Association between serum amyloid A and rheumatoid arthritis: A systematic review and meta-analysis

Backgrounds: Consistent correlation of serum amyloid A (SAA) to rheumatoid arthritis (RA) is not completely established. The present study is to systematically summarize their relationship. Methods: Publications up to may 2021 were examined using key terms in the PubMed, Cochrane Library, Embase and China national knowledge infrastructure (CNKI) databases. Results: 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)]. Conclusions: 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. (c) 2021 Elsevier Inc. All rights reserved.