Abstract
BACKGROUND: IL2RG and JAK3 mutations cause T-cell-negative, B-cell-positive, natural killer cell-negative severe combined immunodeficiency (SCID). Cell therapies such as hematopoietic stem cell transplantation (or gene therapy for IL2RG deficiency) can effectively restore T-cell immunity but-when performed without myeloablation-may leave residual immune defects. These include persistent B-cell dysfunction, poor innate lymphoid cell recovery, and poor reconstitution of secondary lymphoid organs. Severe/recurrent warts may also occur in the long term. OBJECTIVE: We present 3 IL2RG SCID cases complicated by lymphedema and discuss possible hypotheses of this rare complication. METHODS: We describe 3 patients with IL2RG SCID who developed lymphedema: 2 after unconditioned cell therapy and 1 with a hypomorphic mutation who remained untreated. Clinical presentation, immunologic data, imaging, and transplant history were reviewed and compared with published data. RESULTS: Lymphedema affected the lower limbs and varied in severity, with one case complicated by recurrent dermohypodermitis and Streptococcus mitis sepsis. CONCLUSION: Lymphedema is a rare but potentially disabling complication of IL2RG/JAK3 SCID, affecting long-term quality of life. Hypothetically, low/absent levels of innate lymphoid cells-particularly lymphoid tissue inducer cells, a subset of innate lymphoid cells-may be a contributing factor in the pathogenesis of lymphedema in IL2RG/JAK3 SCID.