Pos0314 Anti-Neutrophil Cytoplasmic Antibodies Associated Interstitial Pneumonia: A New Clinical Entity?

Background: Pneumologists do not routinely include screening for anti-neutrophil cytoplasmic antibodies (ANCA) in the evaluation of interstitial pneumonia (IP). Indeed, antibodies against myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3) are not encompassed in the classification of IP with Autoimmune Features (IPAF), However, anti-MPO antibodies have been reported in subjects with ILD or idiopathic bronchiectasis (percentage ranging from 7 to 23%), but only a few studies describe their clinical evolution. Objectives: To evaluate the prevalence of anti-neutrophil cytoplasmic antibodies (ANCA), anti-MPO antibodies and anti-proteinase-3 (ant-PR3) antibodies in patients with Idiopathic pulmonary fibrosis (IPF) and IPAF in a pneumologist setting. Methods: We retrospectively collected clinical charts of patients referred to a Pneumology Clinic specialized in IP, who received a diagnosis of IPF/IPAF from 31 March 2018 to 1 April 2023. None of the patients had Connective Tissue Disease (CTD) or vasculitis signs/symptoms at diagnosis. We re-tested all patients for IPAF-associated autoantibodies (ANA, ENA, anti-CCP, RF) and ANCA, anti-MPO or ant-PR3. Descriptive statistics were performed for demographic and disease characteristics. Comparisons were carried out by chi-square or one-way ANOVA test. Analysis of outcome predictors was performed by logistic multiple logistic regression. To identify the clinical subset of IP patients with baseline features at higher odds to progress to systemic vasculitis, unsupervised clustering with K-means fitted with all baseline covariates was performed. Results: 103 patients were enrolled in the study whose demographics and clinical characteristics are showed in Table 1A. Of these, 37 patients were diagnosed with IPAF, and 64 with IPF. 21 patients were ANCA positive. We reclassified our patients into three groups: IP pANCA+ (n=21), IPF pANCA- (n=53), and IPAF pANCA- (n=27) (Table 1B). The IP pANCA+ group had a higher percentage of males (43%, p=0.04) and NSIP HRCT pattern (43%, p=0.02). At 6 and 12 months, IP pANCA+ patients showed higher frequency of bronchiectasis at 6 (71%, p=0.02) and 12 months (70%, p=0.04). None of the p-ANCA- patients developed vasculitis, but 29% and 38% of p-ANCA+ patients developed vasculitis at 6 and 12 months. No differences were observed in terms of HRTC progression, O2 therapy and death. Multiple regression models showed that disease duration was associated with HRCT progression (OR 1.28, p=0.03), smoke with death (OR 26.7, p=0.01), IPF with need of oxygen therapy (OR 6.33, p=0.04), ANCA positivity with the develop vasculitis (OR 1.22, p=0.04). None of the patients had full vasculitis at baseline, but some had extrapulmonary manifestations. Cluster analysis identified a subgroup of patients with higher odds to develop vasculitis (Figure 1). Conclusion: These findings suggest that in patients presenting with IP, testing for ANCAs should be performed routinely, as positive anti-MPO along with some systemic manifestation may identify a cluster of patients at high risk of vasculitis. Whether IP-ANCA+ disease should be considered a new pathological entity needs further investigation on prospective cohorts. REFERENCES: 1 Bridget A. Graney, Aryeh Fischer. Interstitial Pneumonia with Autoimmune Features. Ann Am Thorac Soc 2019, Vol 16, No 5, pp 525–533. 2 Sebastiani M, Manfredi A, Vacchi A, et al. Epidemiology and management of interstitial lung disease in ANCA-associated vasculitis. Clin Exp Rheumatol 2020; 38 (Suppl. 124): S221-S231. 3 Sebastiani M, Luppi F, Sambataro G, et al. Interstitial Lung Disease and Anti-Myeloperoxidase Antibodies: Not a Simple Association J. Clin. Med. 2021, 10, 2548 doi: 10.3390/jcm10122548. Acknowledgements: NIL. Disclosure of Interests: None declared.