Lymphedema in patients with X-linked severe combined immunodeficiency

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.

We present 3 IL2RG SCID cases complicated by lymphedema and discuss possible hypotheses of this rare complication.

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.

Lymphedema affected the lower limbs and varied in severity, with one case complicated by recurrent dermohypodermitis and Streptococcus mitis sepsis.

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.