ANTI-TH/TO POSITIVITY IN SYSTEMIC SCLEROSIS: ANALYSIS OF PULMONARY INVOLVEMENT, ORGAN DAMAGE ACCRUAL AND MORTALITY IN AN ITALIAN MONOCENTRIC COHORT

Background: Anti-Th/To antibodies, detected in 2-5% Systemic Sclerosis (SSc) patients, are associated to interstitial lung disease (ILD) in half of the cases. However, long-term data on ILD as well as on organ damage accrual are lacking. Objectives: To describe the clinical associations of anti-Th/To SSc patients, focusing on ILD, organ damage and mortality. Methods: Monocentric retrospective study. 1) Description of clinical associations of anti-Th/To SSc patients (2013 ACR/EULAR criteria). 2) Case-control study: anti-Th/To vs anti-Topoisomerase (anti-Topo)1 patients (1:3; matched for sex and age at SSc onset) regarding a) ILD b) organ damage c) survival. ILD progression was assessed through pulmonary function tests (PFTs) at baseline (T0) and after 1 (T1), 5 (T5), 10 (T10) and 20 (T20) years. Organ damage was evaluated with SCTD-Damage Index (SCTD-DI) . Continuous data are expressed as median [IQR]. Results: We identified 13 anti-Th/To patients (all Caucasians, F/M=10/3, median age at SSc onset: 50 [37-67] years). Anti-Th/To were assayed by RNA immunoprecipitation in 8/13 and by immunoblotting in 5/13 cases. 1) 2/13 patients had SSc/myositis overlap syndrome: 1 associated to anti-SRP, 1 negative for myositis specific antibodies and affected by a synchronous (±3 years from onset) cancer. All presented lcSSc, 77% esophageal symptoms, 46% digital ulcers (DUs), 40% ILD, 39% telangiectasias, 39% heart involvement (3 pericarditis, 1 myocarditis in patient anti-SRP+, 1 arrhythmia), 15% gastrointestinal symptoms, 15% myositis and 8% calcinosis. No patients presented synovitis, joint contractures, pulmonary arterial hypertension nor scleroderma renal crisis. 2a) Anti-Th/To ILD patients, as compared to 39 anti-Topo 1, less frequently required immunosuppression and never required antifibrotic or O 2 therapy ( Table 1 ); ILD progression (%pFVC decline ≥10% or %pFVC decline 5-10% and %pDLCO decline ≥15%) was shown for 3/13, albeit, after a longer interval than in 8/39 anti-Topo 1 progressors (15 [10-15] vs 1 [1-6.3] years, p:0.05); none died because of ILD. Table 1. anti-Th/To+ n=13 anti-Topo 1+ n=39 p-value ILD on HRTC 4/10 (40) 28/33 (85) 0.01 Immunosuppressants 1/13 (8) 16/39 (41) 0.04 Antifibrotic and/or O 2 0/13 (0) 8/39 (21) 0.18 PH secondary to ILD 0/13 (0) 6/39 (15) 0.32 SSc-ILD related death 0/13 (0) 6/39 (15) 0.32 %pFVC T0 105 [85-114] 90 [81-114] 0.26 %pFVC T1 107 [97-112] 88 [80-108] 0.09 %pFVC T5 97 [84-114] 99 [83-111] 0.88 %pFVC T10 103 [91-114] 88 [80-112] 0.23 %pFVC T20 104 [83-111] 81 [74-103] 0.35 %pFVC <70% T0 0/13 (0) 3/39 (8) 0.56 %pFVC <70% T1 0/12 (0) 3/39 (8) 1.00 %pFVC <70% T5 0/10 (0) 3/33 (9) 1.00 %pFVC <70% T10 0/7 (0) 3/25 (12) 1.00 %pFVC <70% T20 0/5 (0) 1/8 (13) 1.00 Progressive fibrosis (PF)* [T1-T0] 0/12 (0) 5/39 (13) 0.32 PF* [T5-T0] 1/10 (10) 5/33 (15) 1.00 PF* [T10-T0] 1/7 (14) 4/25 (16) 1.00 PF* [T20-T0] 2/5 (40) 0/8 (0) 0.20 Continuous data are presented as median [IQR] and compared with Mann-Whitney test; categorical data are presented as number/number available data (%) and compared with Chi-square test/Fisher’s exact test. *Progressive fibrosis= %pFVC decline ≥10% or 5-10% %pFVC decline and %pDLCO decline ≥15%. 2b) During 16 [6-20] years of follow-up, SCTD-DI score progressively increased, but remained low in all patients (SCTD-DI ≤5) and was significantly lower than in anti-Topo 1 ( Figure 1 a ), mainly due to ILD, joint contractures and DUs in the latter group (85% vs 40%, p:0.01; 39% vs 0%, p:0.01; 77% vs 46%, p:0.08). Figure 1. 2c) 4/13 patients died at 81 [75-86] years after 10 [8-13] years of disease duration, none due to SSc. The survival curves of the two groups are showed in Figure 1 b . Conclusion: In this cohort anti-Th/To patients showed a mild SSc phenotype, characterized by lower organ damage, more favorable long-term ILD functional outcome (although detectable in 40% of patients) and higher survival, as compared to matched anti-Topo 1 patients. Larger multicenter studies are needed to confirm these data. REFERENCES: [1]Stochmal A. Clinic Rev Allerg Immunol. 2019. Ferdowsky N. Ann Rheum Dis. 2018. Disclosure of Interests: None declared Citation: , volume 81, supplement 1, year 2022, page 1475Session: Scleroderma, myositis and related syndromes (Publication Only)