Institute of Laboratory Medicine, Unfallkrankenhaus Berlin, Berlin, Germany
Institute of Laboratory Medicine and Pathobiochemistry, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
RMD Open. 2021 Jun;7(2). doi: 10.1136/rmdopen-2021-001751.
Genetic determinants of fibrin clot formation and fibrinolysis have an impact on local and systemic inflammatory response. The aim of the present study was to assess whether coagulation-related genotypes affect the predictive value of C-reactive protein (CRP) in regards of radiographic spinal progression in axial spondyloarthritis (axSpA).
Two hundred and eight patients with axSpA from the German Spondyloarthritis Inception Cohort were characterised for genotypes of α-fibrinogen, β-fibrinogen (FGB) and γ-fibrinogen, factor XIII A-subunit (F13A) and α-antiplasmin (A2AP). The relation between CRP levels and radiographic spinal progression defined as worsening of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by ≥2 points over 2 years was assessed in dependence on the respective genetic background in logistic regression analyses.
Overall, CRP was associated with mSASSS progression ≥2 points: time-averaged CRP ≥10 mg/L, OR: 3.32, 95% CI 1.35 to 8.13. After stratification for coagulation-related genotypes, CRP was strongly associated with mSASSS progression in individuals predisposed to form loose, fibrinolysis-susceptible fibrin clots (FGB rs1800790GG, OR: 6.86, 95% CI 2.08 to 22.6; A2AP 6Trp, OR: 5.86, 95% CI 1.63 to 21.0; F13A 34Leu, OR: 8.72, 95% CI 1.69 to 45.1), while in genotypes predisposing to stable fibrin clots, the association was absent or weak (FGB rs1800790A, OR: 0.83, 95% CI 0.14 to 4.84; A2AP 6Arg/Arg, OR: 1.47, 95% CI 0.35 to 6.19; F13A 34Val/Val, OR: 1.72, 95% CI 0.52 to 5.71).
Elevated CRP levels seem to be clearly associated with radiographic spinal progression only if patients are predisposed for loose fibrin clots with high susceptibility to fibrinolysis.
纤维蛋白凝块形成和纤维蛋白溶解的遗传决定因素对局部和全身炎症反应有影响。本研究的目的是评估凝血相关基因型是否会影响 C 反应蛋白（CRP）对轴性脊柱关节炎（axSpA）放射学脊柱进展的预测价值。
从德国脊柱关节炎起始队列中选择 208 例 axSpA 患者，对其 α-纤维蛋白原、β-纤维蛋白原（FGB）和 γ-纤维蛋白原、因子 XIII A 亚单位（F13A）和 α2-抗纤溶酶（A2AP）的基因型进行特征分析。在逻辑回归分析中，根据各自的遗传背景，评估 CRP 水平与放射学脊柱进展之间的关系，放射学脊柱进展定义为改良 Stoke 强直性脊柱炎脊柱评分（mSASSS）在 2 年内增加≥2 分。
总体而言，CRP 与 mSASSS 进展≥2 分相关：时间平均 CRP≥10mg/L，OR：3.32，95%CI 1.35 至 8.13。在对凝血相关基因型进行分层后，在易形成疏松、纤维蛋白溶解敏感纤维蛋白凝块的个体中，CRP 与 mSASSS 进展密切相关（FGB rs1800790GG，OR：6.86，95%CI 2.08 至 22.6；A2AP 6Trp，OR：5.86，95%CI 1.63 至 21.0；F13A 34Leu，OR：8.72，95%CI 1.69 至 45.1），而在易形成稳定纤维蛋白凝块的基因型中，相关性缺失或较弱（FGB rs1800790A，OR：0.83，95%CI 0.14 至 4.84；A2AP 6Arg/Arg，OR：1.47，95%CI 0.35 至 6.19；F13A 34Val/Val，OR：1.72，95%CI 0.52 至 5.71）。
只有在患者易形成疏松、纤维蛋白溶解敏感性纤维蛋白凝块时，CRP 水平升高似乎与放射学脊柱进展明显相关。
