Abstract：
Consistent correlation of serum amyloid A (SAA) to rheumatoid arthritis (RA) is not completely established. The present study is to systematically summarize their relationship.
Publications up to may 2021 were examined using key terms in the PubMed, Cochrane Library, Embase and China national knowledge infrastructure (CNKI) databases.
The total 33 studies, involving in 3524 RA cases and 3537 normal participants, were included. The pooled result indicated that the SAA level in the RA group was markedly higher than that in the control group [standardized mean difference (SMD) = 0.80, 95% CI (0.51, 1.08)]. By stratified analyses, the concentration of SAA was found to be gradually increased with the aggravation of RA. Additionally, the meta-analysis of correlation demonstrated that SAA levels were positively associated with the levels of disease activity score 28 (DAS28) [r = 0.55, 95% CI (0.15, 0.94)], erythrocyte sedimentation rate (ESR) [r = 0.65, 95% CI (0.53, 0.76)], C-reactive protein (CRP) [r = 0.92, 95% CI (0.57, 1.57)], rheumatoid factor (RF) [r = 0.24, 95% CI (0.09, 0.39)], interleukin 4 (IL-4) [r = 0.54, 95% CI (0.30, 0.78)], interleukin 6 (IL-6) [r = 0.46, 95% CI (0.27, 0.65)], interleukin 10 (IL-10) [r = 0.53, 95% CI (0.29, 0.77)], interleukin 17 (IL-17) [r = 0.52, 95% CI (0.27, 0.77)], and anti-cyclic citrullinated peptide antibody (A-CCP) [r = 0.32, 95% CI (0.15, 0.50)], but inversely linked with the levels of hemoglobin [r=-0.51, 95% CI (-0.84, -0.18)]. Furthermore, the allele of SAA 1.3 was actively related with increased risks of RA [OR=1.30, 95% CI (1.02, 1.65)] and of RA with amyloidosis [OR=2.06, 95% CI (1.63, 2.60)]. Besides, the genotype of SAA 1.3/1.3 was positively connected with the risks of RA [OR=1.56, 95% CI (1.00, 2.43)] and of RA with amyloidosis [OR=4.47, 95% CI (2.70, 7.41)].
High levels of SAA might be associated with elevated risk of RA, and the concentration of SAA might be gradually increased with the aggravation of RA. Moreover, high levels of SAA might play a vital role in RA by enhancing the levels of DAS28, ESR, CRP, RF, IL-4, IL-6, IL-10, IL-17 and A-CCP, or by attenuating hemoglobin levels. More importantly, the allele of SAA 1.3 and genotype of SAA 1.3/1.3 might be the risk factor of RA and of RA with amyloidosis.
Publications up to may 2021 were examined using key terms in the PubMed, Cochrane Library, Embase and China national knowledge infrastructure (CNKI) databases.
The total 33 studies, involving in 3524 RA cases and 3537 normal participants, were included. The pooled result indicated that the SAA level in the RA group was markedly higher than that in the control group [standardized mean difference (SMD) = 0.80, 95% CI (0.51, 1.08)]. By stratified analyses, the concentration of SAA was found to be gradually increased with the aggravation of RA. Additionally, the meta-analysis of correlation demonstrated that SAA levels were positively associated with the levels of disease activity score 28 (DAS28) [r = 0.55, 95% CI (0.15, 0.94)], erythrocyte sedimentation rate (ESR) [r = 0.65, 95% CI (0.53, 0.76)], C-reactive protein (CRP) [r = 0.92, 95% CI (0.57, 1.57)], rheumatoid factor (RF) [r = 0.24, 95% CI (0.09, 0.39)], interleukin 4 (IL-4) [r = 0.54, 95% CI (0.30, 0.78)], interleukin 6 (IL-6) [r = 0.46, 95% CI (0.27, 0.65)], interleukin 10 (IL-10) [r = 0.53, 95% CI (0.29, 0.77)], interleukin 17 (IL-17) [r = 0.52, 95% CI (0.27, 0.77)], and anti-cyclic citrullinated peptide antibody (A-CCP) [r = 0.32, 95% CI (0.15, 0.50)], but inversely linked with the levels of hemoglobin [r=-0.51, 95% CI (-0.84, -0.18)]. Furthermore, the allele of SAA 1.3 was actively related with increased risks of RA [OR=1.30, 95% CI (1.02, 1.65)] and of RA with amyloidosis [OR=2.06, 95% CI (1.63, 2.60)]. Besides, the genotype of SAA 1.3/1.3 was positively connected with the risks of RA [OR=1.56, 95% CI (1.00, 2.43)] and of RA with amyloidosis [OR=4.47, 95% CI (2.70, 7.41)].
High levels of SAA might be associated with elevated risk of RA, and the concentration of SAA might be gradually increased with the aggravation of RA. Moreover, high levels of SAA might play a vital role in RA by enhancing the levels of DAS28, ESR, CRP, RF, IL-4, IL-6, IL-10, IL-17 and A-CCP, or by attenuating hemoglobin levels. More importantly, the allele of SAA 1.3 and genotype of SAA 1.3/1.3 might be the risk factor of RA and of RA with amyloidosis.
