Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: Alfa-enolase and borderline antigens

Division of Nephrology and Laboratory on Pathophysiology of Uremia, G. Gaslini Children Hospital, Genoa, Italy.
Journal of proteomics (Impact Factor: 3.93). 05/2011; 74(10):2008-17. DOI: 10.1016/j.jprot.2011.05.021
Source: PubMed

ABSTRACT The identification of glomerular auto-antigens in idiopathic human membranous glomerulonephritis (MGN) is a crucial step towards the definition of the mechanisms of the disease. Recent 'in vivo' studies demonstrated a heterogeneous composition of glomerular immune-deposits in MGN biopsies only a part of which have been characterized. We studied with a proteomical approach IgGs eluted from laser capture microdissected glomeruli of 8 MGN patients and showed the existence of other three immune proteins in MGN glomeruli (α-enolase, elongation factor 2 and Glycyl Aminoacyl-tRNA Synthetase). One of these, i.e. α-enolase, fulfilled all criteria for being considered an auto-antigen. Specific IgG₁ and IgG₄ reacting with podocyte α-enolase were, in fact, eluted from microdissected glomeruli and Confocal- and Immuno Electron-Microscopy showed co-localization of α-enolase with IgG₄ and C5b-9 in immune-deposits. Serum levels of anti a-enolase IgG4 were determined in 131 MGN patients and were found elevated in 25% of cases. Overall, our data demonstrate that glomerular α-enolase is a target antigen of autoimmunity in human MGN. Circulating anti α-enolase auto-antibodies can be detected in sera of a significant quota of MGN patients. Like other auto-antigens, α-enolase may be implicated in the pathogenesis of human MGN.

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    • "Furthermore, high titer circulating IgG4 against these antigens was found in over 50% of patients as well. Bruschi et al. [28] found circulating IgG4 antibodies against α-enolase in the serum of 25% of 131 iMN patients. Confocal-and immuno electron-microscopy showed co-localization of α-enolase with IgG4 and C5b-9 in immune deposits. "
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