Abstract
Introduction. Dysfunction of the B lymphocyte is considered to be involved in the pathogenesis of lupus nephritis (LN). Intrarenal B cells have been found in several forms of inflammatory kidney disease. B-cell activating factor (BAFF) regulates B lymphocyte proliferation and survival, and contributes to human autoimmune disease. Their role in renal inflammation is not well defined. Methods. Clinical parameters and renal biopsies from 62 LN patients were prospectively analyzed. We performed standard immunohistochemistry on serial paraffin tissue sections using monoclonal antibodies to CD20 and BAFF to investigate the characteristics and significance of locally infiltrating B cells and local BAFF expression in patients with LN. Results. Intrarenal B cells and/or BAFF were mainly distributed in the renal interstitium. Compared to the LN-non-B-cell/BAFF expression group, proteinuria (g/24 hour), blood urea nitrogen, serum creatinine levels, LN renal activity, and chronicity indices, were all significantly greater in the LN-B-cell/BAFF expression groups. The expression of BAFF was strongly associated with the quantity of B-cell infiltrate in the interstitium. Conclusion. As BAFF expression was strongly associated with B-cell infiltration, we hypothesize that altered B-cell differentiation and tolerance induced by excess BAFF may be central to the pathogenesis of LN.
Highlights
Dysfunction of the B lymphocyte is considered to be involved in the pathogenesis of lupus nephritis (LN)
The following demographic, clinical, and serologic data were collected at the time of renal biopsy: sex; age; duration of systemic lupus erythematosus (SLE) and LN; Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); levels of proteinuria, blood urea nitrogen, and serum creatinine; and serum C3, C4, antinuclear antibodies (ANA), anti-Sm, antiribonucleoprotein, antidouble-stranded DNA, and anti-nucleosome antibodies
We found that proteinuria (g/24 hour), blood urea nitrogen, and serum creatinine levels were all significantly greater in the LN-Bcell group than in the LN-non-B-cell group
Summary
Dysfunction of the B lymphocyte is considered to be involved in the pathogenesis of lupus nephritis (LN). B-cell activating factor (BAFF) regulates B lymphocyte proliferation and survival, and contributes to human autoimmune disease. Their role in renal inflammation is not well defined. As BAFF expression was strongly associated with B-cell infiltration, we hypothesize that altered B-cell differentiation and tolerance induced by excess BAFF may be central to the pathogenesis of LN. Little is known about the role of B cells as part of the infiltrating cell population This might be because B cells have classically been considered to exert long-range effects, mostly via activation in secondary lymphoid organs such as lymph nodes and the spleen, with subsequent proliferation and differentiation into antibody-producing plasma cells
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