Low copy numbers of complement and deficiency are risk factors for myositis, its subgroups and autoantibodies.

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.