Southern blot analysis of HLA-DP gene polymorphisms in Caucasoid rheumatoid arthritis (RA) patients and controls

Abstract

Despite extensive analysis of the incidence of HLA-DR and HLA-DQ allele frequencies in defined autoimmune disease groups, there is very little information available on HLA-DP allele frequencies. This is largely because HLA-DP typing has until recently been restricted to primed lymphocyte typing (PLT). However, allelic polymorphism of the HLA-DP subregion can now be studied by Southern blot analysis or genotyping with DPA1 and DPB1 probes. By direct counting of allele-specific DNA fragments, we have analyzed the frequencies of five major DP genotypes (DPw1, DPw2, DPw3/6, DPw4, and DPw5), in a large number of Caucasoid rheumatoid arthritis (RA) patients (n = 74), and controls (n = 91). The predicted frequency of DP alleles in both patient and control groups was comparable to PLT-determined DP allele frequencies in normal Caucasoids. However, the gene frequency of DPw4 was increased in the RA patients, with 51% of the patients studied scoring as DPw4, 4 homozygotes. With the exception of one possible combination (DPw5 and DRw6) in the controls, no significant linkage disequilibrium was detected between DP and DR alleles in either patient or control groups. Thus the prevalence of DPw4 in the RA patients is independent of any disease association with the DR loci, and may represent a new class II association with RA.

HLA-DP Allele-Specific T Cell Responses to Beryllium Account for DP-Associated Susceptibility to Chronic Beryllium Disease

“…More recently, the same group has demonstrated that the CD-associated heterodimer is used as a restriction element in the recognition of gliadin peptides by T cells derived from the gut of CD patients (22). HLA-DP associations have also been described in autoimmune diseases, such as CD (23), insulin-dependent diabetes mellitus (24), pauciarticular juvenile rheumatoid arthritis (25)(26)(27), and juvenile ankylosing spondylitis (28). In addition, an HLA-DP association has recently been demonstrated in primary biliary cirrhosis (29), in childhood common acute lymphoblastic leukemia (30), and also in Thai individuals with enhanced vaccine-induced Ab response to a malaria sporozoite Ag (31).…”

Hla‐dr/Dq/Dp Interactions in Rheumatoid Arthritis

“…Association of HLA-DPB1*0401 to RA has been reported from studies of Caucasian RA patients (Stephens et al, 1989;Gao et al, 1991;Perdriger et al, 1992;Perdriger et al, 1996). Interestingly, the HLA-DPB chain has an sequence analogue (position 67-71, EEKRA) to the (Q)R/KRAA sequence of the HLA-DRB chain.…”

“…These studies could demonstrate an association of HLA-DPB1*0401 with susceptibility to RA (Stephens et al, 1989;Gao et al, 1991;Perdriger et al, 1992;Perdriger et al, 1996). These studies could demonstrate an association of HLA-DPB1*0401 with susceptibility to RA (Stephens et al, 1989;Gao et al, 1991;Perdriger et al, 1992;Perdriger et al, 1996).…”

“…Since HLA-DR and -DQ alleles are in strong linkage disequilibrium, most studies have focused on HLA-DPB1 alleles. These studies could demonstrate an association of HLA-DPB1*0401 with susceptibility to RA (Stephens et al, 1989;Gao et al, 1991;Perdriger et al, 1992;Perdriger et al, 1996). The HLA-DPB1*0301 allele has been associated with seronegative RA (Gao et al, 1991) and the HLA-DPB1*0201 allele with non-erosive disease or seronegative disease (Singal et al, 1994;Carthy et al, 1995).…”

HLA-DP typing by amplified fragment length polymorphisms (AFLPs)

“…HLA-DP specificities have also been shown to be associated with several autoimmune diseases (Stephens et al 1989;Bugawan et al 1989).…”