Identification of skeletal muscle autoantigens by expression library screening using sera from autoimmune rippling muscle disease (ARMD) patients.
Novel forms of contractile regulation observed in skeletal muscle are evident in neuromuscular diseases like rippling muscle disease (RMD). Previous studies of an autoimmune form of RMD (ARMD) identified a very high molecular weight skeletal muscle protein antigen recognized by ARMD patient antisera. This study utilized ARMD and myasthenia gravis (MG) patient antisera, to screen a human skeletal muscle cDNA library that subsequently identified proteins that could play a role in ARMD. Based on nucleotide sequence analysis, three distinct ARMD antigens were identified: titin Isoform N2A, ATP synthase 6, and PPP1R3 (protein phosphatase 1 regulatory subunit 3). The region of titin identified by ARMD antisera is distinct from the main immunogenic region (MIR) recognized by classical MG antibodies. Sera from classical MG patient identifies an expressed sequence corresponding to the titin MIR. Although the mechanism of antibody penetration is not known, previous studies have shown that rippling muscle antibodies affect the contractile machinery of myofibers resulting in mechanical sensitivity. Titin's role as a modulator of muscle contractility makes it a potential target in understanding muscle mechanosensitive regulation.
Watkins
Thomas C
TC
Biomedical Sciences Program, Kent State University, Kent, Ohio 44555-3602, USA.
Zelinka
Lisa M
LM
Kesic
Matt
M
Ansevin
Carl F
CF
Walker
Gary R
GR
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000032:analysis*; D001327:Autoimmune Diseases / Q000276:immunology*; D064211:Connectin; D006801:Humans; D007106:Immune Sera; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000276:immunology; D018482:Muscle, Skeletal / Q000276:immunology*; D009135:Muscular Diseases / Q000276:immunology*; D009157:Myasthenia Gravis / Q000276:immunology; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000276:immunology; D011494:Protein Kinases / Q000235:genetics / Q000276:immunology; D054645:Protein Phosphatase 1; D020539:Sequence Analysis, Protein
D001324:Autoantigens; D064211:Connectin; D007106:Immune Sera; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases; C114205:PPP1R3A protein, human; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C412204:ATP synthase subunit 6; D025261:Mitochondrial Proton-Translocating ATPases