Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency

Abstract Background Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity and lymphoproliferation. The long-term efficacy of CTLA4-Ig (abatacept) as targeted therapy for its immune dysregulatory features remains to be established. Objective We sought to determine the clinical and immunological features of LRBA-deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations. Methods Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunological responses. LRBA expression, lymphocyte subpopulations and circulating T follicular helper (cT FH ) cells were determined by flow cytometry. Results The mean age of the patients was 13.4±7.9 years and the follow up period was 3.4±2.3 years. Recurrent infections (n:19, 86.4%), immune dysregulation (ID, n:18, 81.8%) and lymphoproliferation (LP, n:16, 72.7%) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of LP and chronic diarrhea (CD) followed by ID, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared to every 4-weeks. There were no serious side effects related to the abatacept therapy. cT FH cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in the majority of subjects. However, high cT FH cell frequencies persisted in two patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy. Conclusion Long-term Abatacept therapy is effective in the majority of patients with LRBA deficiency.