14 years after discovery: clinical follow-up on 15 patients with inducible co-stimulator deficiencyCitation formats

  • External authors:
  • Johanna Schepp
  • Janet Chou
  • Andrea Skrabl-Baumgartner
  • Karin R. Engelhardt
  • Sophie Hambleton
  • Tomohiro Morio
  • Ekkehard Röther
  • Klaus Warnatz
  • Raif S. Geha

Standard

14 years after discovery: clinical follow-up on 15 patients with inducible co-stimulator deficiency. / Schepp, Johanna; Chou, Janet; Skrabl-Baumgartner, Andrea; Arkwright, Peter D; Engelhardt, Karin R.; Hambleton, Sophie; Morio, Tomohiro; Röther, Ekkehard; Warnatz, Klaus; Geha, Raif S.

In: Frontiers in Immunology, Vol. 8, No. 964, 16.08.2017, p. 964.

Research output: Contribution to journalArticle

Harvard

Schepp, J, Chou, J, Skrabl-Baumgartner, A, Arkwright, PD, Engelhardt, KR, Hambleton, S, Morio, T, Röther, E, Warnatz, K & Geha, RS 2017, '14 years after discovery: clinical follow-up on 15 patients with inducible co-stimulator deficiency', Frontiers in Immunology, vol. 8, no. 964, pp. 964. https://doi.org/10.3389/fimmu.2017.00964

APA

Schepp, J., Chou, J., Skrabl-Baumgartner, A., Arkwright, P. D., Engelhardt, K. R., Hambleton, S., ... Geha, R. S. (2017). 14 years after discovery: clinical follow-up on 15 patients with inducible co-stimulator deficiency. Frontiers in Immunology, 8(964), 964. https://doi.org/10.3389/fimmu.2017.00964

Vancouver

Schepp J, Chou J, Skrabl-Baumgartner A, Arkwright PD, Engelhardt KR, Hambleton S et al. 14 years after discovery: clinical follow-up on 15 patients with inducible co-stimulator deficiency. Frontiers in Immunology. 2017 Aug 16;8(964):964. https://doi.org/10.3389/fimmu.2017.00964

Author

Schepp, Johanna ; Chou, Janet ; Skrabl-Baumgartner, Andrea ; Arkwright, Peter D ; Engelhardt, Karin R. ; Hambleton, Sophie ; Morio, Tomohiro ; Röther, Ekkehard ; Warnatz, Klaus ; Geha, Raif S. / 14 years after discovery: clinical follow-up on 15 patients with inducible co-stimulator deficiency. In: Frontiers in Immunology. 2017 ; Vol. 8, No. 964. pp. 964.

Bibtex

@article{20abe576fc3e41beaaf50234828722bf,
title = "14 years after discovery: clinical follow-up on 15 patients with inducible co-stimulator deficiency",
abstract = "Background: Inducible co-stimulator (ICOS) deficiency was the first monogenic defect reported to cause common variable immunodeficiency (CVID)-like disease in 2003. Since then, 16 patients have been reported worldwide with an increasing range of clinical phenotypes.Objective: We sought to compare the clinical and immunological phenotype and provide clinical follow-up and therapeutic approaches for treating ICOS-deficient patients.Methods: We describe the clinical and laboratory data of 15 patients with available clinical data. Previous publications and clinical assessment were used as data sources.Results: The observed ICOS gene mutations were all deletions leading to undetectable protein expression. The clinical phenotype of ICOS deficiency is much broader than initially anticipated and includes not only CVID-like disease but an increased susceptibility to viral and opportunistic infections, as well as cancer. Impaired B-cell development led to decreased memory B-cells in all patients, and hypogammaglobulinemia in all but one patient. Circulating CXCR5+ CD4+ follicular T-helper-cell numbers were also reduced in all patients. Treatment included immunoglobulin replacement, regular antibiotic prophylaxis, corticosteroids, and steroid-sparing agents. Three patients underwent hematopoietic stem cell transplantation; one of them died due to capillary leak syndrome on day 5 posttransplantation.Conclusion: The disease spectrum of ICOS deficiency is expanding from solely B-cell to combined B- and T-cell immunodeficiency, suggesting genetic and environmental modifiers. Genetic diagnosis is the only tool to distinguish ICOS deficiency from other immunological defects. Patients with antibody deficiency, autoimmunity, and combined immunodeficiency should be screened for ICOS mutations.",
author = "Johanna Schepp and Janet Chou and Andrea Skrabl-Baumgartner and Arkwright, {Peter D} and Engelhardt, {Karin R.} and Sophie Hambleton and Tomohiro Morio and Ekkehard R{\"o}ther and Klaus Warnatz and Geha, {Raif S.}",
year = "2017",
month = "8",
day = "16",
doi = "10.3389/fimmu.2017.00964",
language = "English",
volume = "8",
pages = "964",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "964",

