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

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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.

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Funding

This study was funded by the Hunan Provincial Health Committee 225 Talent Project and funded by the Project of Changsha Science and Technology Bureau, kq1901119.

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Sisi Xie, Shu Li, Bilin Chen, Qing Zhu & Fen Li

  2. Department of Computer Science, University of California Santa Cruz, Santa Cruz, CA, 95064, USA

    Lichang Xu

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  1. Sisi Xie
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  2. Shu Li
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  4. Qing Zhu
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Contributions

FL and SSX conceived and designed the study. BLC and QZ conducted the literature search. SL and LCX conducted the data extraction. SSX conducted meta-analysis and interpreted the data. SSX and SL wrote the draft of the manuscript. FL and SSX critically revised the manuscript. All authors approved submission of the final version of the manuscript.

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Correspondence to Fen Li.

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This article does not contain any studies with human participants performed by any of the authors.

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Sisi Xie and Shu Li1 are co-first authors.

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Xie, S., Li, S., Chen, B. et al. Serum anti-citrullinated protein antibodies and rheumatoid factor increase the risk of rheumatoid arthritis–related interstitial lung disease: a meta-analysis. Clin Rheumatol 40, 4533–4543 (2021). https://doi.org/10.1007/s10067-021-05808-2

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