title: Susceptibility to demyelinating polyneuropathy in plasma cell dyscrasia may be influenced by amino acid position 9 of the HLA-DR beta chain.
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.
authors.affiliation: Department of Neurology, University Hospital, Linköping, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Vrethem
authors.forename: J
authors.initials: J
authors.lastname: Ernerudh
authors.forename: M
authors.initials: M
authors.lastname: Cruz
authors.forename: O
authors.initials: O
authors.lastname: Olerup
authors.forename: G
authors.initials: G
authors.lastname: Solders
authors.forename: B
authors.initials: B
authors.lastname: Ekstedt
authors.forename: O
authors.initials: O
authors.lastname: Andersen
authors.forename: J
authors.initials: J
authors.lastname: Hillert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003711:Demyelinating Diseases / Q000209:etiology* / Q000235:genetics; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009185:Myelin Proteins / Q000276:immunology; D018992:Myelin-Associated Glycoprotein; D010265:Paraproteinemias / Q000150:complications / Q000235:genetics / Q000276:immunology*; D012150:Polymorphism, Restriction Fragment Length; D013329:Structure-Activity Relationship
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein