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Immunological reconstitution in a patient with ZAP-70 deficiency following transfusion of blood lymphocytes from a previously transplanted sibling without conditioning

Bone Marrow Transplantation volume 47, pages 305–307 (2012)Cite this article

SCID is a clinically defined group of monogenetic diseases characterized by life-threatening infections in early infancy. One variant of SCID is due to defects in the Zeta-chain-associated protein (ZAP-70; MIM+176947), which results in deficient signal transduction from the TCR to the nucleus and abnormal maturation and function of thymocytes. A characteristic finding is a complete lack of circulating CD8+ T cells, whereas CD4+ T cells are present, but without function.1 Although ZAP-70 is not expressed in B cells, humoral immunity is indirectly affected because of inadequate T-cell help. Currently, hematopoietic cell transplantation represents the only curative treatment.1

We diagnosed ZAP-70 deficiency in two brothers born to consanguineous parents of Turkish origin. The family history was positive for early infant deaths in two female cousins. The older brother (sibling 1) presented at the age of 5 months with severe life-threatening pneumonia caused by Pneumocystis jirovecii, requiring mechanical ventilation for 3 weeks. In addition he developed cholestatic liver disease. No infectious agent was isolated and a biopsy revealed evidence of toxic cholangitic hepatitis with portal fibrosis. Lymphocyte phenotyping and proliferation assays showed typical findings of ZAP-70 deficiency. A homozygous missense mutation (c.C1153T) was detected in Exon 10 of the ZAP70 gene leading to a change of the amino-acid sequence from arginine to cysteine at position 385 on protein level (p.Arg385Cys), a mutation in the kinase domain of ZAP-70 not yet described. The parents and the healthy sister were found to be heterozygous carriers of this mutation.

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Author notes

  1. M Hönig and C Schuetz: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Pediatrics, University Hospital Ulm, Ulm, Germany

    M Hönig, C Schuetz, E Jacobsen, G Lahr, K-M Debatin, A Schulz & W Friedrich

  2. Institute for Clinical Transfusion Medicine and Immunogenetics Ulm and Institute of Transfusion Medicine, University Hospital Ulm, Ulm, Germany

    K Schwarz & M Rojewski

Authors
  1. M Hönig
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  2. C Schuetz
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  3. K Schwarz
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  4. M Rojewski
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  5. E Jacobsen
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  6. G Lahr
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  7. K-M Debatin
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  8. A Schulz
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  9. W Friedrich
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Correspondence to M Hönig.

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Hönig, M., Schuetz, C., Schwarz, K. et al. Immunological reconstitution in a patient with ZAP-70 deficiency following transfusion of blood lymphocytes from a previously transplanted sibling without conditioning. Bone Marrow Transplant 47, 305–307 (2012). https://doi.org/10.1038/bmt.2011.71

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