PMID- 36636328 OWN - NLM STAT- MEDLINE DCOM- 20230116 LR - 20230118 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Case report: Challenges in immune reconstitution following hematopoietic stem cell transplantation for CTLA-4 insufficiency-like primary immune regulatory disorders. PG - 1070068 LID - 10.3389/fimmu.2022.1070068 [doi] LID - 1070068 AB - Cytotoxic T-lymphocyte antigen-4 (CTLA-4) haploinsufficiency is a T-cell hyperactivation disorder that can manifest with both immunodeficiency and immune dysregulation. Approximately one-third of patients may present mild symptoms and remain stable under supportive care. The remaining patients may develop severe multiorgan autoimmunity requiring lifelong immunosuppressive treatment. Hematopoietic stem cell transplantation (HSCT) is potentially curable for patients with treatment-resistant immune dysregulation. Nevertheless, little experience is reported regarding the management of complications post-HSCT. We present case 1 (CTLA-4 haploinsufficiency) and case 2 (CTLA-4 insufficiency-like phenotype) manifesting with severe autoimmunity including cytopenia and involvement of the central nervous system (CNS), lung, and gut and variable impairment of humoral responses. Both patients underwent HSCT for which the main complications were persistent mixed chimerism, infections, and immune-mediated complications [graft-versus-host disease (GVHD) and nodular lung disease]. Detailed management and outcomes of therapeutic interventions post-HSCT are discussed. Concretely, post-HSCT abatacept and human leukocyte antigen (HLA)-matched sibling donor lymphocyte infusions may be used to increase T-cell donor chimerism with the aim of correcting the immune phenotype of CTLA-4 haploinsufficiency. CI - Copyright (c) 2022 Margarit-Soler, Deya-Martinez, Canizales, Vlagea, Garcia-Garcia, Marsal, Del Castillo, Planas, Simo, Esteve-Sole, Grande, Badell, Tarrats, Fernandez-Aviles and Alsina. FAU - Margarit-Soler, Adriana AU - Margarit-Soler A AD - Bone Marrow Transplant Unit, Oncology Service, Hospital Sant Joan de Deu, Barcelona, Spain. FAU - Deya-Martinez, Angela AU - Deya-Martinez A AD - Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Deu, Barcelona, Spain. AD - Study Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Deu, Barcelona, Spain. AD - Clinical Immunology Program Hospital Sant Joan de Deu-Hospital Clinic Barcelona, Barcelona, Spain. FAU - Canizales, Juan Torres AU - Canizales JT AD - Clinical Immunology Unit, Department of Immunology, Biomedical Diagnostic Center, Hospital Clinic of Barcelona-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. FAU - Vlagea, Alexandru AU - Vlagea A AD - Clinical Immunology Unit, Department of Immunology, Biomedical Diagnostic Center, Hospital Clinic of Barcelona-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. FAU - Garcia-Garcia, Ana AU - Garcia-Garcia A AD - Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Deu, Barcelona, Spain. AD - Study Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Deu, Barcelona, Spain. AD - Clinical Immunology Program Hospital Sant Joan de Deu-Hospital Clinic Barcelona, Barcelona, Spain. FAU - Marsal, Julia AU - Marsal J AD - Bone Marrow Transplant Unit, Oncology Service, Hospital Sant Joan de Deu, Barcelona, Spain. FAU - Del Castillo, Maria Trabazo AU - Del Castillo MT AD - Bone Marrow Transplant Unit, Oncology Service, Hospital Sant Joan de Deu, Barcelona, Spain. FAU - Planas, Silvia AU - Planas S AD - Department of Pathology, Hospital Sant Joan de Deu, Barcelona, Spain. FAU - Simo, Silvia AU - Simo S AD - Infectious Diseases Unit, Department of Pediatrics, Hospital Sant Joan de Deu, Barcelona, Spain. AD - Center for Biomedical Network Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain. FAU - Esteve-Sole, Ana AU - Esteve-Sole A AD - Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Deu, Barcelona, Spain. AD - Study Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Deu, Barcelona, Spain. AD - Clinical Immunology Program Hospital Sant Joan de Deu-Hospital Clinic Barcelona, Barcelona, Spain. FAU - Grande, Maria Suarez-Lledo AU - Grande MS AD - Hematopoietic Transplantation Unit, Hematology Department, Clinical Institute of Hematology and Oncology (ICMHO), Hospital Clinic de Barcelona, Barcelona, Spain. AD - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain. AD - Department of Surgery and Surgical Specializations, Facultat de Medicina i Ciencies de la Salut, Universitat de Barcelona, Barcelona, Spain. FAU - Badell, Isabel AU - Badell I AD - Bone Marrow Transplant Unit, Oncology Service, Hospital Sant Joan de Deu, Barcelona, Spain. AD - Pediatric Haematology and Stem Cell Transplantation Unit, Pediatric Department, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Tarrats, Montserrat Rovira AU - Tarrats MR AD - Bone Marrow Transplant Unit, Oncology Service, Hospital Sant Joan de Deu, Barcelona, Spain. AD - Hematopoietic Transplantation Unit, Hematology Department, Clinical Institute of Hematology and Oncology (ICMHO), Hospital Clinic de Barcelona, Barcelona, Spain. AD - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain. FAU - Fernandez-Aviles, Francesc AU - Fernandez-Aviles F AD - Hematopoietic Transplantation Unit, Hematology Department, Clinical Institute of Hematology and Oncology (ICMHO), Hospital Clinic de Barcelona, Barcelona, Spain. AD - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain. FAU - Alsina, Laia AU - Alsina L AD - Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Deu, Barcelona, Spain. AD - Study Group for Immune Dysfunction Diseases in Children (GEMDIP), Institut de Recerca Sant Joan de Deu, Barcelona, Spain. AD - Clinical Immunology Program Hospital Sant Joan de Deu-Hospital Clinic Barcelona, Barcelona, Spain. AD - Department of Surgery and Surgical Specializations, Facultat de Medicina i Ciencies de la Salut, Universitat de Barcelona, Barcelona, Spain. LA - eng PT - Case Reports PT - Research Support, Non-U.S. Gov't DEP - 20221227 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (CTLA-4 Antigen) SB - IM MH - Humans MH - CTLA-4 Antigen/genetics MH - *Immune Reconstitution MH - T-Lymphocytes MH - *Graft vs Host Disease/etiology MH - *Hematopoietic Stem Cell Transplantation/adverse effects PMC - PMC9831655 OTO - NOTNLM OT - CTLA-4 OT - abatacept OT - chimerism OT - hematopoietic stem cell transplantation OT - immune reconstitution OT - primary immunodeficiency COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/01/14 06:00 MHDA- 2023/01/17 06:00 PMCR- 2022/01/01 CRDT- 2023/01/13 02:00 PHST- 2022/10/14 00:00 [received] PHST- 2022/11/28 00:00 [accepted] PHST- 2023/01/13 02:00 [entrez] PHST- 2023/01/14 06:00 [pubmed] PHST- 2023/01/17 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.1070068 [doi] PST - epublish SO - Front Immunol. 2022 Dec 27;13:1070068. doi: 10.3389/fimmu.2022.1070068. eCollection 2022.