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Meta-Analysis
. 2021 Nov;40(11):4533-4543.
doi: 10.1007/s10067-021-05808-2. Epub 2021 Jun 29.

Serum anti-citrullinated protein antibodies and rheumatoid factor increase the risk of rheumatoid arthritis-related interstitial lung disease: a meta-analysis

Sisi Xie  1 , Shu Li  1 , Bilin Chen  1 , Qing Zhu  1 , Lichang Xu  2 , Fen Li  3
Affiliations
Meta-Analysis

Serum anti-citrullinated protein antibodies and rheumatoid factor increase the risk of rheumatoid arthritis-related interstitial lung disease: a meta-analysis

Sisi Xie et al. Clin Rheumatol. 2021 Nov.

Abstract

Background: This meta-analysis aims to determine the association between antibodies including anti-citrullinated protein antibodies (ACPA) and rheumatoid factors (RF) and risk of rheumatoid arthritis-related interstitial lung disease (RA-ILD).

Methods: PubMed, Embase, and Cochrane were searched up to September 13, 2020, for studies investigating the risk of RA-ILD in ACPA-positive patients. The statistical meta-analysis and sensitivity analysis were performed using the Review Manager 5.4 and Stata16.0 software, respectively.

Results: Total 1 double-blind randomized controlled study and 16 observational studies, including 992 RA-ILD patients and 2223 RA-non ILD patients, met the inclusion criteria of the meta-analysis. Compared with ACPA-negative patients, positive serum ACPA increased the risk of RA-ILD (OR = 2.51; 95% CI: 1.35-4.68; P = 0.004) and serum ACPA titer was significantly correlated with risk of RA-ILD (SMD = 0.39; 95% CI: 0.17-0.62; P = 0.0006). In a region-based subgroup analysis, ACPA titer in Asian, European, and African populations was significantly related to the risk of RA-ILD, while there was no significant correlation in the Americans (SMD = - 0.03; 95% CI: - 0.89-0.83; P = 0.95), especially in the USA (SMD = 0.37; 95% CI: - 0.26-0.99; P = 0.25). In addition, serum positive RF increased the risk of RA-ILD (OR = 2.85; 95% CI: 2.19-3.71; P < 0.00001) and serum RF titer was significantly correlated with the risk of RA-ILD (SMD = 0.35; 95% CI: 0.23-0.46; P < 0.00001). However, for the analysis of RF dichotomous data, the funnel shape was asymmetric and the p value of egger test was less than 0.05, which indicated potential publication bias.

Conclusions: ACPA and RF positive patients have greater risk of RA-ILD, and RA patients positive for ACPA should be paid more attention.

Key points: • Autoantibodies ACPA and RF increase the risk of RA-ILD. • Regions may be related to RA-ILD.

Keywords: Anti-citrullinated protein antibody; Meta-analysis; Rheumatoid arthritis–related interstitial lung disease; Rheumatoid factor.

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References

    1. Huizinga TW, Pincus T (2010) In the clinic. Rheumatoid arthritis. Annals of internal medicine 153 (1):ITC1–1-ITC1–15; quiz ITC11–16. https://doi.org/10.7326/0003-4819-153-1-201007060-01001
    1. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovský J, Wolfe F, Hawker G (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581. https://doi.org/10.1002/art.27584 - DOI - PubMed - PMC
    1. Demoruelle MK, Parish MC, Derber LA, Kolfenbach JR, Hughes-Austin JM, Weisman MH, Gilliland W, Edison JD, Buckner JH, Mikuls TR, O’Dell JR, Keating RM, Gregersen PK, Norris JM, Holers VM, Deane KD (2013) Performance of anti-cyclic citrullinated peptide assays differs in subjects at increased risk of rheumatoid arthritis and subjects with established disease. Arthritis Rheum 65(9):2243–2252. https://doi.org/10.1002/art.38017 - DOI - PubMed - PMC
    1. Tsuchiya Y, Takayanagi N, Sugiura H, Miyahara Y, Tokunaga D, Kawabata Y, Sugita Y (2011) Lung diseases directly associated with rheumatoid arthritis and their relationship to outcome. Eur Respir J 37(6):1411–1417. https://doi.org/10.1183/09031936.00019210 - DOI - PubMed
    1. Lee DM, Schur PH (2003) Clinical utility of the anti-CCP assay in patients with rheumatic diseases. Ann Rheum Dis 62(9):870–874. https://doi.org/10.1136/ard.62.9.870 - DOI - PubMed - PMC

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