Primary T-cell immunodeficiency with functional revertant somatic mosaicism in  CD247

Marín, Ana V.; Jiménez-Reinoso, Anaïs; Briones, Alejandro C.; Muñoz-Ruiz, Miguel; Aydoğmuş, Çiğdem; Pasick, Luke J.; Couso, Jorge; Mazariegos, Marina S.; Álvarez-Prado, Ángel F.; Blázquez-Moreno, Alfonso; Çipe, Funda; Haskoloğlu, Şule; Doğu, Figen; Morín, Matías; Moreno-Pelayo, Miguel A.; García‐Sánchez, Félix; Gil-Herrera, Juana; Fernández-Malavé, Edgar; Reyburn, Hugh; Ramiro, Almudena R.; İkincioğulları, Aydan; Recio, María J.; Regueiro, José R.; Garcillán, Beatriz

doi:10.1016/j.jaci.2016.06.020

Cited by 18 publications

(14 citation statements)

References 13 publications

(12 reference statements)

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“…Mutations in those chains impair T cell development to varying degrees. Deficiency of CD3δ or CD3ε causes severe T cell lymphopenia, while CD3γ or CD247 (CD3Z) causes mild T cell lymphopenia, and this probably explains the normal TREC level in our patient with CD3Z defect [42].…”

Section: Discussionmentioning

confidence: 99%

TREC and KREC profiling as a representative of thymus and bone marrow output in patients with various inborn errors of immunity

Dasouki

Jabr

Aldakheel

et al. 2020

Clinical and Experimental Immunology

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RT‐qPCR quantification analysis of TRECs and KRECs in gDNA of patients with many diverse molecularly confirmed Primary Immunodeficiency Diseases was performed. Our data suggest that in addition to classical SCID and agammaglobulinemia, the TREC/KREC assay may identify secondary targets including some patients with ZAP70 deficiency, DOCK8 deficiency, ataxia telangiectasia, Wiskott‐Aldrich and bare lymphocyte syndromes.

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Section: Discussionmentioning

confidence: 99%

TREC and KREC profiling as a representative of thymus and bone marrow output in patients with various inborn errors of immunity

Dasouki

Jabr

Aldakheel

et al. 2020

Clinical and Experimental Immunology

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“…Thus, X-linked SCID patients were also reported with evidence of somatic reversion in IL2RG in their T cells, but not B cells, NK cells or monocytes, with the reversion event likely occurring in early T-cell precursors (7,8). Similarly, reversion has been detected in T cells in patients with SCID due to mutations in CD247 (CD3z) (9)(10)(11).…”

Section: Introductionmentioning

confidence: 97%

Somatic reversion of pathogenic DOCK8 variants alters lymphocyte differentiation and function to effectively cure DOCK8 deficiency

Pillay¹,

Fusaro²,

Gray³

et al. 2021

Journal of Clinical Investigation

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“…Altogether, CD3δ, CD3ε and CD3ζ deficiencies are responsible for a severe immune deficiency and require HSCT early in life (78). However, somatic mosaicism with gene reversion or second-site mutations restoring protein expression may allow residual T cell development and more prolonged survival, leading to atypical presentations of the disease (79). Of note, haploidentical HSCT in the absence of conditioning is typically associated with poor outcome (78, 80).…”

Section: Hematopoietic Stem Cell Transplantation For Individual Primamentioning

confidence: 99%

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Diseases: Current Status and Future Perspectives

et al. 2019

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Primary immunodeficiencies (PID) are disorders that for the most part result from mutations in genes involved in immune host defense and immunoregulation. These conditions are characterized by various combinations of recurrent infections, autoimmunity, lymphoproliferation, inflammatory manifestations, atopy, and malignancy. Most PID are due to genetic defects that are intrinsic to hematopoietic cells. Therefore, replacement of mutant cells by healthy donor hematopoietic stem cells (HSC) represents a rational therapeutic approach. Full or partial ablation of the recipient's marrow with chemotherapy is often used to allow stable engraftment of donor-derived HSCs, and serotherapy may be added to the conditioning regimen to reduce the risks of graft rejection and graft versus host disease (GVHD). Initially, hematopoietic stem cell transplantation (HSCT) was attempted in patients with severe combined immunodeficiency (SCID) as the only available curative treatment. It was a challenging procedure, associated with elevated rates of morbidity and mortality. Overtime, outcome of HSCT for PID has significantly improved due to availability of high-resolution HLA typing, increased use of alternative donors and new stem cell sources, development of less toxic, reduced-intensity conditioning (RIC) regimens, and cellular engineering techniques for graft manipulation. Early identification of infants affected by SCID, prior to infectious complication, through newborn screening (NBS) programs and prompt genetic diagnosis with Next Generation Sequencing (NGS) techniques, have also ameliorated the outcome of HSCT. In addition, HSCT has been applied to treat a broader range of PID, including disorders of immune dysregulation. Yet, the broad spectrum of clinical and immunological phenotypes associated with PID makes it difficult to define a universal transplant regimen. As such, integration of knowledge between immunologists and transplant specialists is necessary for the development of innovative transplant protocols and to monitor their results during follow-up. Despite the improved outcome observed after HSCT, patients with severe forms of PID still face significant challenges of short and long-term transplant-related complications. To address this issue, novel HSCT strategies are being implemented aiming to improve both survival and long-term quality of life. This article will discuss the current status and latest developments in HSCT for PID, and present data regarding approach and outcome of HSCT in recently described PID, including disorders associated with immune dysregulation.

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Primary T-cell immunodeficiency with functional revertant somatic mosaicism in CD247

Cited by 18 publications

References 13 publications

TREC and KREC profiling as a representative of thymus and bone marrow output in patients with various inborn errors of immunity

TREC and KREC profiling as a representative of thymus and bone marrow output in patients with various inborn errors of immunity

Somatic reversion of pathogenic DOCK8 variants alters lymphocyte differentiation and function to effectively cure DOCK8 deficiency

Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Diseases: Current Status and Future Perspectives

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