Strong association of dermatomyositis-specific Mi-2 autoantibodies with a tryptophan at position 9 of the HLA-DR beta chain.
OBJECTIVE
To characterize the clinical and immunogenetic features of patients with Mi-2 autoantibodies.


METHODS
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.


RESULTS
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-DR beta chain was present in all Mi-2-positive patients (100% versus 62%; homozygous in 81% versus 15%).


CONCLUSIONS
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 beta 9-Trp as a candidate epitope on the HLA-DR beta chain as a prerequisite for this type of autoimmune response.
Mierau
R
R
Research Institute of Rheumatic Diseases, Aachen, Germany.
Dick
T
T
Bartz-Bazzanella
P
P
Keller
E
E
Albert
E D
ED
Genth
E
E
D000251:Adenosine Triphosphatases; D000328:Adult; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001483:Base Sequence; D004265:DNA Helicases; D003882:Dermatomyositis / Q000276:immunology* / Q000503:physiopathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D008875:Middle Aged; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D014364:Tryptophan / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; C115323:CHD4 protein, human; D000939:Epitopes; D006684:HLA-DR Antigens; D015345:Oligonucleotide Probes; D014364:Tryptophan; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000251:Adenosine Triphosphatases; D004265:DNA Helicases