[D485N] mice also accumulate glomerular IgA deposits. 4 Since IgAN and SLE are both relatively common conditions, it is possible that their co-existence is underdiagnosed.…”

Section: Resultsmentioning

confidence: 99%

Prevention and partial reversion of the lupus phenotype in ABIN1[D485N] mice by an IRAK4 inhibitor

Petrova

Nanda

Scudamore³

et al. 2021

Lupus Sci Med

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ObjectiveWe have reported previously that the IRAK4 inhibitor PF06426779 given to ubiquitin-binding-defective ABIN1[D485N] mice at 6 weeks of age prevents the major facets of lupus that develop 10 weeks later. The present study was undertaken to investigate whether PF06426779 could reverse the lupus phenotype when administered to 13-week-old ABIN1[D485N] mice that had already developed symptoms of lupus.MethodsSplenomegaly, the number of splenic neutrophils, TFH and Germinal Centre B (GCB) cells, serum levels of immunoglobulins, the extent of kidney, liver and lung pathology, and glomerular IgA and IgM were measured after feeding 13-week-old ABIN1[D485N] and wild-type mice for another 10 weeks with R&M3 diet with and without PF06426779 (4 g/kg).ResultsFollowing drug treatment, spleen size and weight, splenic neutrophil numbers, and serum IgA and glomerular IgA levels of ABIN1[D485N] mice returned to those seen in wild-type mice. The rise in splenic TFH and GCB numbers, the increase in kidney and liver pathology, and the concentrations of serum IgG1, IgG2A and IgE between 13 and 23 weeks were suppressed. There was no reduction in the level of anti-self double-stranded DNA, anti-self nuclear antigens or IgM during the drug treatment.ConclusionsThe results demonstrate the therapeutic potential of IRAK4 inhibitors for the treatment of lupus and raise the possibility of monitoring efficacy by measuring decreases in the serum levels of IgA. Our results support the view that there may be a closer connection between lupus and IgA nephropathy than realised previously.

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“…More importantly, we report that not only both IgA1 and IgA2 subtypes levels are higher in the fecal samples of SLE patients, but also IgA antibodies in general, and IgA1 in particular, have significantly higher nAg reactivity compared to that of HCs. Although it is not clear if higher fecal IgA or its nAg reactivity have any role in the systemic autoimmunity of SLE patients, IgA nephropathy has been reported in a subset of SLE patients [34]. Furthermore, circulating IgA+ plasma cells with mucosal phenotype have been detected in human SLE [35].…”

Section: Discussionmentioning

confidence: 99%

Fecal immunoglobulin A (IgA) and its subclasses in systemic lupus erythematosus patients are nuclear antigen reactive and this feature correlates with gut permeability marker levels

Gudi

Kamen

Vasu

2022

Preprint

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Objective: Systemic lupus erythematosus (SLE) is characterized by the production of anti-nuclear autoantibodies. Our preclinical studies showed a correlation between pro-inflammatory features of the gut mucosa and autoimmune progression in lupus. The current study was aimed at comparing stool samples of SLE patients and healthy controls (HC) for the gut permeability and inflammatory markers, and the abundance and nAg reactivity of immunoglobulin A (IgA) and its subclasses. Methods: The abundance of gut inflammation and permeability markers, Calprotectin and Zonulin, and IgA and IgA subclasses (IgA1 and IgA2) in cross-sectional stool samples from 21 SLE patients and 21 HC subjects were determined by quantitative ELISA. The nuclear-antigen (nAg) reactivities of fecal IgA and IgA-subclasses were determined by employing dsDNA and nucleohistone (NH) specific ELISA. Results: The abundances of Zonulin, total IgA, and IgA1- and IgA2- subclasses were observed to be significantly higher in the fecal samples of SLE patients compared to HCs. SLE patients also showed higher nAg reactivity titers of fecal IgA, IgA1 and IgA2. Importantly, dsDNA- and NH- reactive fecal IgA1:IgA2 ratios were higher in SLE patients. Furthermore, the abundance and nAg reactivity of fecal IgA, IgA1 particularly, showed strong correlation with the fecal Zonulin levels in SLE patients. Conclusion: Higher amounts of gut permeability protein and nAg-reactive IgA are produced in the intestine, likely in the proximal gut as indicated by the IgA1:IgA2 ratio, in SLE patients. These features of SLE patients, and perhaps at-risk subjects, could serve as biomarkers of systemic autoimmune activity. However, additional studies using longitudinal samples from first degree relatives are needed.

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IgA nephropathy in systemic lupus erythematosus patients: case report and literature review

Cited by 15 publications

References 13 publications

Systemic Lupus in males – clinical-laboratory, immunological and histological characteristics.

Systemic Lupus in males – clinical-laboratory, immunological and histological characteristics.

Prevention and partial reversion of the lupus phenotype in ABIN1[D485N] mice by an IRAK4 inhibitor

Fecal immunoglobulin A (IgA) and its subclasses in systemic lupus erythematosus patients are nuclear antigen reactive and this feature correlates with gut permeability marker levels

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