Clinical Study Association of Intrarenal B-Cell Inﬁltrates with Clinical Outcome in Lupus Nephritis: A Study of 192 Cases
Yan Shen,1 Chuan-Yin Sun,1 Feng-Xia Wu,1 Yi Chen,1 Min Dai,1 Yu-Cheng Yan,2 and Cheng-De Yang1
of Rheumatology, RenjiHospital, Shanghai Jiaotong University School of Medicine, 145 Shan Dong Zhong Road, Shanghai 200001, China 2 Department of Nephrology, Renji Hospital, Shanghai Jiaotong University School of Medicine, 145 Shan Dong Zhong Road, Shanghai 200001, China Correspondence should be addressed to Cheng-De Yang, email@example.com Received 4 February 2012; Revised 25 April 2012; Accepted 25 April 2012Academic Editor: Harris Perlman Copyright © 2012 Yan Shen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Lupus nephritis (LN) remains a major cause of morbidity and end-stage renal disease. Dysfunction of B lymphocytesis thought to be important in the pathogenesis of SLE/LN. Intrarenal B cells have been found in several forms of inﬂammatory kidney diseases although their role in LN renal is not well deﬁned. Methods. Intrarenal B cells were analyzed in 192 renal biopsies from patients diagnosed with lupus nephritis. Immunohistochemical staining of serial sections was performed for each LN patient using CD20,CD3, and CD21 antibodies. Results. Intrarenal B cells were more likely to be associated with class IV LN and were mainly distributed in the renal interstitium, with very few in the glomerulus. The systemic lupus erythematosus disease activity index (SLEDAI), blood urea nitrogen, and serum creatinine levels were all signiﬁcantly greater in the LN-B cell groups (all P < 0.05). LN renal activity andchronicity indices correlated with B-cells inﬁltrates (all P < 0.0001). Renal biopsies were classiﬁed into four distinct categories according to the organizational grade of inﬂammatory cell inﬁltrates. Germinal center- (GC-) like structures were not identiﬁed in any LN biopsies. Conclusion. It is hypothesized that intrarenal B cells enhance immunological responses and exaggerate the local immuneresponse to persisting autoimmune damage in the tubulointerstitium.
Lupus nephritis (LN) is the main cause of morbidity and mortality in systemic lupus erythematosus (SLE) . LN develops in up to 60% of SLE patients during the course of the disease and its treatment remains a challenge . LN is characterized by immune complex deposition and inﬂammation in glomeruli and thetubulointerstitium. Many studies have indicated that systemic loss of B-cell tolerance results in the local deposition of immune complexes [3, 4]. Intrarenal mononuclear cells have long been believed to be composed mainly of monocytes and T cells. Classically, B cells have been considered to exert long-range eﬀects mostly via activation in secondary lymphoid organs such as lymph nodes and spleen, withsubsequent proliferation and diﬀerentiation into antibody-producing plasma cells. Consequently, few researchers have focused on the role of
B cells as part of the renal inﬁltrate. However, a high prevalence of intrarenal B cells has been noted in immunemediated diseases, such as renal transplant rejection and glomerulonephritis [5–7] thus indicating that local B-cell inﬁltrates play a role intissue injury such as tissue ﬁbrosis, neolymphangiogenesis, and ectopic lymphogenesis . Investigations in the MRL/lpr mouse model of lupus nephritis have indicated that B cells exert a pathogenic role in the absence of soluble autoantibody production . Moreover, Steinmetz et al. observed that the majority of B cells in lupus nephritis patients displayed a mature non-antibodyproducing...