Ally Mahmood M T M, Hodkinson Bridget, Meyer Pieter W A, Musenge Eustasius, Tintinger Gregory R, Tikly Mohammed, Anderson Ronald
Department of Internal Medicine Faculty of Health Sciences, University of Pretoria, Bophelo Road, Private Bag X663, Pretoria, 0001, South Africa.
Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Bophelo Road, Pretoria, 0001, South Africa.
BMC Musculoskelet Disord. 2015 May 29;16:130. doi: 10.1186/s12891-015-0587-1.
To measure circulating anti-citrullinated peptide antibodies (ACPA) and cytokines pre- and 6 months post-therapy as a strategy to predict and optimize responses to traditional disease-modifying antirheumatic drugs (DMARDs) in early RA, which is an unmet need in developing countries.
A cohort of 140 predominantly (88.5 %) black female South African patients with early RA was treated with synthetic DMARDs, mostly methotrexate (MTX) alone, or in combination with low-dose oral corticosteroids (CS). Circulating ACPA and a panel of circulating cytokines/chemokines/growth factors were measured at baseline and after 6 months of therapy in relation to disease activity and Shared Epitope (SE).
Following 6 months of therapy, the median simplified disease activity index (SDAI) declined from a baseline of 41.4 to 16.0 (p = 0.0001) for the entire cohort, which was paralleled by significant falls in median serum ACPA levels (516.6 vs. 255.7 units/ml, p = <0.0001) and several of the circulating cytokines (IL-4, IL-7, IL-8, G-CSF, VEGF; p < 0.0010 - p < 0.0001) which were most evident in the subgroup of patients treated with a combination of MTX and CS. Although biomarker concentrations decreased most notably in the low-disease activity group post-therapy, no significant correlations between these biomarkers and disease activity were observed, Baseline ACPA levels, but not SDAI or cytokines, were significantly higher in the subgroup of risk allele-positive patients (561.1 vs. 331.9 units/ml, p < 0.05), while no associations with ACPA and a smoking history were evident.
The use of DMARDs in RA is associated with significant decreases in ACPA and cytokines which did not correlate with changes in SDAI, precluding the utility of serial measurement of these biomarkers to monitor early responses to therapy, but may have prognostic value.
在发展中国家，测量治疗前及治疗后6个月的循环抗瓜氨酸化肽抗体（ACPA）和细胞因子，作为预测和优化早期类风湿关节炎（RA）患者对传统改善病情抗风湿药物（DMARDs）反应的一种策略，这是一个尚未满足的需求。
对140例主要为（88.5%）黑人女性的南非早期RA患者组成的队列进行治疗，使用合成DMARDs，大多单独使用甲氨蝶呤（MTX），或与低剂量口服糖皮质激素（CS）联合使用。在基线及治疗6个月后，测量循环ACPA以及一组循环细胞因子/趋化因子/生长因子，并与疾病活动度和共同表位（SE）相关联。
治疗6个月后，整个队列的简化疾病活动指数（SDAI）中位数从基线的41.4降至16.0（p = 0.0001），同时血清ACPA水平中位数显著下降（516.6对255.7单位/毫升，p = <0.0001），并且几种循环细胞因子（IL-4、IL-7、IL-8、G-CSF、VEGF；p < 0.0010 - p < 0.0001）也显著下降，这在接受MTX与CS联合治疗的患者亚组中最为明显。尽管治疗后生物标志物浓度在低疾病活动度组下降最为显著，但未观察到这些生物标志物与疾病活动度之间存在显著相关性。风险等位基因阳性患者亚组的基线ACPA水平显著更高（561.1对331.9单位/毫升，p < 0.05），而SDAI或细胞因子则不然，同时未发现ACPA与吸烟史之间存在关联。
在RA中使用DMARDs与ACPA和细胞因子显著下降相关，而这些下降与SDAI的变化无关，这排除了通过连续测量这些生物标志物来监测治疗早期反应的实用性，但可能具有预后价值。
