Serum Cytokine Receptors in Ankylosing Spondylitis: Relationship to Inflammatory Markers and Endoplasmic Reticulum Aminopeptidase Polymorphisms

• Published in: Journal of rheumatology Vol. 37; no. 9; pp. 1907 - 1910
• Main Authors: HAROON, Nigil, TSUI, Florence W. L, CHIU, Basil, HING WO TSUI, INMAN, Robert D
• Format: Journal Article
• Language: English
• Published: Toronto, ON Journal of Rheumatology Publishing 01-09-2010
• Subjects: Adult; Aminopeptidases - genetics; Aminopeptidases - metabolism; Biological and medical sciences; Biomarkers - blood; Cytokines - blood; Cytokines - genetics; Diseases of the osteoarticular system; Diseases of the spine; Female; Humans; Inflammation - blood; Inflammatory joint diseases; Isoenzymes - genetics; Isoenzymes - metabolism; Medical sciences; Middle Aged; Minor Histocompatibility Antigens; Polymorphism, Genetic; Receptors, Cytokine - blood; Receptors, Cytokine - genetics; Receptors, Cytokine - immunology; Severity of Illness Index; Spondylitis, Ankylosing - blood; Spondylitis, Ankylosing - genetics; Spondylitis, Ankylosing - immunology; ARTS-1; ERAP2; RECEPTOR SHEDDING; Diseases of the osteoarticular system; Cytokine; Rheumatology; Inflammatory joint disease; Inflammation; Spine disease; Spondylarthropathy; Chronic; Serum; Ankylosing spondylitis; Polymorphism; ERAPI
• ISSN: 0315-162X; 1499-2752; 1499-2752
• DOI: 10.3899/jrheum.100019

Endoplasmic reticulum aminopeptidase (ERAP)1 is associated with ankylosing spondylitis (AS) and is known to be involved in the clipping of the cytokine receptors interleukin 1 receptor II (IL-1RII), IL-6Ralpha, and tumor necrosis factor receptor I (TNFRI). We studied the relationship of these serum cytokine receptors and their corresponding cytokines to markers of inflammation and polymorphisms in ERAP1 and ERAP2 in patients with AS.
Sera from patients with AS were assayed for TNF-alpha, IL-1, IL-6, sTNFRI, sIL-1RII, and sIL-6Ralpha by ELISA. Genotyping was performed for 3 AS-associated nonsynonymous single-nucleotide polymorphisms in the ERAP1 gene [rs27044(C/G), rs10050860(C/T), and rs30187(C/T)] and 1 in the ERAP2 gene [rs2549782(T/G)]. The serum cytokine and receptor levels were compared between the different genotype groups and correlated to markers of inflammation and disease activity.
Eighty patients with AS (21 women) with a mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of 5.3 +/- 2.4 were enrolled. There was a significant correlation of sTNFRI with C-reactive protein (CRP; R = 0.43, p < 0.001) and erythrocyte sedimentation rate (ESR; R = 0.30, p = 0.01) but not with BASDAI. Serum cytokine levels were undetectable in the majority of patients. There was no significant difference in serum cytokines or the soluble receptors between patients with the different ERAP1/ERAP2 polymorphisms and their haplotypes. Similarly, there was no relationship of the polymorphisms with the serum cytokine levels nor the cytokine-receptor ratio.
Soluble TNFRI levels correlate with ESR and CRP in AS. The ERAP1 and ERAP2 polymorphisms associated with AS do not influence the serum cytokine receptor levels in patients with AS.