Outcomes of X-linked agammaglobulinaemia patients
Outcomes of X-linked agammaglobulinaemia patients
Background: X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications. Objectives: To describe the clinical outcomes of XLA patients in the United Kingdom and Hong Kong and evaluate current treatment strategies. Methods: Patients with a definitive diagnosis of XLA were included in this cross-sectional and retrospective analysis of clinical health outcomes. Data pertaining to diagnosis, infection incidence, IgG trough levels and lung function were collected and analysed. Results: 99 patients with a median age of 29.02 years (IQR 12.83–37.41) and a total follow up of 1922 patient years, were included this study. The median age at diagnosis was 3.30 years (IQR 1.04–8.38) which decreased over time (p = 0.004). 40% of the cohort had radiological evidence of bronchiectasis. Risk of bronchiectasis was not significantly associated with clinical infection incidence (p = 0.880) or IgG trough levels (p = 0.407). Two patients demonstrated novel complications, namely persistent norovirus infection, leading to haemopoietic stem cell transplantation (HSCT). Conclusions: Despite modern therapy, most XLA patients continue to experience complications, most notably bronchiectasis, likely due to absence of IgA/M in current therapies, but lack of B lymphocytes may also lead to additional sequalae. These data strongly support the need for further research, particularly that of curative modalities including HSCT and gene therapy.
Agammaglobulinemia, Antibody Deficiency, Bronchiectasis, Immunodeficiency, Immunoglobulin, XLA
Shillitoe, Ben
3ac214b8-5184-4fe2-bdd8-567b35309178
Duque, Jaime S.Rosa
de60cf38-26aa-4a38-95be-2dc9f6033162
Lai, Sophie H.Y.
8222c5e6-b8ac-4e6f-92b8-418f8358eb4c
Lau, Tsun Ming
44f083be-1259-41e8-876c-c94813023601
Chan, Jeffery C.H.
2f93cf63-7883-4cce-8e6e-ea9e06fc0726
Bourne, Helen
51e25604-6bb3-4687-ab1c-b161684f85a3
Stroud, Catherine
ed08cf6f-fae1-4e6e-a80a-a513ad4a5196
Flood, Terry
069841db-899d-40cf-b18f-0e81b16a137e
Buckland, Matthew
434c6211-6245-45c3-9b88-0444137bff72
Ip, Winnie
6fc3e1a5-8c3a-48ea-9f9f-a445f34051dd
Worth, Austen
6e9e0b1c-30f7-4b17-8fa6-46c4e17d5a74
Hackett, Scott
0c5c1e69-2d31-4a69-bc9d-bf332ae81294
Herwadkar, Archana
12cd4356-72e3-4abd-9a39-502b4b2dffee
Coulter, Tanya
da69d8ce-fd0e-4aa6-ba37-6ed402cffcfa
Blaney, Catherine
4117e02a-9b48-490e-8130-52e171fc17e6
Jolles, Stephen
524b56e6-6b76-43b5-9a4e-9aa3c0366cba
Garcez, Tomaz
92a21cf3-af2c-4fe6-bde4-931d8f731930
Moya, Eduardo
975edff7-ef6f-4de2-a6e5-b72ad321a02b
Faust, Saul
f97df780-9f9b-418e-b349-7adf63e150c1
Pearce, Mark S.
b50b01fe-e8a4-4484-8539-3bdeba5d79d9
Lau, Yu Lung
f5f69715-1058-4a6c-b586-6ce89801d36c
Gennery, Andrew R.
170e9fd1-c65e-4beb-b39f-345d288b3ca8
Shillitoe, Ben
3ac214b8-5184-4fe2-bdd8-567b35309178
Duque, Jaime S.Rosa
de60cf38-26aa-4a38-95be-2dc9f6033162
Lai, Sophie H.Y.
8222c5e6-b8ac-4e6f-92b8-418f8358eb4c
Lau, Tsun Ming
44f083be-1259-41e8-876c-c94813023601
Chan, Jeffery C.H.
