Leaky Artemis Deficiency and EBV-Related Lymphoproliferative Disease: A Novel Case and Review of the Literature.

INTRODUCTION

Artemis () deficiency causes radiosensitive severe combined immunodeficiency (SCID), although hypomorphic cases can manifest later-onset immunodeficiency, autoimmunity, or lymphoproliferation. We report a 45-year-old man with humoral immunodeficiency, opportunistic infections, and recurrent EBV-positive diffuse large B-cell lymphoma (DLBCL).

METHODS

Genetic analysis was performed to identify mutations in the gene. Functional studies, including γH2AX assays to assess DNA damage repair and measurement of Type I interferon responses, were conducted to evaluate the impact of the variant. A literature review was performed to contextualize the findings.

RESULTS

Biallelic p.Leu70del frameshift mutation in was identified, leading to significantly decreased mutant protein expression. Functional testing confirmed impaired DNA damage repair, via γH2AX measurement, and elevated Type I interferon responses, indicating cytosolic DNA damage accumulation. A literature review highlighted EBV-positive lymphomas in leaky Artemis deficiency with high mortality rate.

CONCLUSION

Our report adds hypomorphic deficiency as an inborn error of immunity that predisposes to EBV-associated lymphoproliferative disease.

TRIAL REGISTRATION

The authors have confirmed clinical trial registration is not needed for this submission.