Surface binding autoantibodies and their functional effects in dermatomyositis and polymyositis

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SinghPratibha_2010_09_21.pdf (7.2 MB)

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2010

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DOI:
http://dx.doi.org/10.22029/jlupub-13604

Abstract

Polymyositis and Dermatomyositis are both inflammatory muscle diseases. Althoughdifferent autoantibodies have been reported in DM/PM, pure muscle specific antigensare rarely known.The current study focuses on identification of proteins, responding to antibodies frominflammatory myositis and screens those proteins using proteomic approach. At thesame time the functional effects of the specific autoantibodies has also beeninvestigated by using cytotoxicity assay and calcium imaging.Flow cytometric antibody binding showed that myositis patients have autoantibodiesagainst surface epitopes of muscle cells but not to endothelial cells. As statins havebeen implicated in inducing myopathy with increased expression of MHC class I inmuscle cells, statin treated cells have been analysed for surface binding of patient sera.Patients sera showed increased binding to mevastatin and simvastatin treated primarymuscle cells but not to rhabdomyosarcoma cells. The 2D approach has been used toidentify muscle specific autonantigens but we could not find any specific autoantigens.Interestingly the purified IgG from myositis patients showed cytotoxic effects againstendothelial cells but not to muscle cells. In further assessing the functional effects ofautoantibodies It has been found that the purified patients IgG but not control IgGchanged Ca2+ influx in endothelial cells. When analysed for statins induced changes inMHC class I expression and other proteins (TAP and LMP) at protein and RNA level,statins alone surprisingly reduced the expression of MHC I in SKMC and had no effecton MHC I in TE671. Statins potentiated the MHC I-inducing effect of IFN-gamma inTE671, but not in SKMC, neither on the protein level, nor on mRNA level. This leads tothe conclusion that the increased muscle MHC I expression in statin-induced myopathymight not be induced directly by statins themselves. The increased binding of myositissera to stain treated muscle cells and to primary muscle cells and the functional effectsof these autoantibodies point to a pathogenic role of the humoral immune system ininflammatory muscle diseases.

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