Conflict of interest: MLM developed thymus transplantation intellectual property, which has been licensed to Enzyvant Therapeutics. Both MLM and Duke University may benefit financially if the technology is commercially successful in the future.

Children with complete DiGeorge anomaly (cDGA) have congenital athymia, resulting in severe T cell immunodeficiency and susceptibility to a broad range of infections. We report the clinical course, immunologic phenotypes, treatment, and outcomes of three cases of disseminated nontuberculous mycobacterial infections (NTM) in patients with cDGA who underwent cultured thymus tissue implantation (CTTI). Two patients were diagnosed with Mycobacterium avium complex (MAC) and one patient with Mycobacterium kansasii. All three patients required protracted therapy with multiple antimycobacterial agents. One patient, who was treated with steroids due to concern for immune reconstitution inflammatory syndrome (IRIS), died due to MAC infection. Two patients have completed therapy and are alive and well. T cell counts and cultured thymus tissue biopsies demonstrated good thymic function and thymopoiesis despite NTM infection. Based on our experience with these three patients, we recommend that providers strongly consider macrolide prophylaxis upon diagnosis of cDGA. We obtain mycobacterial blood cultures when cDGA patients have fevers without a localizing source. In cDGA patients with disseminated NTM, treatment should consist of at least two antimycobacterial medications and be provided in close consultation with an infectious diseases subspecialist. Therapy should be continued until T cell reconstitution is achieved.

Immune dysregulation and autoimmuity are well-known complications of 22q11.2 deletion syndrome (22q11.2DS). GLILD has classically been assoicated with common variable immune deficiency (CVID) and has not generally been reported in other immunodeficiencies. METHODS: We describe the clinicopathological and radiological features of GLILD based on positron emission tomography (PET), computed tomography (CT), and lung biopsy in an adolescent male with 22q11.2DS and CID. RESULTS: The patient had 22q11.2DS and CID as defined by low naive T-cell numbers, decreased lymphoproliferative responses to mitogens and antigens, hypogammaglobulinemia, and suboptimal vaccine responses. He received monthly intravenous immunoglobulin and inhaled pentamidine. Routine cardiac imaging incidentally discovered bulky mediastinal lymphadenopathy, splenomegaly, and pulmonary nodules as confirmed by PET and CT. Scattered groundglass nodular opacities and central bronchiectasis were also seen. Lung biopsy histopathology and immunophenotyping showed patchy unencapsulated lymphohistiocytic nodules containing poorly formed non-necrotizing granulomata with a predominance of T-cells and follicular bronchiolitis. Following exclusion of infectious and neoplastic processes, the patient received rituximab with marked improvement. His GLILD progressed 5 months later, incidentally with repopulation of B-cells. He was retreated with rituximab followed by mercaptopurine with good response. CONCLUSIONS: We believe this is only the second reported case of GLILD in a patient with 22q11.2DS. GLILD may not be unique to CVID and should be considered as a potential cause of interstitial lung disease in other immunodeficiencies. GLILD is associated with poorer outcomes in CVID. Recognition of GLILD as a rare phenotype of 22q11.2DS and other immunodeficiencies may therefore have important therapeutic and prognostic implications.