HLA-DPB1 alleles association of anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus

Abstract

Our objective was to determine the HLA-DPB1 allele associations of anticardiolipin (aCL) and anti-beta₂ GPI (aβ₂ GPI) antibodies, and of clinical manifestations of the antiphospholipid syndrome (APS), in systemic lupus erythematosus(SLE). We studied 577 European patients with SLE. aCL and aβ₂ GPI antibodies were measured by ELISA. Molecular typing of HLA-DPB1 locus was performed by polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. aCL showed positive association with -DPB1*1501 (P 0.005, OR 7.4), and -DPB1*2301 (P 0.009, OR 3.3). aβ₂ GPI showed positive association with -DPB1*0301 (P 0.01, OR 1.9), and -DPB1*1901 (P 0.004, OR 8.1). In addition, livedo reticularis was associated with -DPB1*1401, and Raynaud’s phenomenon with -DPB1*2001. In conclusion, HLA-DPB1 locus may contribute to the genetic predisposition to develop antiphospholipid antibodies and clinical manifestations of the APS in patients with SLE.

Keywords

anti-β2 GPI antibodies anticardiolipin antibodies antiphospholipid syndrome HLA HLA-DPB1 locus systemic lupus erythematosus

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References

Ahearn JM , Provost TT , Dorsch CA et al. Interrelationships of HLA-DR, MB and MT phenotypes, autoantibody expression, and clinical features in systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1031-1040 .

Smolen JS , Klippel JH , Penner E et al. HLA-DR antigens in systemic lupus erythematosus: association with specificity of autoantibody responses to nuclear antigens . Ann Rheum Dis 1987; 46: 457-462 .

Lulli P , Sebastiani GD , Trabace S et al. HLA antigens in Italian patients with systemic lupus erythematosus: evidence for the association of DQw2 with the autoantibody response to extractable nuclear antigens . Clin Exp Rheumatol 1991; 9: 475-479 .

Viard J , Amoura Z , Bach J. Association of anti-beta2-glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus . Am J Med 1992: 93: 181-186 .

Cabiedes J , Cabral AR , Alarcon-Segovia D. Clinical manifestations of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more strongly with anti-beta2-glycoprotein-I than with antiphospholipid antibodies . J Rheumatol 1995; 22: 1899-1906 .

Fleck RA , Rapaport SI , Rao LVM. Antiprothrombin antibodies and the lupus anticoagulant . Blood 1988; 72: 512-519 .

Matsuda J , Saitoh N , Gohchi K , Gotoh M , Tsukamoto M. Anti-annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody . Am J Hematol 1994; 47: 56-58 .

Berard M , Chantome R , Marcelli A , Boffa M. Antiphosphatidylethanolamine antibodies as the only antiphospholipid antibodies. I. Association with thrombosis and vascular cutaneous diseases . J Rheumatol 1996; 23: 1369-1374 .

Horkko S , Miller E , Dudi E et al. Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids . J Clin Invest 1996; 98: 815-825 .

10.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of SLE . Arthritis Rheum 1982; 25: 1271-1277 .

11.

Sebastiani GD , Galeazzi M , Tincani A et al. Anticardiolipin and anti-b2GPI antibodies in a large series of European patients with systemic lupus erythematosus: prevalence and clinical associations . Scand J Rheumatol 1999; 28: 344-351 .

12.

Galeazzi M , Sebastiani GD , Tincani A et al. HLA class II associations of anticardiolipin and anti-b2GPI antibodies in a large series of European patients with systemic lupus erythematosus . Lupus 2000; 9: 47-55 .

13.

Kimura A , Sasazuki T. Eleventh International Histocompatibility Workshop reference protocol for the HLA-DNA typing technique. In: Tsuji K , Aizawa M , Sasazuki T (eds). HLA 1991. Oxford: Oxford University Press , 1992, pp 397-419.

14.

Genetic diversity of HLA functional and medical implications . Proceedings of XII Histocompatibility Workshop and Conference. In: Charron D (ed). HLA EDK 1997, Vol I, p 496-496 .

15.

Davies EJ , Hutchings CJ , Hillarby MC et al. HLA-DP does not contribute towards susceptibility to systemic lupus erythematosus . Ann Rheum Dis 1994; 53: 188-190 .

16.

Yao Z , Hartung K , Deicher HG et al. DNA typing for HLA-DPB1-alleles in German patients with systemic lupus erythematosus using the polymerase chain reaction and DIG-ddUTP-labelled oligonucleotide probes. Members of SLE Study Group . Eur J Immunogenet 1993; 20: 259-266 .

17.

Bishof NA , Welch TR , Beischel LS , Carson D , Donnelly PA. DP polymorphism in HLA-A1, -B8, -DR3 extended haplotypes associated with membranoproliferative glomerulonephritis and systemic lupus erythematosus . Pediatr Nephrol 1993; 7: 243-246 .

18.

Yao Z , Hartung K , Ehrfeld H et al. No direct correlation between HLA DPB1 and antibodies against recombinant Ro (SS-A)/La (SS-B) proteins in systemic lupus erythematosus. SLE Study Group . Rheumatol Int 1993; 13: 155-158 .

19.

Reveille JD , Brady J , MacLeod-St Clair M , Durban E. HLA-DPB1 alleles and autoantibody subsets in systemic lupus erythematosus, Sjogren’s syndrome and progressive systemic sclerosis: a question of disease relevance . Tissue Antigens 1992; 40: 45-48 .

20.

Reveille JD , Anderson KL , Schrohenloher RE , Acton RT , Barger BO. Restriction fragment length polymorphism analysis of HLA-DR, DQ, DP and C4 alleles in Caucasians with systemic lupus erythematosus . J Rheumatol 1991; 18: 14-18 .

21.

Galeazzi M , Sebastiani GD , Passiu G et al. HLA-DP genotyping in patients with systemic lupus erythematosus: correlations with autoanti-body subsets . J Rheumatol 1992; 19: 42-46 .

22.

Sebastiani GD , Galeazzi M , Passiu G et al. Genetics of antiendothelial cell antibodies in systemic lupus erythematosus: the role of HLA-DP alleles . Contrib Nephrol 1992; 99: 102-107 .