Ab0247 a Monocentric Cohort Analysis of Patients With Idiopathic Inflammatory Myositis Without Myositis-Specific and Associated Autoantibodies

Background: Serum autoantibodies constitute the major biomarker of inflammatory myositis and have consistently served as a model for precision medicine by predicting clinical features and trajectories. To underscore this concept, inflammatory myositis are classified based on the positivity of different myositis-specific (MSA) and -associated (MAA) antibodies, but can also be diagnosed in the absence of MSA/MAA, thus requiring further research to delineate the clinical spectrum of seronegative myositis. Objectives: To analyse demographic, clinical and immunological features of patients with idiopathic inflammatory myositis without myositis-specific and associated autoantibodies, belonging to a monocentric cohort. Methods: A retrospective analysis was conducted on a cohort of 87 patients with inflammatory myositis followed in our Unit, with a focus on demographic, clinical, and serological features. Antinuclear antibodies (ANA) were tested on HEp-2 slides by an expert biologist following standard references. Seronegative IIM was defined if no connective tissue disease-related antibody (including MSA/MAA) could be identified using standard techniques together with RNA- and protein-immunoprecipitation. Results: Out of 87 patients, 18 were seronegative (21%), with a slight predominance of male subjects (19% vs 39%). Other demographic features, as well as cancer incidence, were equally distributed among seropositive and seronegative IIM patients. Notably, muscle involvement was significantly more common among seronegative subjects (100%) compared to the seropositive counterpart (71%; p = 0.009), while interstitial lung disease (ILD) was less common in the seronegative group compared to the seropositive subset (22% vs. 51%; p = 0.044). Nevertheless, the proportion of patients with a fibrotic ILD phenotype did not differ between the two subgroups. Clinical features suggestive of dermatomyositis, as well as Raynaud's phenomenon, calcinosis, arthritis, and myocarditis, oropharyngeal dysphagia were equally distributed between the two groups. Considering the whole cohort, HEp-2 ANA immunofluorescence results were available for 86 (99%) patients, with 15/86 (17%) being ANA-negative, while nuclear staining was reported in 53/71 (75%), cytoplasmic staining in 23/71 (32%), and nucleolar staining in 15/71 (21%) IIM patients. ANA-negative IIM patients had more frequently clinical evidence of myositis (80% vs 60%; p = 0.09), while Gottron's sign was less frequent in this subset (31% vs 60%; p = 0.03), and lymphopenia at diagnosis was observed only in ANA-positive inflammatory myositis patients (21/46, 46% vs 0/7, 0%; p = 0.02). Notably, ANA-negative subjects showed a significantly higher prevalence of anti-MDA5 antibodies (2/15, 13%, vs 1/71, 1%; p = 0.02). Conclusion: Seronegative inflammatory myositis represents one-fifth of our cohort and is characterized by high prevalence of skeletal muscle involvement, but less pulmonary disease, compared to the seropositive counterpart. Typical signs suggestive of a 'type I interferon signature' (e.g., Gottron's, lymphopenia) are absent in ANA-negative inflammatory myositis, and this observation needs confirmation in larger datasets, with immunological studies particularly on type I interferons while we cannot rule out the possibility that muscle involvement is deemed necessary for the diagnosis of seronegative cases. REFERENCES: 1 Ceribelli A, et al. Front Med (Lausanne) 2023; Tonutti A, at al. Front Immunol 2022; Ceribelli A, et al. J Transl Autoimmun 2020; Ceribelli A, et al. Clin Rheumatol 2017. Acknowledgements: NIL. Disclosure of Interests: Antonio Tonutti: None declared, Natasa Isailovic: None declared, Maria De Santis: None declared, Carlo Selmi Consulting/ speakers fee (AbbVie, Amgen, Alfa-Sigma, Biogen, Eli-Lilly, EUSA Pharma - Recordati, Galapagos, Janssen, Novartis, Octapharma, Pfizer, Recordati Rare Disease, SOBI), Research support (AbbVie, Amgen, Janssen, Novartis, Pfizer), Angela Ceribelli: None declared.