Hemophagocytic lymphohistiocytosis in a patient with CD3δ deficiency
Abstract
Introduction: Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory process that has been linked to abnormal cytotoxic T-cell and natural killer (NK) cell function. We report on the first case of severe combined immunodeficiency (SCID) caused by a CD3δ mutation presenting with HLH in a female of Mennonite descent.
Case Description: A Low-German-speaking Mennonite female with past medical history of eczema, mouth sores, and refractory oral and diaper candidiasis presented at the age of 6 months with vomiting, diarrhea, and lethargy. The patient developed HLH that was refractory to treatment and led to multi-organ failure. Immunological evaluation was diagnostic for SCID and post-mortem genetic testing confirmed a homozygous mutation in CD3δ that was previously described in Mennonites.
Method: Targeted molecular testing for CD3δ deficiency confirmed a homozygous C-to-T transition at nucleotide position 202, predicting a premature stop codon, with a truncation at residue 68 (R68X) in the extracellular domain of the protein.
Discussion: Many primary immunodeficiency diseases (PID) that affect cytotoxic T cells and NK cells have presented with HLH. However, a growing number of PID with no obvious NK-cell defect have also been found to predispose patients to HLH, suggesting that failure of NK activity is not the only mechanism leading to this unusual form of inflammation.
Conclusion: CD3δ is known to be critical for T-cell but not NK-cell development, which may suggest an alternate mechanism for overwhelming inflammation leading to HLH.
Statement of novelty: This is the first case report of CD3δ deficiency presenting with HLH.
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Published In
LymphoSign Journal
Volume 2 • Number 4 • December 2015
Pages: 201 - 206
History
Received: 22 April 2015
Accepted: 26 August 2015
Accepted manuscript online: 27 August 2015
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Mohammad Alsalamah, Amrita Sarpal, Victoria Mok Siu, Paul Gibson, CA Rupar, Michelle Barton, Marina I Salvadori, and Sharan Goobie. 2015. Hemophagocytic lymphohistiocytosis in a patient with CD3δ deficiency. LymphoSign Journal.
2(4): 201-206. https://doi.org/10.14785/lpsn-2015-0006
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