Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4+/-) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. OBJECTIVE: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up. METHODS: The 98 patients (63 LRBA-/- and 35 CTLA4+/-) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies. RESULTS: The LRBA-/- patients exhibited a more severe disease course than did the CTLA4+/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA-/- patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival. CONCLUSIONS: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.

Primary hypoparathyroidism in a patient with common variable immunodeficiency associated enteropathy.

Background. Common variable immunodeficiency (CVID) is a rare disease characterized by humoral immunodeficiency, often causing sinopulmonary and gastrointestinal infections, and may cause enteropathy in some patients, which leads to severe malnutrition and electrolyte deficiencies. Although many autoimmune diseases are seen with increased frequency in CVID patients, primary hypoparathyroidism is extremely rare.Case presentation. A 50-year-old man with CVID presented with diarrhea. The patient had complaints for 2 years and was cachectic. He had severe electrolyte and vitamin deficiencies that did not respond to oral treatment. The diarrhea causes such as celiac, inflammatory bowel diseases, and gastrointestinal infections were excluded and the endoscopy showed enteropathic changes in the duodenum and colon. Concomitant hypoparathyroidism was also detected in the patient with hypocalcemia despite adequate replacement.Conclusion. Parenteral therapy should be considered in the management of CVID enteropathy cases that do not respond to oral replacement. Although very rare, hypoparathyroidism should be considered in the differential diagnosis of CVID patients with treatment-resistant hypocalcemia.