Local Renal Autoantibody Production in Lupus Nephritis

Espéli, Marion; Bökers, Susanne; Giannico, Giovanna A.; Dickinson, Harriet; Bardsley, Victoria; Fogo, Agnes B.; Smith, Kenneth G. C.

doi:10.1681/asn.2010050515

Cited by 130 publications

(105 citation statements)

References 54 publications

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“…Because BXSB also had B cells in the glomerulus, the BXSB genomic background rather than the Yaa mutation might have a role in the infiltration of B cells in the glomerulus. Studies on lupus models have demonstrated that infiltrating B cells in the kidney secrete antibodies with various antigen specificities, contributing to increased in situ immune complexes [29]. Recent reports have suggested that depleting B cells either before or after disease onset prevented and/or delayed the onset of nephritis in several different lupus model mice [30,31].…”

Section: Discussionmentioning

confidence: 99%

Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models

Kimura¹,

Ichii²,

Otsuka³

et al. 2013

Am J Nephrol

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Background: Membranous proliferative glomerulonephritis (MPGN) is a major primary cause of chronic kidney disease (CKD). Podocyte injury is crucial in the pathogenesis of glomerular disease with proteinuria, leading to CKD. To assess podocyte injuries in MPGN, the pathological features of spontaneous murine models were analyzed. Methods: The autoimmune-prone mice strains BXSB/MpJ-Yaa and B6.MRL-(D1Mit202-D1Mit403) were used as the MPGN models, and BXSB/MpJ-Yaa⁺ and C57BL/6 were used as the respective controls. In addition to clinical parameters and glomerular histopathology, the protein and mRNA levels of podocyte functional markers were evaluated as indices for podocyte injuries. The relation between MPGN pathology and podocyte injuries was analyzed by statistical correlation. Results: Both models developed MPGN with albuminuria and elevated serum anti-double-strand DNA (dsDNA) antibody levels. BXSB/MpJ-Yaa and B6.MRL showed severe proliferative lesions with T and B cell infiltrations and membranous lesions with T cell infiltrations, respectively. Foot process effacement and microvillus-like structure formation were observed ultrastructurally in the podocytes of both MPGN models. Furthermore, both MPGN models showed a decrease in immune-positive areas of nephrin, podocin and synaptopodin in the glomerulus, and in the mRNA expression of Nphs1, Nphs2, Synpo, Actn4, Cd2ap, and Podxl in the isolated glomerulus. Significant negative correlations were detected between serum anti-dsDNA antibody levels and glomerular Nphs1 expression, and between urinary albumin-to-creatinine ratio and glomerular expression of Nphs1, Synpo, Actn4, Cd2ap, or Podxl.Conclusion: MPGN models clearly developed podocyte injuries characterized by the decreased expression of podocyte functional markers with altered morphology. These data emphasized the importance of regulation of podocyte injuries in MPGN.

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Section: Discussionmentioning

confidence: 99%

Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models

Kimura¹,

Ichii²,

Otsuka³

et al. 2013

Am J Nephrol

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“…71 Such B cells undergo intrarenal proliferation and activation, which contributes to local inflammation and tissue pathology in addition to their role for systemic and intrarenal autoantibody production. 26,72,73 These data provide a rationale for B celltargeted therapies in LN. 74,75 T cell infiltrates also contribute to immunopathology in LN, particularly IL-17 producing CD3 + /CD4 + or CD3 + CD4/8 2/2 T cells.…”

Section: Intrarenal Pathogenic Mechanisms Of Lnmentioning

confidence: 93%

The Pathogenesis of Lupus Nephritis

Lech¹,

Anders

2013

Journal of the American Society of Nephrology

382

295

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Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-a signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies.

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Section: Role In Gnmentioning

confidence: 99%

“…These are often organized along with T cells and DCs into lymph node-like structures that are known as tertiary lymphoid tissues (151,153,154). B lymphocytes within these structures are actively dividing (supported by local BAFF and APRIL), are undergoing somatic hypermutation, and sometimes form germinal centers (151,(153)(154)(155). The presence of germinal centers is strongly associated with tubular basement membrane immune complexes, providing a highly plausible link between local B-lymphocyte activation and progression of lupus nephritis in humans (151,153,154).…”

Section: Role In Gnmentioning

confidence: 99%

B Cells, Antibodies, and More

Hoffman¹,

Lakkis

Chalasani

2016

Clinical Journal of the American Society of Nephrology

364

268

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B cells play a central role in the immunopathogenesis of glomerulonephritides and transplant rejection. B cells secrete antibodies that contribute to tissue injury via multiple mechanisms. In addition, B cells contribute to disease pathogenesis in autoimmunity and alloimmunity by presenting antigens as well as providing costimulation and cytokines to T cells. B cells also play an immunomodulatory role in regulating the immune response by secreting cytokines that inhibit disease onset and/or progression. B cell-targeted approaches for treating immune diseases of the kidney and other organs have gained significant momentum. However, much remains to be understood about B-cell biology in order to determine the timing, duration, and context of optimal therapeutic response to B cell-targeted approaches. In this review, we discuss the multifaceted roles of B cells as enhancers and regulators of immunity with relevance to kidney disease and transplantation.

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Local Renal Autoantibody Production in Lupus Nephritis

Cited by 130 publications

References 54 publications

Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models

Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models

The Pathogenesis of Lupus Nephritis

B Cells, Antibodies, and More

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