HLA class II alleles associations of anticardiolipin and anti b2GPI antibodies in a large series of European patients with systemic lupus erythematosus

Abstract

The objective of this study was to determine the HLA class II associations of the anticardiolipin (aCL) and anti-beta2GPI (abeta2GPI) antibodies in a large series of European patients with systemic lupus erythematosus (SLE). A cohort of 577 European SLE patients was enrolled. aCL and abeta2GPI were measured by ELISA methods. Molecular typing of HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1 loci was performed by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. aCL of IgG, IgM and IgA isotypes were detected in 22.8%, 14% and 13.9% of patients, respectively. IgG and IgM abeta2GPI were detected in 20% of patients. aCL showed positive association with HLA DRB1*04, DRB1*0402, DRB1*0403, DRB1*07, DRB3*0301, DQA1*0201, DQA1*0301, DQB1*0302, and negative association with DQA1*0501, DRB3*0202. abeta2GPI showed positive association with DRB1*0402, DRB1*0403, DQB1*0302. DRB1*0402 carried the highest relative risk for the presence of both aCL (RR=8. 1) and abeta2GPI (RR=4.6). Our results confirm the already described associations of aCL with HLA DR4 and DR7, but also demonstrate that, among the alleles at the DRB1*04 locus, the *0402 was most represented both in aCL and in abeta2GPI positive patients. In addition, HLA class II associations of abeta2GPI are for the first time extensively examined in a large cohort of European SLE patients.

β2-Glycoprotein I-specific T Cells Are Associated with Epitope Spread to Lupus-related Autoantibodies

“…Notably, the human T cell clones responded to peptide 23 presented in the context of a single HLA-DR allele, DRB1*0403. Identification of HLA-DRB1*0403 as the allele capable of presenting peptide 23 to ␤ 2 GPI-reactive T cells is interesting, as this MHC allele has been shown to be strongly associated with the presence of anti-phospholipid antibodies (both anti-CL and anti-␤ 2 GPI) in a European cohort of SLE patients (24). Together with our findings in mice, these data suggest that the T cell response to ␤ 2 GPI is restricted by MHC class II haplotype in both humans and mice.…”

Genetics of Antiphospholipid Syndrome

“…Alternatively, these alleles may be apparent only because of their linkage disequilibrium with an as yet unidentified primarily involved HLA locus, or they could act in cooperation with other genes, possibly even outside the MHC. For instance, some reports indicate that aCL are associated with C4A or C4B null alleles (Galeazzi et al, 2000). In addition, the different aPL (anticardiolipin antibodies, lupus anticoagulant, anti-β 2 GPI antibodies, antiphosphatidylserine/prothrombin antibodies) show similar HLA association, again independent of the clinical context (primary APS or SLE), and across various ethnic groups.…”

Autoimmune Studies and HLA Associations in SLE Patients from Mumbai

“…Recently a significant association and increased evidence of direct involvement in the pathogenesis of tissue injury by the anti SS-A/ Ro and SS-B/ La antibodies are reported (Mavragani et al 2000). In SLE multiple loci within the MHC have been implicated in susceptibility like HLA class II alleles, Complement components and TNF loci (Naves et al 1998;Gladman et al 1999;Galeazzi et al 2000;Huang et al 2001;Azizah et al 2001;Shankarkumar et al 2003). HLA DQ1 and DQ2 are also found to be associated with Ro, La, Sm and dsDNA autoantibodies.…”