Plasma Tumor Necrosis Factor α Levels and the –238* A Promoter Polymorphism in Patients with Antiphospholipid Syndrome

M. L. Bertolaccini; T. Atsumi; J. S. Lanchbury; A. R. Caliz; K. Katsumata; R. W. Vaughan; E. Kondeatis; M. A. Khamashta; T. Koike; G. R. V. Hughes

doi:10.1055/s-0037-1615676

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2001; 85(02): 198-203
DOI: 10.1055/s-0037-1615676

Rapid Communications

Schattauer GmbH

Plasma Tumor Necrosis Factor α Levels and the –238* A Promoter Polymorphism in Patients with Antiphospholipid Syndrome

M. L. Bertolaccini

¹Lupus Research Unit, The Rayne Institute, St. Thomas’ Hospital, London, UK

²Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan

,

T. Atsumi

²Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan

,

J. S. Lanchbury

³Molecular Immunogenetics, Department of Rheumatology, GKT School of Medicine, King’s College

,

A. R. Caliz

¹Lupus Research Unit, The Rayne Institute, St. Thomas’ Hospital, London, UK

,

K. Katsumata

¹Lupus Research Unit, The Rayne Institute, St. Thomas’ Hospital, London, UK

,

R. W. Vaughan

⁴Tissue Typing Department, Guy’s Hospital, London, UK

,

E. Kondeatis

⁴Tissue Typing Department, Guy’s Hospital, London, UK

,

M. A. Khamashta

¹Lupus Research Unit, The Rayne Institute, St. Thomas’ Hospital, London, UK

,

T. Koike

²Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan

,

G. R. V. Hughes

¹Lupus Research Unit, The Rayne Institute, St. Thomas’ Hospital, London, UK

› Institutsangaben

Abstract

Summary

Objectives. To explore the possible involvement of the proinflammatory and prothrombotic cytokine TNFα in APS by determining the plasma levels in patients and to test for association of TNFA promoter polymorphisms and HLA class II genotypes with both plasma TNF and disease. Patients and Method. We studied 83 Caucasoid patients with APS and two groups of healthy controls. TNFα levels were determined in plasma from 35 patients’ and 21 controls using a highly sensitive sandwich ELISA. The full patient group was genotyped together with 95 ethnically matched healthy controls. -308 and -238 TNFA promoter polymorphisms were assessed by ARMS-PCR. HLA-DQB1, DQA1 and DRB1 genotypes were determined by PCR using sequence specific primers. Results. TNFα levels were significantly higher in patients with APS than healthy controls (median 2.95 pg/ml [range 0.51-10.75] vs. 0.95 pg/ml [0.51-1.6], respectively; p = 0.0001). Frequencies of TNFA-308*2 genotype did not differ between patients and controls. In contrast, TNFA-238*A positive genotype was more frequent in APS patients with arterial thrombosis and pregnancy loss than in controls (OR 3.7 [95% CI 1.37-10.1], p = 0.007 and OR 3.95 [95% CI 1.3-11.7], p = 0.01; respectively). DQB1*0303-DRB1*0701 haplotype was associated with TNFA-238*A in the control group (OR 96.0 [95% CI 9.6-959], p 0.0001) as well as in APS patient’s group (OR 54.2 [95% CI 9.6-306.5], p 0.0001). Conclusions. Raised plasma TNFα levels were found in patients with APS. As a prothrombotic and proinflammatory cytokine, TNFα may be involved in the development of clinical features of APS. The lack of correlation between the TNFA-238 polymorphism and plasma levels associated with disease suggests that the TNFα genetic marker may only indirectly relate to protein levels by virtue of allelic association with a functional marker which may reside in the HLA class II region.

Keywords

TNFA - thrombosis - HLA - Haplotype

Volltext

Referenzen

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