Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.


Journal article


Hum immunol

Publication Date





56 - 64


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