Serum anti-citrullinated protein antibodies and rheumatoid factor increase the risk of rheumatoid arthritis-related interstitial lung disease: a meta-analysis.
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).
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.
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.
ACPA and RF positive patients have greater risk of RA-ILD, and RA patients positive for ACPA should be paid more attention.
• Autoantibodies ACPA and RF increase the risk of RA-ILD. • Regions may be related to RA-ILD.
Xie S
，Li S
，Chen B
，Zhu Q
，Xu L
，Li F
... -
《-》
Factors associated with interstitial lung disease in patients with rheumatoid arthritis: A systematic review and meta-analysis.
Interstitial lung disease (ILD) is frequent in patients with rheumatoid arthritis (RA) and is a potentially life-threatening complication with significant morbidity and mortality. This meta-analysis aims to systematically determine the factors associated with the development of rheumatoid arthritis-related interstitial lung disease (RA-ILD).
All primary studies which reported the factors associated with of RA-ILD were eligible for the review except case reports. The Cochrane Library, PubMed, Embase, Web of Science, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), and WANFANG electronic databases were searched through to December 30, 2022, for studies investigating the factors associated with RA-ILD. The methodological quality assessment of the eligible studies was performed using the Newcastle-Ottawa Scale (NOS). 2 reviewers extracted relevant data independently. Then, weighed mean differences (WMDs) or pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were obtained for the relationships between the factors and RA-ILD. The statistical meta-analysis, subgroup and sensitivity analyses were performed using the Review Manager 5.3, and publication bias with Egger's test were performed using the Stata12.0 software.
A total of 22 articles were screened for a meta-analysis which involved 1887 RA-ILD patients and 8066 RA without ILD patients. Some identified factors that were associated with an increased risk of RA-ILD included male sex (OR = 1.92, 95% CI: 1.54-2.39; P < 0.00001), older age (WMD = 5.77 years, 95% CI: 3.50-8.04; P < 0.00001), longer duration of RA (WMD = 0.80 years, 95% CI 0.12-1.47; P = 0.02), older age at onset of RA (WMD = 6.41 years, 95% CI: 3.17-9.64; P = 0.0001), smoking (OR = 1.69, 95% CI: 1.30-2.18; P < 0.0001). Five factors of laboratory items associated with the development of RA-ILD were evaluated in the meta-analysis. Compared with RA without ILD patients, positive rheumatoid factor (RF) (OR = 1.72, 95% CI: 1.47-2.01; P < 0.00001) and positive anti-citrullinated protein antibodies (ACPA) (OR = 1.58, 95% CI: 1.31-1.90; P < 0.00001) increased the risk of RA-ILD. Meanwhile, RF titer (WMD = 183.62 (IU/mL), 95% CI: 66.94-300.30; P = 0.002) and ACPA titer (WMD = 194.18 (IU/mL), 95% CI: 115.89-272.47; P < 0.00001) were significantly associated with increased risk of RA-ILD. Elevated erythrocyte sedimentation rate (ESR) (WMD = 7.41 (mm/h), 95% CI: 2.21-12.61; P = 0.005) and C-reactive protein (CRP) (WMD = 4.98 (mg/L), 95% CI: 0.76-9.20; P = 0.02) were also significantly associated with the development of the RA-ILD, whereas antinuclear antibody (ANA) positive status was not significantly associated with increased risk of RA-ILD (OR = 1.27, 95% CI: 1.00-1.60; P = 0.05).
This meta-analysis showed that male gender, older age, longer duration of RA, older age at onset of RA, smoking, positive RF, positive ACPA, elevated RF titer, elevated ACPA titer, higher ESR and higher CRP were associated with RA-ILD.
Zhang M
，Yin J
，Zhang X
《PLoS One》
Serum rheumatoid factor IgA, anti-citrullinated peptide antibodies with secretory components, and anti-carbamylated protein antibodies associate with interstitial lung disease in rheumatoid arthritis.
Rheumatoid arthritis (RA) is often complicated with chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway disease, which occur as extra-articular manifestations. CLD in RA have been associated with the production of rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), or anti-carbamylated protein (CarP) antibody. However, few validation studies have been performed thus far. In the present study, we investigated the association of RF, ACPA, and anti-CarP antibodies with RA complicated with CLD.
Sera from RA patients with or without CLD were collected. The levels of serum RF, RF immunoglobulin A (IgA), ACPA IgG, ACPA IgA, and ACPA secretory component (SC) were measured using enzyme-linked immunosorbent assay.
The comparison of RA patients with and without CLD showed that RF IgA was associated with ILD (mean ± standard deviation: 206.6 ± 400.5 vs. 95.0 ± 523.1 U/ml, respectively, P = 1.13 × 10- 8), particularly usual interstitial pneumonia (UIP) (263.5 ± 502.0 U/ml, P = 1.00 × 10- 7). ACPA SC was associated with RA complicated with ILD (mean ± standard deviation: 8.6 ± 25.1 vs. 2.3 ± 3.4 U/ml, respectively, P = 0.0003), particularly nonspecific interstitial pneumonia (NSIP) (10.7 ± 31.5 U/ml, P = 0.0017). Anti-CarP antibodies were associated with RA complicated with ILD (0.042 ± 0.285 vs. 0.003 ± 0.011 U/ml, respectively, P = 1.04X10- 11).
RF IgA and ACPA SC in RA were associated with UIP and NSIP, respectively, suggesting different specificities in patients with RA. Anti-CarP antibodies were associated with ILD in RA. These results may help elucidate the different pathogeneses of UIP and NSIP in RA.
Oka S
，Higuchi T
，Furukawa H
，Shimada K
，Okamoto A
，Hashimoto A
，Komiya A
，Saisho K
，Yoshikawa N
，Katayama M
，Matsui T
，Fukui N
，Migita K
，Tohma S
... -
《BMC MUSCULOSKELETAL DISORDERS》
Only rheumatoid factor-positive subset of anti-citrullinated peptide/protein antibody-negative rheumatoid arthritis may seroconvert to anti-citrullinated peptide/protein antibody-positive.
Anti-citrullinated peptide/protein antibody (ACPA) has been reported to occur in about 60% of patients with early rheumatoid arthritis (RA), and about 80% in patients with established RA. While ACPA seroconversion is possible, previous reports have shown that it rarely occurs. We retrospectively determined the proportion of patients who underwent ACPA seroconversion and described the clinical characteristics of these cases.
ACPA-negative RA patients who had undergone ACPA assessment more than once with an interval of 3 months or longer were investigated for ACPA seroconversion. The clinical characteristics of seroconverted patients were assessed.
In 149 ACPA-negative RA patients, only eight patients (5.4%) converted to ACPA-positive during follow-up. We found that all eight of the seroconverted cases were positive for rheumatoid factor (RF) and showed bone erosions by X-ray. Of 56 ACPA-negative RF-positive RA patients, 14.3% of them seroconverted to ACPA-positive. None of the ACPA-negative RF-negative RA patients seroconverted to ACPA-positive.
The proportion of total RA patients who experienced seroconversion from ACPA-negative to ACPA-positive was 5.4%. When ACPA-negative RA patients were subdivided into RF-negative and RF-positive subsets, only the RF-positive subset seroconverted to ACPA-positive. These results imply that RF-negative and RF-positive patients are distinct subsets within ACPA-negative RA patients.
Hiwa R
，Ohmura K
，Nakabo S
，Terao C
，Murakami K
，Nakashima R
，Imura Y
，Yukawa N
，Yoshifuji H
，Hashimoto M
，Furu M
，Ito H
，Fujii T
，Mimori T
... -
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ResearchGate
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