Susceptibility to demyelinating polyneuropathy in plasma cell dyscrasia may be influenced by amino acid position 9 of the HLA-DR beta chain

J Neuroimmunol. 1993 Mar;43(1-2):139-44. doi: 10.1016/0165-5728(93)90084-c.

Abstract

Fifty-five patients with plasma cell dyscrasias were investigated by genomic typing for HLA-DR and -DQ genes by restriction fragment length polymorphism, neurophysiology and for presence of anti-myelin-associated glycoprotein (MAG) antibodies. In 26 patients, a polyneuropathy (PN) of demyelinating type was established. Among these individuals, an association was found with the presence of a tryptophan amino acid residue at position 9 of the DR beta chain (P < 0.01). This position is part of the first hypervariable region of the DR beta chain, and may be of importance in determining preferential peptide-binding capacity of the HLA-DR molecule. The presence of anti-MAG antibodies in 15 out of 17 patients with an IgM M-component and demyelinating PN (14 of these 15 individuals carrying a tryptophan at position 9) supports the pathogenic role of an autoimmune response against MAG. The finding of an HLA class II association may indicate a pathogenic role of T cell immunity in this condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Demyelinating Diseases / etiology*
  • Demyelinating Diseases / genetics
  • Female
  • HLA-DQ Antigens / genetics
  • HLA-DR Antigens / genetics*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Myelin Proteins / immunology
  • Myelin-Associated Glycoprotein
  • Paraproteinemias / complications
  • Paraproteinemias / genetics
  • Paraproteinemias / immunology*
  • Polymorphism, Restriction Fragment Length
  • Structure-Activity Relationship

Substances

  • HLA-DQ Antigens
  • HLA-DR Antigens
  • Myelin Proteins
  • Myelin-Associated Glycoprotein