2f93cf63-7883-4cce-8e6e-ea9e06fc0726
Bourne, Helen
51e25604-6bb3-4687-ab1c-b161684f85a3
Stroud, Catherine
ed08cf6f-fae1-4e6e-a80a-a513ad4a5196
Flood, Terry
069841db-899d-40cf-b18f-0e81b16a137e
Buckland, Matthew
434c6211-6245-45c3-9b88-0444137bff72
Ip, Winnie
6fc3e1a5-8c3a-48ea-9f9f-a445f34051dd
Worth, Austen
6e9e0b1c-30f7-4b17-8fa6-46c4e17d5a74
Hackett, Scott
0c5c1e69-2d31-4a69-bc9d-bf332ae81294
Herwadkar, Archana
12cd4356-72e3-4abd-9a39-502b4b2dffee
Coulter, Tanya
da69d8ce-fd0e-4aa6-ba37-6ed402cffcfa
Blaney, Catherine
4117e02a-9b48-490e-8130-52e171fc17e6
Jolles, Stephen
524b56e6-6b76-43b5-9a4e-9aa3c0366cba
Garcez, Tomaz
92a21cf3-af2c-4fe6-bde4-931d8f731930
Moya, Eduardo
975edff7-ef6f-4de2-a6e5-b72ad321a02b
Faust, Saul
f97df780-9f9b-418e-b349-7adf63e150c1
Pearce, Mark S.
b50b01fe-e8a4-4484-8539-3bdeba5d79d9
Lau, Yu Lung
f5f69715-1058-4a6c-b586-6ce89801d36c
Gennery, Andrew R.
170e9fd1-c65e-4beb-b39f-345d288b3ca8
Shillitoe, Ben, Duque, Jaime S.Rosa, Lai, Sophie H.Y., Lau, Tsun Ming, Chan, Jeffery C.H., Bourne, Helen, Stroud, Catherine, Flood, Terry, Buckland, Matthew, Ip, Winnie, Worth, Austen, Hackett, Scott, Herwadkar, Archana, Coulter, Tanya, Blaney, Catherine, Jolles, Stephen, Garcez, Tomaz, Moya, Eduardo, Faust, Saul, Pearce, Mark S., Lau, Yu Lung and Gennery, Andrew R.
(2024)
Outcomes of X-linked agammaglobulinaemia patients.
Journal of Clinical Immunology, 45 (1), [40].
(doi:10.1007/s10875-024-01829-z).
Abstract
Background: X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications. Objectives: To describe the clinical outcomes of XLA patients in the United Kingdom and Hong Kong and evaluate current treatment strategies. Methods: Patients with a definitive diagnosis of XLA were included in this cross-sectional and retrospective analysis of clinical health outcomes. Data pertaining to diagnosis, infection incidence, IgG trough levels and lung function were collected and analysed. Results: 99 patients with a median age of 29.02 years (IQR 12.83–37.41) and a total follow up of 1922 patient years, were included this study. The median age at diagnosis was 3.30 years (IQR 1.04–8.38) which decreased over time (p = 0.004). 40% of the cohort had radiological evidence of bronchiectasis. Risk of bronchiectasis was not significantly associated with clinical infection incidence (p = 0.880) or IgG trough levels (p = 0.407). Two patients demonstrated novel complications, namely persistent norovirus infection, leading to haemopoietic stem cell transplantation (HSCT). Conclusions: Despite modern therapy, most XLA patients continue to experience complications, most notably bronchiectasis, likely due to absence of IgA/M in current therapies, but lack of B lymphocytes may also lead to additional sequalae. These data strongly support the need for further research, particularly that of curative modalities including HSCT and gene therapy.
Text
XLA Outcomes in the UK and HK_JoCI_revised
- Accepted Manuscript
Restricted to Repository staff only until 14 December 2025.
Request a copy
More information
Accepted/In Press date: 28 October 2024
e-pub ahead of print date: 14 November 2024
Additional Information:
Publisher Copyright:
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
Keywords:
Agammaglobulinemia, Antibody Deficiency, Bronchiectasis, Immunodeficiency, Immunoglobulin, XLA
Identifiers
Local EPrints ID: 496350
URI: http://eprints.soton.ac.uk/id/eprint/496350
ISSN: 0271-9142
PURE UUID: 07889222-0fc1-492a-a389-92b9516cfafb
Catalogue record
Date deposited: 12 Dec 2024 17:39
Last modified: 13 Dec 2024 02:41
Export record
Altmetrics
Contributors
Author:
Ben Shillitoe
Author:
Jaime S.Rosa Duque
Author:
Sophie H.Y. Lai
Author:
Tsun Ming Lau
Author:
Jeffery C.H. Chan
Author:
Helen Bourne
Author:
Catherine Stroud
Author:
Terry Flood
Author:
Matthew Buckland
Author:
Winnie Ip
Author:
Austen Worth
Author:
Scott Hackett
Author:
Archana Herwadkar
Author:
Tanya Coulter
Author:
Catherine Blaney
Author:
Stephen Jolles
Author:
Tomaz Garcez
Author:
Eduardo Moya
Author:
Mark S. Pearce
Author:
Yu Lung Lau
Author:
Andrew R. Gennery
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
