Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Functional Progression in Patients with Interstitial Lung Disease Resulted Positive to Antisynthetase Antibodies: A Multicenter, Retrospective Analysis.

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, "real life" study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline.

Non-specific interstitial pneumonia and features of connective tissue disease: What are the consequences of a different point of view?

Patients with Interstitial Lung Disease (ILD) without a definitive diagnosis of connective tissue diseases (CTD) were historically described as Undifferentiated Connective Tissue Disease (UCTD-ILD). Recently a new classification, Interstitial Pneumonia with Autoimmune Features (IPAF), has been proposed. Aim of this study was to describe the prevalence, clinical characteristics and prognostic factors of UCTD and IPAF subjects in a cohort of Non-Specific Interstitial Pneumonia (NSIP) patients. This retrospective, observational study enrolled 102 adult patients characterized by NSIP pattern on High Resolution Computed Tomography, without a specific diagnosis of CTD. Three groups were identified according to patients' characteristics: IPAF, UCTD or idiopathic NSIP (iNSIP). Forty percent, 27% and 55% of patients showed diagnostic criteria for IPAF, UCTD and iNSIP, respectively. No significant differences in age, gender, smoking habit, pulmonary function tests and three-year survival rate were observed among study groups. IPAF patients with antisynthetase antibodies positivity, in comparison to IPAF without antisynthetase antibodies positivity, showed more frequently an acute onset (44% vs 9%, p<0.012). The presence of autoimmune features seems not to be associated with better outcomes in NSIP patients. IPAF criteria seem to be more representative than UCTD criteria in identifying patients with autoimmune features. Further studies are needed to verify if IPAF should include patients with positive antisynthetase serology.