Is HLA class II susceptibility to primary antiphospholipid syndrome different from susceptibility to secondary antiphospholipid syndrome?

Abstract

To assess whether the major histocompatibility complex (MHC) profile of patients presenting with primary antiphospholipid syndrome (PAPS) is different from that of patients with secondary antiphospholipid syndrome (SAPS), we studied 123 patients, 34 of whom presented PAPS and 35 SAPS due to systemic lupus erythematosus (SLE), 54 SLE patients without antiphospholipid syndrome (APS), and 166 controls. HLA-DRB1 and DQB1 alleles were typed using amplified DNA hybridized with sequence-specific primers. Compared to controls, PAPS patients exhibited a nonsignificantly increased frequency of DR53-associated alleles, and SAPS patients presented an increased frequency of HLA-DRB1*03 alleles (corrected P = 0.05). In addition, HLA-DRB1*03 alleles were over-represented in SAPS patients presenting anticardiolipin antibody (aCL) (Pc = 0.02), in SLE patients as a whole (Pc < 0.0001), and in SLE patients without APS (Pc = 0.02). The frequency of aCL among SLE patients presenting or not HLA-DRB1*03 alleles was closely similar. A trend to an increase in the frequency of the DQB1*0604 allele (14.3 versus 4.2%, P = 0.03) and of the DQB1*0302 allele (31.4 versus 12.7%, P = 0.01) was observed in SAPS. Taken together, these results indicate that the association of SAPS with HLA-DRB1*03 is due to the association with SLE and is not due to aCL, and suggest that the HLA class II profile of PAPS is different from that of SAPS.

Val/Leu247 Polymorphism of β2‐glycoprotein I in Brazilian Patients with Antiphospholipid Syndrome—A Genetic Risk Factor?

“…19,21,22 Additional studies will be necessary to determine how the Val/Leu 247 polymorphism in the β2-GPI gene could influence the development of APS and the production of anti-β2-GPI antibodies. The involvement of other β2-GPI polymorphisms, HLA class II genes, 23 and environmental variables also needs to be considered. 24,25…”

Val/Leu247 polymorphism of β2‐glycoprotein I and thrombosis in Chinese patients with SLE

“…Additional studies will be necessary to distinguish how and which domain of β 2 GPI the anti‐β 2 GPI antibodies are directed against, how β 2 GPI polymorphism influences the production of anti‐β 2 GPI antibodies and what other β 2 GPI polymorphisms, human leukocyte antigen class genes and environmental variables should also be taken into account when considering anti‐β 2 GPI antibody production.…”

“…The cumulative results showed that each domain of b 2 GPI has been indicated as the location where anti-b 2 GPI antibodies may bind, and not all anti-b 2 GPI IgG antibodies have the same epitope specificity. Additional studies will be necessary to distinguish how and which domain of b 2 GPI the anti-b 2 GPI antibodies are directed against, how b 2 GPI polymorphism influences the production of anti-b 2 GPI antibodies and what other b 2 GPI polymorphisms, human leukocyte antigen class genes [17] and environmental variables should also be taken into account when considering anti-b 2 GPI antibody production.…”

Primary versus secondary antiphospholipid syndrome: Is this lupus or not?

“…These studied have not compared PAPS and SAPS. In Brazil, a genetically diverse population, Freitas et al [21] studies 34 patients with PAPS, 35 patients with SAPS with SLE, 54 SLE patients without APS, and 166 controls. They found that HLA-DRB1*03 alleles were increased in SAPS and in SLE patients as a whole but not in PAPS or controls.…”