Relationship of serum osteoprotegerin with arterial stiffness, preclinical atherosclerosis, and disease activity in patients with ankylosing spondylitis

Objective.Epidemiological studies recently confirmed the increased risk of vascular morbidity and mortality during ankylosing spondylitis (AS). Increase of intima-media thickness (IMT) of the common carotid artery is a useful and noninvasive marker of preclinical atherosclerosis. The aim of our study was to compare IMT in patients with AS with matched controls and to determine risk factors of atherosclerosis related to AS.Methods.We performed a prospective study of 60 consecutive patients meeting modified New York criteria for AS, compared to 60 controls matched for age and sex. Disease-specific measures were determined. Measurement of IMT was performed by the same radiologist using the same machine and probe in right and left common carotid arteries, and the average of the 2 measurements was considered.Results.In total 48 male and 12 female patients were recruited, and 60 corresponding controls; mean age was 36 ± 11 years. We found significantly increased IMT in the AS group (0.51 ± 0.12 mm) compared with controls (0.39 ± 0.09 mm; p = 0.001). After adjustment for confounding factors, increased IMT was still present (p = 0.003). Age at onset of AS (p = 0.001), Bath AS Disease Activity Index (p = 0.002), AS Disease Activity Score (ASDAS) erythrocyte sedimentation rate (ESR; p = 0.047), ASDAS C-reactive protein (CRP; p = 0.012), Bath AS Functional Index (p = 0.008), global spine visual analog scale for pain (p = 0.000), Schober index (p = 0.039), Bath AS Metrology Index (p = 0.028), modified Stoke Ankylosing Spondylitis Spine Score (p = 0.035), and high ESR (p = 0.001) and CRP (p = 0.000) were correlated with high IMT in patients with AS. Otherwise, status of arthritis (p = 0.442), enthesitis (p = 0.482), and HLA-B27 (p = 0.528) seemed to have no effect on IMT.Conclusion.AS is associated with an increased risk of atherosclerosis independent of traditional risk factors. Disease activity, functional and mobility limitations, structural damage, and inflammation are the most incriminated risk factors.

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

The Journal of Rheumatology ◽

10.3899/jrheum.100019 ◽

2010 ◽

Vol 37 (9) ◽

pp. 1907-1910 ◽

Cited By ~ 37

Author(s):

NIGIL HAROON ◽

FLORENCE W.L. TSUI ◽

BASIL CHIU ◽

HING WO TSUI ◽

ROBERT D. INMAN

Keyword(s):

Endoplasmic Reticulum ◽

Ankylosing Spondylitis ◽

Disease Activity ◽

Cytokine Receptor ◽

Cytokine Receptors ◽

Serum Cytokine ◽

Markers Of Inflammation ◽

Significant Difference ◽

Cytokine Levels ◽

Relationship Of

Objective.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-6Rα, 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.Methods.Sera from patients with AS were assayed for TNF-α, IL-1, IL-6, sTNFRI, sIL-1RII, and sIL-6Rα 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.Results.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.Conclusion.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.

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