B35-30 From Cytopenias to Cysts: Early Sjogren’s Disease Revealed by Isolated Anti-Ro52 Positivity

Abstract Introduction Sjogren’s disease is heterogeneous with several distinct subgroups characterized by differences in interferon pathway activation, B cell activity, and inflammatory signatures. Isolated SS-A 52 kD (Ro52) antibody positivity is associated with an interferon-high endotype, which has been associated with interstitial lung disease (ILD). This often precedes sicca manifestations or classic serologic profiles. We present a novel case of lymphoid interstitial pneumonia (LIP) in a young adult with isolated anti-Ro52 positivity, immune thrombocytopenia (ITP), and a history of cerebral venous thrombosis, consistent with early extraglandular Sjogren’s disease. Case Report A 28-year-old trans man with ITP, prior cerebral venous sinus thrombosis complicated by hemorrhagic stroke, presented with several months of progressive fatigue, dyspnea, and new oxygen dependence. Computed tomography of the chest demonstrated diffuse ground-glass opacities, centrilobular nodules, subpleural consolidations, and scattered thin-walled cysts, consistent with LIP. Bronchoalveolar lavage revealed 81% monocytes, 18% lymphocytes, and no infectious organisms were isolated. The autoimmune workup was negative for antinuclear antibodies, anti-Ro60 (SS-A), anti-La (SS-B), rheumatoid factor, and anti-cyclic citrullinated peptide antibodies. HIV and hepatitis serologies were negative. Serum immunoglobulins were within normal limits. Lupus anticoagulant and antiphospholipid antibodies were negative. Vascular endothelial growth factor-D level was less than 250 pg/mL. The patient was initiated on prednisone 40 mg daily with a taper which resulted in improvement in symptoms and oxygenation. He was discharged on supplemental oxygen with plans for repeat imaging and close pulmonary follow-up. A myositis-specific (MyoMarker 3 plus) panel then revealed isolated Ro52 antibody positivity. Discussion This case represents a lung-dominant, type I interferon endotype of Sjogren’s disease manifesting before the onset of sicca symptoms or classical serologies. Ro52 functions as an E3 ubiquitin ligase regulating interferon signaling. Ro52 antibodies are associated with interferon pathway activation and are strongly linked to ILD, immune cytopenias, and systemic fatigue. They may appear in isolation and precede systemic features by years. In a retrospective study, anti-Ro52 seropositivity was associated with worse progression-free survival in patients with ILD. (1) Differentiating early Sjogren’s disease from undifferentiated connective tissue disease (UCTD) is challenging. While UCTD often presents with incomplete serologic profiles and nonspecific ILD, the presence of a constellation of anti-Ro52 with LIP, ITP and thrombosis supports a diagnosis of early Sjogren’s disease. References 1. Imai R, Bermea RS, Zhao SH, Montesi SB, Singh A, Flashner BM, et.al. Association of Anti-Ro52 Seropositive Interstitial Lung Disease With a Higher Risk of Disease Progression and Mortality. Chest. 2025 Oct;168(4):954-966. This abstract is funded by: None