}

RIS

TY - JOUR

T1 - 14 years after discovery: clinical follow-up on 15 patients with inducible co-stimulator deficiency

AU - Schepp, Johanna

AU - Chou, Janet

AU - Skrabl-Baumgartner, Andrea

AU - Arkwright, Peter D

AU - Engelhardt, Karin R.

AU - Hambleton, Sophie

AU - Morio, Tomohiro

AU - Röther, Ekkehard

AU - Warnatz, Klaus

AU - Geha, Raif S.

PY - 2017/8/16

Y1 - 2017/8/16

N2 - Background: Inducible co-stimulator (ICOS) deficiency was the first monogenic defect reported to cause common variable immunodeficiency (CVID)-like disease in 2003. Since then, 16 patients have been reported worldwide with an increasing range of clinical phenotypes.Objective: We sought to compare the clinical and immunological phenotype and provide clinical follow-up and therapeutic approaches for treating ICOS-deficient patients.Methods: We describe the clinical and laboratory data of 15 patients with available clinical data. Previous publications and clinical assessment were used as data sources.Results: The observed ICOS gene mutations were all deletions leading to undetectable protein expression. The clinical phenotype of ICOS deficiency is much broader than initially anticipated and includes not only CVID-like disease but an increased susceptibility to viral and opportunistic infections, as well as cancer. Impaired B-cell development led to decreased memory B-cells in all patients, and hypogammaglobulinemia in all but one patient. Circulating CXCR5+ CD4+ follicular T-helper-cell numbers were also reduced in all patients. Treatment included immunoglobulin replacement, regular antibiotic prophylaxis, corticosteroids, and steroid-sparing agents. Three patients underwent hematopoietic stem cell transplantation; one of them died due to capillary leak syndrome on day 5 posttransplantation.Conclusion: The disease spectrum of ICOS deficiency is expanding from solely B-cell to combined B- and T-cell immunodeficiency, suggesting genetic and environmental modifiers. Genetic diagnosis is the only tool to distinguish ICOS deficiency from other immunological defects. Patients with antibody deficiency, autoimmunity, and combined immunodeficiency should be screened for ICOS mutations.

AB - Background: Inducible co-stimulator (ICOS) deficiency was the first monogenic defect reported to cause common variable immunodeficiency (CVID)-like disease in 2003. Since then, 16 patients have been reported worldwide with an increasing range of clinical phenotypes.Objective: We sought to compare the clinical and immunological phenotype and provide clinical follow-up and therapeutic approaches for treating ICOS-deficient patients.Methods: We describe the clinical and laboratory data of 15 patients with available clinical data. Previous publications and clinical assessment were used as data sources.Results: The observed ICOS gene mutations were all deletions leading to undetectable protein expression. The clinical phenotype of ICOS deficiency is much broader than initially anticipated and includes not only CVID-like disease but an increased susceptibility to viral and opportunistic infections, as well as cancer. Impaired B-cell development led to decreased memory B-cells in all patients, and hypogammaglobulinemia in all but one patient. Circulating CXCR5+ CD4+ follicular T-helper-cell numbers were also reduced in all patients. Treatment included immunoglobulin replacement, regular antibiotic prophylaxis, corticosteroids, and steroid-sparing agents. Three patients underwent hematopoietic stem cell transplantation; one of them died due to capillary leak syndrome on day 5 posttransplantation.Conclusion: The disease spectrum of ICOS deficiency is expanding from solely B-cell to combined B- and T-cell immunodeficiency, suggesting genetic and environmental modifiers. Genetic diagnosis is the only tool to distinguish ICOS deficiency from other immunological defects. Patients with antibody deficiency, autoimmunity, and combined immunodeficiency should be screened for ICOS mutations.

U2 - 10.3389/fimmu.2017.00964

DO - 10.3389/fimmu.2017.00964

M3 - Article

VL - 8

SP - 964

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - 964

ER -