Strong association of dermatomyositis‐specific Mi‐2 autoantibodies with a tryptophan at position 9 of the HLA‐DRβ chain

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<jats:title>Abstract</jats:title><jats:p><jats:italic>Objective.</jats:italic> To characterize the clinical and immunogenetic features of patients with Mi‐2 autoantibodies.</jats:p><jats:p><jats:italic>Methods.</jats:italic> Eighteen adult white patients with Mi‐2 antibodies were clinically characterized and compared with 41 Mi‐2–negative dermatomyositis (DM) patients. HLA class I and class II typing for DRB alleles was done by microcytotoxicity assay and for DQA and DQB alleles by polymerase chain reaction–based oligotyping.</jats:p><jats:p><jats:italic>Results.</jats:italic> Seventeen of the 18 Mi‐2–positive patients had DM. Symptoms of scleroderma, lung involvement, and arthritis were less common in this group than in the Mi‐2–negative DM patients; the V‐sign rash and nailfold involvement were found more frequently. Mi‐2 antibodies were strongly associated with HLA‐DR7 (88% versus 24% in healthy controls), HLA–DQA1*0201 (86% versus 23%), and DR7 “homozygosity” (31% versus 0%). A tryptophan residue at position 9 of the HLA–DRβ chain was present in all Mi‐2–positive patients (100% versus 62%; homozygous in 81% versus 15%).</jats:p><jats:p><jats:italic>Conclusion.</jats:italic> Our results reemphasize the specificity of Mi‐2 antibodies for DM, and extend previous reports that Mi‐2 antibody production is associated with certain HLA class II antigens. We propose β9‐Trp as a candidate epitope on the HLA–DRβ chain as a prerequisite for this type of autoimmune response.</jats:p>

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