摘要：
血清淀粉样蛋白A（SAA）与类风湿性关节炎（RA）的一致相关性尚未完全确定。本研究旨在系统地总结它们之间的关系。
截至2021年5月的出版物使用PubMed中的关键术语进行了审查，科克伦图书馆,Embase与中国国家知识基础设施(CNKI)数据库
总共33项研究，涉及3524例RA病例和3537例正常参与者，包括在内。合并结果表明，RA组的SAA水平明显高于对照组[标准化平均差异（SMD）=0.80，95％CI（0.51，1.08）]。通过分层分析，发现SAA的浓度随着RA的加重而逐渐增加。此外,相关性的荟萃分析表明，SAA水平与疾病活动评分28（DAS28）[r=0.55，95％CI（0.15，0.94）]水平呈正相关，红细胞沉降率(ESR)[r=0.65,95%CI(0.53,0.76)],C反应蛋白（CRP）[r=0.92，95%CI（0.57，1.57）]，类风湿因子（RF）[r=0.24，95%CI（0.09，0.39）]，白细胞介素4（IL-4）[r=0.54，95%CI（0.30，0.78）]，白细胞介素6（IL-6）[r=0.46，95%CI（0.27，0.65）]，白细胞介素10（IL-10）[r=0.53，95%CI（0.29，0.77）]，白细胞介素17（IL-17）[r=0.52，95%CI（0.27，0.77）]，和抗环瓜氨酸肽抗体（A-CCP）[r=0.32，95％CI（0.15，0.50）]，但与血红蛋白水平呈负相关[r=-0.51,95%CI(-0.84,-0.18)]。此外，SAA1.3的等位基因与RA[OR=1.30,95%CI(1.02,1.65)]和RA伴淀粉样变性[OR=2.06,95%CI(1.63,2.60)]的风险增加呈正相关.此外,SAA1.3/1.3基因型与RA[OR=1.56,95%CI(1.00,2.43)]和RA伴淀粉样变性[OR=4.47,95%CI(2.70,7.41)]的风险呈正相关.
高水平的SAA可能与RA风险升高有关，随着RA的加重，SAA的浓度可能逐渐升高。此外，高水平的SAA可能通过提高DAS28、ESR、CRP,射频,IL-4，IL-6，IL-10，IL-17和A-CCP，或通过降低血红蛋白水平。更重要的是,SAA1.3等位基因和SAA1.3/1.3基因型可能是RA和RA伴淀粉样变性的危险因素。
截至2021年5月的出版物使用PubMed中的关键术语进行了审查，科克伦图书馆,Embase与中国国家知识基础设施(CNKI)数据库
总共33项研究，涉及3524例RA病例和3537例正常参与者，包括在内。合并结果表明，RA组的SAA水平明显高于对照组[标准化平均差异（SMD）=0.80，95％CI（0.51，1.08）]。通过分层分析，发现SAA的浓度随着RA的加重而逐渐增加。此外,相关性的荟萃分析表明，SAA水平与疾病活动评分28（DAS28）[r=0.55，95％CI（0.15，0.94）]水平呈正相关，红细胞沉降率(ESR)[r=0.65,95%CI(0.53,0.76)],C反应蛋白（CRP）[r=0.92，95%CI（0.57，1.57）]，类风湿因子（RF）[r=0.24，95%CI（0.09，0.39）]，白细胞介素4（IL-4）[r=0.54，95%CI（0.30，0.78）]，白细胞介素6（IL-6）[r=0.46，95%CI（0.27，0.65）]，白细胞介素10（IL-10）[r=0.53，95%CI（0.29，0.77）]，白细胞介素17（IL-17）[r=0.52，95%CI（0.27，0.77）]，和抗环瓜氨酸肽抗体（A-CCP）[r=0.32，95％CI（0.15，0.50）]，但与血红蛋白水平呈负相关[r=-0.51,95%CI(-0.84,-0.18)]。此外，SAA1.3的等位基因与RA[OR=1.30,95%CI(1.02,1.65)]和RA伴淀粉样变性[OR=2.06,95%CI(1.63,2.60)]的风险增加呈正相关.此外,SAA1.3/1.3基因型与RA[OR=1.56,95%CI(1.00,2.43)]和RA伴淀粉样变性[OR=4.47,95%CI(2.70,7.41)]的风险呈正相关.
高水平的SAA可能与RA风险升高有关，随着RA的加重，SAA的浓度可能逐渐升高。此外，高水平的SAA可能通过提高DAS28、ESR、CRP,射频,IL-4，IL-6，IL-10，IL-17和A-CCP，或通过降低血红蛋白水平。更重要的是,SAA1.3等位基因和SAA1.3/1.3基因型可能是RA和RA伴淀粉样变性的危险因素。
