{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:06:29Z","timestamp":1758845189896,"version":"3.44.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Zeta-chain-associated protein kinase 70 (<jats:italic>ZAP70<\/jats:italic>) deficiency is a rare autosomal recessive T<jats:sup>+<\/jats:sup>B<jats:sup>+<\/jats:sup>NK<jats:sup>+<\/jats:sup> combined immunodeficiency characterized by heterogeneous clinical and immunologic phenotypes. Because of the limited number of reported cases, data guiding optimal management and hematopoietic stem cell transplantation (HSCT) strategies remain scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively reviewed all patients with genetically confirmed <jats:italic>ZAP70<\/jats:italic> deficiency treated at King Faisal Specialist Hospital and Research Centre. Data on pre-HSCT clinical and immunologic features, transplant characteristics, post-HSCT complications, immune reconstitution, and long-term outcomes were recorded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirteen patients with a median age at symptom onset of 1 month were identified. The most frequent initial presentations were recurrent respiratory infections and cutaneous manifestations. Autoimmune complications and lymphoproliferation were observed in several patients. Eleven of thirteen patients (84.6%) exhibited profound CD8<jats:sup>+<\/jats:sup> T-cell lymphopenias and two had near-normal CD8<jats:sup>+<\/jats:sup> T-cell counts with impaired T-cell function. Eleven patients underwent HSCT, including seven from Human Leukocyte Antigen (HLA)-matched family donors, two from one-antigen mismatched related donors, one from a haploidentical mother (matched for graft-versus-host disease risk but mismatched for rejection), and one from an unrelated cord blood donor. Two patients required a second transplant because of poor immune reconstitution. Of the 11 patients who underwent HSCT, 8 (73%) remain alive with a median follow-up of 7 years (range, 1\u201315), and most demonstrated resolution of clinical manifestations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HSCT remains the only curative treatment for <jats:italic>ZAP70<\/jats:italic> deficiency. Myeloablative conditioning regimens appear to promote more robust and durable immune reconstitution. In critically ill patients with severe infections or end-organ damage, reduced-intensity or unconditioned HSCT can be considered as a life-saving approach, although subsequent interventions might be necessary.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1656240","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T05:31:23Z","timestamp":1758778283000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical, immunological, molecular characteristics and outcomes of stem cell transplantation in ZAP70 deficiency: a single-center experience"],"prefix":"10.3389","volume":"16","author":[{"given":"Fai","family":"AlQahtani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azhar","family":"Al 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