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Felty's syndrome (FS) is a rare complication of rheumatoid arthritis (RA) previously shown to be strongly associated with HLA-DR4 and less significantly with HLA-DQw7. To map more precisely the HLA locus responsible for susceptibility to FS, we have examined HLA-DR4 and DQ beta-chain polymorphisms in FS patients and controls using restriction fragment length polymorphism analysis and polymerase chain reaction amplification in conjunction with oligonucleotide probing. The increased frequency of DR4 in FS (93% vs. 32% controls) was due almost entirely to enrichment for the Dw4 subtype (88% vs. 20% controls) with a secondary increase of the Dw14 subtype. Dw10 and Dw13 subtypes of DR4 were absent from the patient group. Increase in DQw7 frequency among DR4 FS patients could be accounted for by linkage disequilibrium between Dw4 and DQw7 alleles. Whereas susceptibility to RA is strongly associated with a conserved HLA-DR beta epitope associated with several DRB1 alleles, it is primarily the Dw4 allele which is associated with progression to Felty's syndrome. The finding that amino acid sequence variation at the DR4B1 locus rather than DQB1 is associated with development of FS will have important implications for the development of novel immunotherapies which are major histocompatibility complex allele-dependent.

Original publication

DOI

10.1016/0198-8859(91)90117-r

Type

Journal article

Journal

Human immunology

Publication Date

09/1991

Volume

32

Pages

56 - 64

Addresses

Molecular Immunogenetics Unit, UMDS, Guy's Hospital, London, United Kingdom.

Keywords

Humans, Felty's Syndrome, Amino Acids, Oligonucleotide Probes, HLA-DQ Antigens, HLA-DR4 Antigen, Blotting, Southern, Chromosome Mapping, Polymerase Chain Reaction, Base Sequence, Haplotypes, Polymorphism, Genetic, Polymorphism, Restriction Fragment Length, Molecular Sequence Data