Low copy numbers of complement and deficiency are risk factors for myositis, its subgroups and autoantibodies
Annals of the rheumatic diseases
autoantibodies; dermatomyositis; polymyositis
BACKGROUND: Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complement in IIM pathology was unknown. METHODS: We elucidated the gene copy number (GCN) variations of total , and and in 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion. RESULTS: The large study populations helped establish the distribution patterns of various GCN groups. Low GCNs of (=2+3) and deficiency (=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28-2.91), p=5.0×10 for , and 2.82 (2.48-3.21), p=7.0×10 for deficiency. Contingency and regression analyses showed that among patients with deficiency, the presence of became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% had with an OR of 11.02 (1.44-84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies. CONCLUSIONS: deficiency is relevant in dermatomyositis, is important in IBM and both deficiency and contribute interactively to risk of polymyositis.
Zhou, Danlei; King, Emily H.; Rothwell, Simon; Krystufkova, Olga; Notarnicola, Antonella; Coss, Samantha; Abdul-Aziz, Rabheh; Miller, Katherine E.; Dang, Amanda; Yu, G Richard; Drew, Joanne; Lundström, Emeli; Pachman, Lauren M.; Mamyrova, Gulnara; Curiel, Rodolfo V.; De Paepe, Boel; De Bleecker, Jan L.; Payton, Antony; Ollier, William; O'Hanlon, Terrance P.; Targoff, Ira N.; Flegel, Willy A.; Sivaraman, Vidya; Oberle, Edward; Akoghlanian, Shoghik; Driest, Kyla; Spencer, Charles H.; Wu, Yee Ling; Nagaraja, Haikady N.; Ardoin, Stacy P.; Chinoy, Hector; and Rider, Lisa G., "Low copy numbers of complement and deficiency are risk factors for myositis, its subgroups and autoantibodies" (2022). GW Authored Works. Paper 1585.