{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:17:28Z","timestamp":1790756248974,"version":"4.1.0"},"reference-count":14,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunopathol Pharmacol"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>\n                    Autoimmune lymphoproliferative syndrome (ALPS) usually presents in childhood with fever, nonmalignant splenomegaly, and lymphadenopathy along with cytopenia, which is caused by mutations in the FAS apoptotic pathway. The TCR\u03b1\u03b2\u2009+\u2009CD4\/CD8 double-negative T cells (DNT), one of required criteria of ALPS, will rise markedly in ALPS. Human Protein kinase C delta (PRKCD) deficiency (OMIM # 615559) was recently identified to be causative for an ALPS-type III with significant B-cell proliferation particularly of immature B cells. We report a pedigree homozygous variation of PRKCD gene (c.36T&gt;G, p. Y12X) which presented with refractory cytopenia, splenomegaly, and polarization of DNT\/regulatory T cells (Treg) axis. After repeated recurrence, the patient was treated with mTOR inhibitor sirolimus, which had a safety mechanism and specifically rebalance the DNT\/Treg axis. The patient\u2019s hemoglobin and clinical condition improved gradually by the application of sirolimus (1.5\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    , actual blood concentration 4.27\u201310.3\u2009ng\/l). Homozygous variation in PRKCD may lead to typical ALPS clinical manifestations. Targeting DNT\/Treg axis, use of sirolimus in such patients may help to achieve good clinical control.\n                  <\/jats:p>","DOI":"10.1177\/20587384211025934","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T02:15:12Z","timestamp":1625019312000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Sirolimus is effective in autoimmune lymphoproliferative syndrome-type III: A pedigree case report with homozygous variation PRKCD"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4278-8559","authenticated-orcid":false,"given":"Hao","family":"Gu","sequence":"first","affiliation":[{"name":"Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, No. 56 Nanlishi Road, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenping","family":"Chen","sequence":"additional","affiliation":[{"name":"Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, No. 56 Nanlishi Road, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, No. 56 Nanlishi Road, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhui","family":"Wu","sequence":"additional","affiliation":[{"name":"Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, No. 56 Nanlishi Road, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyou","family":"Wang","sequence":"additional","affiliation":[{"name":"Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, National Center for Children\u2019s Health, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"issue":"3","key":"bibr1-20587384211025934","first-page":"233","volume":"9","author":"Teachey DT","year":"2011","journal-title":"Clinical Advances in Hematology & 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