Systematic review and meta-analysis of clinical significance of autoantibodies for idiopathic pulmonary fibrosis

OBJECTIVE: To clarify clinical significance of the sole presence of autoantibodies for idiopathic pulmonary fibrosis (IPF) without any other symptoms or signs suggestive of autoimmune disease. DESIGN: Systematic review and meta-analysis DATA SOURCES: Medline, EMBASE, Science Citation Index Expanded and Google Scholar were searched from 1 January 2002 through 12 February 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Primary studies addressing all-cause mortality and the development of a defined autoimmune disease for IPF with autoantibodies were included for the review. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted relevant data and assessed risk of bias independently. Meta-analysis was conducted using a random-effects model if three or more studies reported the same outcome for a certain autoantibody. The quality of evidence was assessed by the Grades of Recommendation, Assessment, Development and Evaluation system. RESULTS: Out of 4603 records retrieved nine studies were included in this review. All studies contained some risk of bias. Based on pooled data myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) was significantly associated with microscopic polyangiitis incidence with risk ratio (RR) of 20.2 (95% CI: 7.22 to 56.4) and antinuclear antibody (ANA) was also significantly associated with the development of connective tissue diseases with RR of 7.11 (p=0.001) (10 cases in 157 patients with ANA) in one study. However, there was no significant association of autoantibodies with all-cause mortality aside from MPO-ANCA and proteinase 3-ANCA in one study each. MPO-ANCA was not demonstrated to be associated with all-cause mortality by meta-analysis. The quality of evidence was deemed as either low or very low. CONCLUSIONS: The presence of autoantibodies such as MPO-ANCA and ANA was demonstrated to be associated with the development of some autoimmune diseases for patients with IPF although there was no difference of all-cause mortality. However, the results should be interpreted with caution due to low evidence level. PROSPERO REGISTRATION NUMBER: CRD42017077336.