title: A metaanalysis of the increased risk of rheumatoid arthritis-related pulmonary disease as a result of serum anticitrullinated protein antibody positivity.
abstract: OBJECTIVE
  An inconsistent association has been reported between the serum anticitrullinated protein antibodies (ACPA) level and rheumatoid arthritis (RA)-related pulmonary disease risk. We conducted a metaanalysis to reveal the association between them.
  
  
  METHODS
  An electronic search was performed in PubMed, ScienceDirect, and SpringerLink databases for studies published up to August 2013. The distributions of the serum ACPA level in cases and controls were obtained from eligible studies. The risk of RA-related pulmonary disease associated with serum ACPA positivity was estimated by OR and 95% CI. According to the heterogeneity results, a fixed-effects model or a random-effects model was used to calculate the pooled OR. Publication bias and sensitivity analyses were conducted.
  
  
  RESULTS
  Overall, 243 patients with RA-related pulmonary disease and 1442 RA controls were included in the metaanalysis. The results showed that the pooled OR was 2.621 (95% CI, 1.561-4.403, p < 0.001) for the increased risk of RA-related pulmonary disease due to the serum ACPA positivity. In the white population subgroup, an increased OR was 3.453 (95% CI 1.798-6.630, p < 0.001), whereas no association was found in the Asian population subgroup. Additionally, we further revealed that serum ACPA positivity indicated a higher risk for interstitial lung disease (ILD) and interstitial pulmonary fibrosis (IPF) among patients with RA (OR 4.679, 95% CI 2.071-10.572, p < 0.001). The heterogeneity, publication bias, and sensitivity analyses had no statistical significance in any group.
  
  
  CONCLUSIONS
  To our knowledge, this is the first metaanalysis to reveal that serum ACPA positivity is highly associated with the risk of RA-related pulmonary disease, particularly in RA-related ILD and IPF.
authors.affiliation: From the Department of Rheumatology, Nanfang Hospital, Southern Medical University; the Department of Internal Medicine of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Southern Medical University; the Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University; and the Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Department of Pathogen Biology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.J. Zhu, PhD; J. Li, MD, PhD, Department of Rheumatology, Nanfang Hospital, Southern Medical University, and Department of Internal Medicine of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Southern Medical University; Y. Zhou, MD, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University; X. Chen, MD, PhD, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Department of Pathogen Biology, School of Public Health and Tropical Medicine, Southern Medical University.
authors.forename: Junqing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: From the Department of Rheumatology, Nanfang Hospital, Southern Medical University; the Department of Internal Medicine of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Southern Medical University; the Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University; and the Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Department of Pathogen Biology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.J. Zhu, PhD; J. Li, MD, PhD, Department of Rheumatology, Nanfang Hospital, Southern Medical University, and Department of Internal Medicine of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Southern Medical University; Y. Zhou, MD, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University; X. Chen, MD, PhD, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Department of Pathogen Biology, School of Public Health and Tropical Medicine, Southern Medical University.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: From the Department of Rheumatology, Nanfang Hospital, Southern Medical University; the Department of Internal Medicine of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Southern Medical University; the Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University; and the Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Department of Pathogen Biology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.J. Zhu, PhD; J. Li, MD, PhD, Department of Rheumatology, Nanfang Hospital, Southern Medical University, and Department of Internal Medicine of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Southern Medical University; Y. Zhou, MD, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University; X. Chen, MD, PhD, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Department of Pathogen Biology, School of Public Health and Tropical Medicine, Southern Medical University.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
authors.affiliation: From the Department of Rheumatology, Nanfang Hospital, Southern Medical University; the Department of Internal Medicine of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Southern Medical University; the Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University; and the Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Department of Pathogen Biology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China.J. Zhu, PhD; J. Li, MD, PhD, Department of Rheumatology, Nanfang Hospital, Southern Medical University, and Department of Internal Medicine of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Southern Medical University; Y. Zhou, MD, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University; X. Chen, MD, PhD, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Department of Pathogen Biology, School of Public Health and Tropical Medicine, Southern Medical University. lj40038@126.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000097:blood / Q000209:etiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: ANTICITRULLINATED PROTEIN ANTIBODY; EXTRAARTICULAR MANIFESTATIONS; INTERSTITIAL LUNG DISEASE; INTERSTITIAL PULMONARY FIBROSIS; RHEUMATOID ARTHRITIS; RHEUMATOID ARTHRITIS-RELATED PULMONARY DISEASE