Association of anti-Ro52 autoantibody with interstitial lung disease in autoimmune diseases: a systematic review and meta-analysis

Objectives Interstitial lung disease (ILD) is an important manifestation of autoimmune diseases that can lead to morbidity and mortality. Although several autoantibodies have been linked with ILD presentation and adverse outcomes, the association of anti-Ro52 antibody with ILD is less studied. Hence, we investigated this association in various autoimmune diseases in the current study. Design We designed a systematic review and meta-analysis and did a comprehensive search from inception until 2 January 2023. Data sources A systematic search was conducted in four electronic databases: PubMed, Web of Science, Scopus and Embase. Eligibility criteria Observational studies that reported ILD diagnosis (outcome) and anti-Ro antibody (exposure) status in any autoimmune conditions (population) were included. The association between rapidly progressive ILD (RP-ILD) and anti-Ro52 was studied in idiopathic inflammatory myopathies (IIM). Data extraction and synthesis Collected data included study characteristics and ORs with 95% CIs. Quality assessment was performed using a modified version of the Newcastle-Ottawa Scale for cross-sectional studies. Random effects meta-analysis was used to pool the effect estimates. Results A total of 2353 studies were identified, from which 59 articles met the eligibility criteria. Anti-Ro52/SSA positivity was associated with ILD in all autoimmune disease subgroups: IIM (OR=3.08; 95% CI: 2.18 to 4.35; p value<0.001; I 2 =49%), systemic lupus (OR=2.43; 95% CI: 1.02 to 5.79; p=0.046; I 2 =71%), Sjogren (OR=1.77; 95% CI: 1.09 to 2.87; p=0.021; I 2 =73%), systemic sclerosis (OR=1.71; 95% CI: 1.04 to 2.83; p=0.036; I 2 =43%), mixed connective tissue disease (OR=3.34; 95% CI: 1.82 to 6.13; p<0.001; I 2 =0%). Additionally, anti-Ro52-positive myopathy patients were more likely to have simultaneous RP-ILD (OR=2.69; 95% CI:1.50 to 4.83; p<0.001; I 2 =71%). Conclusion Anti-Ro52/SSA positivity is associated with a higher frequency of ILD diagnosis in various autoimmune diseases. Anti-Ro52/SSA is also linked with a more severe lung involvement (RP-ILD). Future studies can investigate the benefits of screening for anti-Ro52 and its association with ILD development. PROSPERO registration number CRD42022381447.