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Intact B-Cell Signaling and Function With Host B-Cells 47 Years After Transplantation for X-SCID
Introduction: Severe Combined Immunodeficiency (SCID) is a life-threatening immunodeficiency caused by several pathogenic genetic variants, and it is characterized by profound defects in T-cell numbers and immune function. First performed in the late 1960's, hematopoietic stem cell transplantat...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099040/ https://www.ncbi.nlm.nih.gov/pubmed/32265911 http://dx.doi.org/10.3389/fimmu.2020.00415 |
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author | Deal, Christin Thauland, Timothy J. Stiehm, E. Richard Garcia-Lloret, Maria I. Butte, Manish J. |
author_facet | Deal, Christin Thauland, Timothy J. Stiehm, E. Richard Garcia-Lloret, Maria I. Butte, Manish J. |
author_sort | Deal, Christin |
collection | PubMed |
description | Introduction: Severe Combined Immunodeficiency (SCID) is a life-threatening immunodeficiency caused by several pathogenic genetic variants, and it is characterized by profound defects in T-cell numbers and immune function. First performed in the late 1960's, hematopoietic stem cell transplantation remains the standard treatment for most cases of SCID. There is a growing number of post-transplant SCID patients, and it is imperative to assess the long-term outcomes of these patients. We have reported here the longest follow-up of a post-transplant SCID patient who, to our knowledge, bears the first gamma chain (γc) variant to show intact IL-21 signaling. Case Presentation: The patient presented at 5 months of age with recurrent thrush and Pneumocystis jiroveci pneumonia. In 1971, at the age of 11 months, he received an unconditioned, matched, related donor transplant comprising whole, unprocessed bone marrow. He is now 48 years old without significant illness and has never required immunoglobulin replacement. He exhibits T-dependent vaccine responses. He does suffer from chronic warts and bacterial infections that have worsened in recent years. We confirmed a known pathogenic variant in the IL2RG gene showing a hemizygous variant NM_000206.2:c.675C>A, resulting in p.Ser225Arg. His chimerism studies revealed donor T cells, host B cells, host myeloid cells, and mixed NK cells. Lymphocyte enumeration revealed normal numbers and distribution of B cells. The host B cells carry the pathogenic variant in IL2RG, but, when stimulated with IL-21, they demonstrated intact, γc-dependent signaling. Conclusions: Even with host B cells, reconstitution with donor T cells can be sufficient to allow over four decades of survival when B-cell function is intact. Our case demonstrates that satisfactory B-cell function can arise as a consequence of both intact IL-21 signaling due to a hypomorphic γc variant, and close HLA matching with the donor to allow for effective T-cell help. |
format | Online Article Text |
id | pubmed-7099040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70990402020-04-07 Intact B-Cell Signaling and Function With Host B-Cells 47 Years After Transplantation for X-SCID Deal, Christin Thauland, Timothy J. Stiehm, E. Richard Garcia-Lloret, Maria I. Butte, Manish J. Front Immunol Immunology Introduction: Severe Combined Immunodeficiency (SCID) is a life-threatening immunodeficiency caused by several pathogenic genetic variants, and it is characterized by profound defects in T-cell numbers and immune function. First performed in the late 1960's, hematopoietic stem cell transplantation remains the standard treatment for most cases of SCID. There is a growing number of post-transplant SCID patients, and it is imperative to assess the long-term outcomes of these patients. We have reported here the longest follow-up of a post-transplant SCID patient who, to our knowledge, bears the first gamma chain (γc) variant to show intact IL-21 signaling. Case Presentation: The patient presented at 5 months of age with recurrent thrush and Pneumocystis jiroveci pneumonia. In 1971, at the age of 11 months, he received an unconditioned, matched, related donor transplant comprising whole, unprocessed bone marrow. He is now 48 years old without significant illness and has never required immunoglobulin replacement. He exhibits T-dependent vaccine responses. He does suffer from chronic warts and bacterial infections that have worsened in recent years. We confirmed a known pathogenic variant in the IL2RG gene showing a hemizygous variant NM_000206.2:c.675C>A, resulting in p.Ser225Arg. His chimerism studies revealed donor T cells, host B cells, host myeloid cells, and mixed NK cells. Lymphocyte enumeration revealed normal numbers and distribution of B cells. The host B cells carry the pathogenic variant in IL2RG, but, when stimulated with IL-21, they demonstrated intact, γc-dependent signaling. Conclusions: Even with host B cells, reconstitution with donor T cells can be sufficient to allow over four decades of survival when B-cell function is intact. Our case demonstrates that satisfactory B-cell function can arise as a consequence of both intact IL-21 signaling due to a hypomorphic γc variant, and close HLA matching with the donor to allow for effective T-cell help. Frontiers Media S.A. 2020-03-20 /pmc/articles/PMC7099040/ /pubmed/32265911 http://dx.doi.org/10.3389/fimmu.2020.00415 Text en Copyright © 2020 Deal, Thauland, Stiehm, Garcia-Lloret and Butte. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Deal, Christin Thauland, Timothy J. Stiehm, E. Richard Garcia-Lloret, Maria I. Butte, Manish J. Intact B-Cell Signaling and Function With Host B-Cells 47 Years After Transplantation for X-SCID |
title | Intact B-Cell Signaling and Function With Host B-Cells 47 Years After Transplantation for X-SCID |
title_full | Intact B-Cell Signaling and Function With Host B-Cells 47 Years After Transplantation for X-SCID |
title_fullStr | Intact B-Cell Signaling and Function With Host B-Cells 47 Years After Transplantation for X-SCID |
title_full_unstemmed | Intact B-Cell Signaling and Function With Host B-Cells 47 Years After Transplantation for X-SCID |
title_short | Intact B-Cell Signaling and Function With Host B-Cells 47 Years After Transplantation for X-SCID |
title_sort | intact b-cell signaling and function with host b-cells 47 years after transplantation for x-scid |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099040/ https://www.ncbi.nlm.nih.gov/pubmed/32265911 http://dx.doi.org/10.3389/fimmu.2020.00415 |
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