Case report : Challenges in immune reconstitution following hematopoietic stem cell transplantation for CTLA-4 insufficiency-like primary immune regulatory disorders
Margarit-Soler, Adriana (Hospital Sant Joan de Déu (Manresa))
Deyà-Martínez, Ángela (Hospital Clínic i Provincial de Barcelona)
Canizales, Juan Torres (Hospital Clínic i Provincial de Barcelona)
Vlagea, Alexandru (Hospital Clínic i Provincial de Barcelona)
García-García, Ana (Hospital Clínic i Provincial de Barcelona)
Marsal, Júlia (Hospital Sant Joan de Déu (Manresa))
Trabazo del Castillo, María (Hospital Sant Joan de Déu (Manresa))
Planas, Sílvia (Hospital Sant Joan de Déu (Manresa))
Simó, Sílvia (Hospital Sant Joan de Déu (Manresa))
Esteve-Sole, Ana (Hospital Clínic i Provincial de Barcelona)
Suárez-Lledó Grande, María (Hospital Clínic i Provincial de Barcelona)
Badell Serra, Isabel (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Rovira Tarrats, Montserrat (Hospital Clínic i Provincial de Barcelona)
Fernandez Aviles, Francesc (Hospital Clínic i Provincial de Barcelona)
Alsina Manrique, Laia (Hospital Clínic i Provincial de Barcelona)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	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.
Grants:	Instituto de Salud Carlos III PI18/00223 Instituto de Salud Carlos III PI21/00211
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Abatacept ; Chimerism ; CTLA-4 ; Hematopoietic stem cell transplantation ; Immune reconstitution ; Primary immunodeficiency
Published in:	Frontiers in immunology, Vol. 13 (december 2022) , ISSN 1664-3224

DOI: 10.3389/fimmu.2022.1070068
PMID: 36636328

10 p, 1.0 MB

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