Therapeutic options for CTLA-4 insufficiency

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F22%3A00075886" target="_blank" >RIV/00159816:_____/22:00075886 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/22:10428364 RIV/00216208:11130/22:10428364 RIV/00216208:11150/22:10428364 RIV/00179906:_____/22:10428364 RIV/00216224:14110/22:00125671

Result on the web

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0091674921008915?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0091674921008915?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jaci.2021.04.039" target="_blank" >10.1016/j.jaci.2021.04.039</a>

Result language

angličtina

Original language name

Therapeutic options for CTLA-4 insufficiency

Original language description

Background: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness. Objective: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level. Methods: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated. Results: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed. Conclusion: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30200 - Clinical medicine

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Allergy and Clinical Immunology

ISSN

0091-6749

e-ISSN

1097-6825

Volume of the periodical

149

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

736-746

UT code for WoS article

000752623200031

EID of the result in the Scopus database

—