Novel UNC93B1 variant causes rheumatoid arthritis and interstitial pneumonia

Tingyan He^1*Junbin Ou²Lijuan Huang²Xinyi Zhou²Linlin Wang¹Xiaolin Li²Yang Jun¹

• ¹Shenzhen Children's Hospital, Shenzhen, China
• ²Boai Hospital of Zhongshan, Zhongshan, China

Background: UNC93B1 is a transmembrane protein essential for regulating toll-like receptors (TLRs). Human UNC93B1 pathogenic variants have been recently described in limited patients with childhood systemic lupus erythematosus and chilblain lupus. Methods: The demographic data, medical history, and physical examination of the patients were obtained. Whole-exome sequencing and Sanger sequencing were performed. The Interferon-stimulated gene (ISG) score was analyzed. Results: We reported four patients with a novel UNC93B1 c.1007G>A p.R336H variant, including three presenting with Juvenile arthritis or rheumatoid arthritis, and one with a predominant disease phenotype of ITP. Besides arthritis, these patients presented with dominant interstitial pneumonia. ISGs expression analysis in the active disease state revealed over-expressed IFN-stimulated cytokine genes and elevated ISG score in P4. So far, 25 cases with UNC93B1 pathogenic mutation have been reported, including 13 presenting with childhood-onset systemic lupus erythematosus (SLE), and 12 with cutaneous lupus. Management of these patients was variable based on clinical manifestations. Conclusion: UNC93B1-mutation-associated disease should be contemplated in the context of the early-onset autoimmune disease, especially childhood-onset SLE, Juvenile arthritis, and rheumatoid arthritis. Pulmonary involvement should be monitored in this disease.