Adult-Onset LRBA Deficiency Presenting with Rheumatoid Arthritis-Like Manifestations: A Case Report.

Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency is a primary inborn error of immunity characterized by immune dysregulation and frequently associated with autoimmune connective tissue manifestations. We describe an adult woman diagnosed with rheumatoid arthritis who was subsequently found to have LRBA deficiency based on genetic testing and investigated inflammatory proteins potentially involved in the pathogenesis of LRBA deficiency. A 44-year-old woman with rheumatoid arthritis presented with persistent diarrhea and abdominal distention lasting over eight months. Abdominal imaging revealed intestinal pseudo-obstruction. Her medical history included megaloblastic anemia, type 1 diabetes, and chronic thyroiditis since childhood. Her brother had died of unexplained diarrhea during childhood. Given her multiple autoimmune manifestations and family history, a primary immune deficiency (PID) was suspected. Genetic analysis identified a heterozygous LRBA splice-site variant (c.1162-1G > A) and a possible heterozygous deletion involving exons 18-41, suggesting compound heterozygous LRBA variants. Thus, the diagnosis of LRBA deficiency-associated autoimmunity. Following the diagnosis, she was treated with abatacept, a CTLA4-immunoglobulin fusion protein, resulting in improvement of gastrointestinal symptoms. Proximity extension assay (Olink