| Rheumatoid Arthritis (RA) |
| RA is known to be associated with a group of DRB1 alleles that encode a similar sequence in the third hypervariable region of the DRb1 chain. The shared epitope sequence consists of the amino acid sequences QKRAA, QRRAA, or RRRAA from positions 70-74 of DRb1 and is encoded by some alleles of DRB1*04, *01, *14 and *10. Support for the shared epitope model was realized in significant part by international efforts from many different racial/ethnic groups. Although there are limitations to the shared epitope model, it has offered an appealing and unifying explanation for HLA-associations with RA. It is evident that genes other than those encoding HLA molecules are also contributory. HLA genes are estimated to account for only about one-third of the genetic risk of RA. In addition to genes on other chromosomes, non-HLA genes within the greater HLA complex are other potential candidates. The primary aim of the RA component is shared with that of the overall disease component of the IHWG i.e. to mount an international effort to identify candidate genes in the HLA complex that contribute to susceptibility or protection from disease, other than those that encode the HLA shared epitope sequence. The method of approach is described in the preceding summary by Erik Thorsby, Chair of the overall Disease Component. Briefly, a participant may be involved by recruiting study subjects in either of two different ways. The first method is case-control studies. This will require obtaining blood samples and some clinical information from RA patients and healthy controls from the same population. The second method is families studies. This will require obtaining blood samples from RA patients and from the patient's parents. We are fortunate in that we obtained a grant from the National Institutes of Health that provides financial support for the international cooperative effort. The grant gives us the ability to cover the cost of microsatellite testing for all participants. Therefore participants will be able to send DNA to one of our central collection sites along with HLA and clinical data. The DNA samples will be sent to a contracted laboratory outside of Paris, France where the microsatellite typing will be conducted without charge to the participant. Participants are also welcome to do their own microsatellite testing if they prefer. For those who do their own microsatellite typing they will be asked to also type a panel of reference DNA that will be sent to them from the IHWG for the purposes of standardization. The ultimate goal is to create a large and diverse database (without subject identifying information) that is publicly accessible. The RA collaborative group currently consists of 41 laboratories representing 28 countries. Each center will be responsible for recruiting patients, family members or HLA-matched controls, and will collect clinical and demographic information. Entry requirements for RA patients include: 1) Patients must meet American College of Rheumatology criteria 2) Patients must have onset age > 16 years of age. 3) Some demographic information and clinical information will be required e.g. age of onset, sex, family history including whether the patient has a twin. Desirable but not essential criteria include: i) radiographic studies of hands and wrists indicating erosions and/or joint space narrowing ii) no history of blood transfusion. Patients with younger age of onset and with both parents living are also desirable. The extensive database generated will also be used to address some other questions that are specific to RA. These include: 1) to evaluate microsatellite polymorphisms, single nucleotide polymorphisms and HLA genes according to RA outcome i.e. mild versus severe disease 2) to investigate alleles of DMA in RA susceptibility and severity 3) to assess the role of DQ and of position 86 of DRb1 in RA susceptibility and severity 4) to investigate the mother-child HLA relationship to ask whether exposure to non-host HLA molecules either from the mother or, in the case of women, from children modulates disease risk. Interested participants may contact the Rheumatoid Arthritis, J. Lee Nelson, MD, or Jean-Francois Eliaou, MD, the Chair and Co-Chair for the Rheumatoid Arthritis Section.
Rheumatoid Arthritis Questionnaire Back to Disease Component overview |