Strong association of dermatomyositis-specific Mi-2 autoantibodies with a tryptophan at position 9 of the HLA-DR beta chain

Arthritis Rheum. 1996 May;39(5):868-76. doi: 10.1002/art.1780390521.

Abstract

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%).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases*
  • Adult
  • Amino Acid Sequence
  • Antibody Specificity
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • Base Sequence
  • DNA Helicases*
  • Dermatomyositis / immunology*
  • Dermatomyositis / physiopathology
  • Epitopes / immunology
  • Female
  • HLA-DR Antigens / chemistry*
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology
  • Humans
  • Male
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Middle Aged
  • Molecular Sequence Data
  • Oligonucleotide Probes / genetics
  • Tryptophan / chemistry*
  • Tryptophan / genetics
  • Tryptophan / immunology*

Substances

  • Autoantibodies
  • Autoantigens
  • CHD4 protein, human
  • Epitopes
  • HLA-DR Antigens
  • Oligonucleotide Probes
  • Tryptophan
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Adenosine Triphosphatases
  • DNA Helicases