The objective was to identify immune alterations in patients with fibromyalgia syndrome (FMS) compared to healthy controls (HC) using meta-analysis and meta-regression. Six electronic databases were searched for suitable original articles investigating immune biomarkers in FMS in comparison to HC. We extracted outcomes and variables of interest, such as mean and SD of peripheral blood immune biomarkers, age or sex. A random-effects model with restricted maximum-likelihood estimator was used to compute effect sizes (standardized mean difference and 95% CI, Hedges' g) and meta-analysis, group meta-analysis and meta-regressions were conducted. Forty-three papers were included in this systematic review, of which 29 were suitable for meta-analysis. Interleukin (IL)-6 (g=0.36 (0.09-0.63); I2=85.94; p=0.01), IL-4 (g=0.50 (0.03-0.98); I2=81.87; p=0.04), and IL-17A (g=0.53 (0.00-1.06); I2=87.15; p=0.05), were significantly higher in FMS compared to HC while also combinations of cytokines into relevant phenotypes were significantly upregulated including M1 macrophage (g=0.23 (0.03-0.43); I2=77.62; p=0.02), and immune-regulatory (g=0.40 (0.09-0.72); I2=84.81; p=0.01) phenotypes. Heterogeneity levels were very high and subgroup and meta-regression analyses showed that many covariates explained part of the heterogeneity including medication washout, sex, time of blood sampling and exclusion of patients with major depressive disorder. In conclusion, FMS is accompanied by a disbalance between upregulated pro-inflammatory (M1 and Th-17) and immune-regulatory cytokines although effect sizes are small-to-moderate. Based on our results we provide specific methodological suggestions for future research, which should assess Th-1, Th-17, chemokines, and Th-2 phenotypes while controlling for possible confounding variables specified in this study.

中文翻译：

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纤维肌痛中的外周免疫异常：系统评价、荟萃分析和荟萃回归

目的是使用荟萃分析和荟萃回归确定纤维肌痛综合征 (FMS) 患者与健康对照 (HC) 相比的免疫改变。在六个电子数据库中搜索了合适的原始文章，这些文章研究了 FMS 中的免疫生物标志物与 HC 的比较。我们提取了感兴趣的结果和变量，例如外周血免疫生物标志物的平均值和标准差、年龄或性别。使用具有受限最大似然估计量的随机效应模型来计算效应大小（标准化平均差和 95% CI，Hedges' g），并进行了荟萃分析、组荟萃分析和荟萃回归。本次系统评价共收录 43 篇论文，其中 29 篇适合进行荟萃分析。白细胞介素 (IL)-6 (g=0.36 (0.09-0.63)；I2=85.94；p=0.01)、IL-4 (g=0.50 (0.03-0.98)；I2=81.87；p=0。04) 和 IL-17A (g=0.53 (0.00-1.06); I2=87.15; p=0.05)，与 HC 相比，在 FMS 中显着更高，同时细胞因子与相关表型的组合也显着上调，包括 M1 巨噬细胞 (g =0.23 (0.03-0.43)；I2=77.62；p=0.02) 和免疫调节 (g=0.40 (0.09-0.72)；I2=84.81；p=0.01) 表型。异质性水平非常高，亚组和元回归分析表明，许多协变量解释了部分异质性，包括药物洗脱、性别、采血时间和排除重度抑郁症患者。总之，FMS 伴随着上调的促炎细胞因子（M1 和 Th-17）和免疫调节细胞因子之间的失衡，尽管效应大小是小到中等。根据我们的结果，我们为未来的研究提供了具体的方法论建议，