Vimentin Is a Dominant Target of In Situ Humoral Immunity in Human Lupus Tubulointerstitial Nephritis
Kinloch AJ, Chang A, Ko K, et al
Arthritis Rheumatol. 2014;66:3359-3370
In this experiment, Kinloch and colleagues laser-captured B cells from biopsy specimens from patients with systemic lupus erythematosus (SLE) and tubulointerstitial nephritis (TIN), produced monoclonal antibodies, and characterized antigens in order to identify the dominant driving autoantigen(s) in TIN.
Noncitrullinated vimentin was identified as the only reactive autoantigen, with most monoclonal antibodies binding directly to it. Vimentin was also highly expressed on inflammatory cells within the tubulointerstitium. Furthermore, circulating levels of autoantibodies to vimentin—and not anti–double-stranded DNA antibodies—were strongly correlated with severe TIN.
In patients with SLE, the degree of TIN is a powerful predictor of progressive renal disease and renal failure. Thus, identifying the underlying causes of TIN is a critical step in improving treatment outcomes for these patients.
The finding that vimentin is a major antigenic target in TIN is an important step towards identifying potential pharmacologic targets to treat TIN. Furthermore, the finding that autoantibodies to vimentin are associated with severe TIN could provide a new biomarker to predict the severity and prognosis of TIN in patients with SLE.
The authors mention that in SLE, mature naive B cells have some reactivity to cytoplasmic antigens and that these cells may serve as precursors to cells expressing anti-vimentin antibodies. Because there are some data suggesting that antibodies to neutrophil cytoplasmic antibodies (ANCA) may also be associated with more severe lupus nephritis, future research should evaluate how each of these autoantibody systems contributes to the pathogenesis of lupus nephritis.
As the accompanying editorial states, Kinloch and colleagues should be congratulated for using careful experimental techniques and only small amounts of human tissue to provide such important data contributing to the understanding of the pathogenesis of TIN. We should look forward to future research that can use these techniques and others to elucidate mechanisms of autoimmune disease development.
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Cite this: Kevin D. Deane. Predicting Renal Disease in Lupus Nephritis - Medscape - Jan 27, 2015.