Research on autoimmune processes involved in
glomerulonephritis has been for years based on experimental models. Recent progress in proteomics has radically modified perspectives:
laser microdissection and proteomics were crucial for an in vivo analysis of
autoantibodies eluted from human biopsies.
Lupus nephritis has been the subject of recent independent researches. Main topics have been the definition of renal autoimmune components in human lupus biopsies; methods were
laser capture of glomeruli and/or of single cells (CD38+ or Ki-67+) from tubulointerstitial areas as starting step followed by elution and characterization of renal
antibodies by proteomics. The innovative approach highlighted different panels of
autoantibodies deposited in glomeruli and in tubulo-interstitial areas that actually represented the unique autoimmune components in these patients.
IgG2 was the major isotype; new podocyte
proteins (αenolase,
annexin AI) and already known implanted molecules (
DNA,
histone 3, C1q) were their target
antigens in glomeruli.
Vimentin was the
antigen in tubulo-interstitial areas. Matching renal
autoantibodies with serum allowed the definition of a typical
autoantibody serum map that included the same anti-αenolase, anti-
annexin AI, anti-
DNA, and anti-
histone 3
IgG2 already detected in renal tissue. Serum levels of specific
autoantibodies were tenfold increased in patients with
lupus nephritis allowing a clear differentiation from both
rheumatoid arthritis and other
glomerulonephritis. In all cases, targeted
antigens were characterized as components of lupus NETosis. Matching renal/serum
autoantibody composition in vivo furnishes new insights on human
lupus nephritis and allows to refine composition of circulating
antibodies in patients with lupus. A thoughtful passage from bench to bedside of new knowledge would expand our clinical and therapeutic opportunities.