Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F18%3A10387116" target="_blank" >RIV/00216208:11130/18:10387116 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/18:00105160 RIV/00209775:_____/18:N0000014 RIV/00159816:_____/18:00069163 RIV/00064203:_____/18:10387116

Result on the web

<a href="https://doi.org/10.1016/j.jaci.2018.02.055" target="_blank" >https://doi.org/10.1016/j.jaci.2018.02.055</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jaci.2018.02.055" target="_blank" >10.1016/j.jaci.2018.02.055</a>

Result language

angličtina

Original language name

Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects

Original language description

Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. Objective: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. Methods: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. Results: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16%(n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affectedmutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. Conclusions: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials.

Czech name

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Czech description

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Type

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

CEP classification

—

OECD FORD branch

30102 - Immunology

Project

<a href="/en/project/NV15-30626A" target="_blank" >NV15-30626A: High-throughput genomic profiling for personalised diagnostics and treatment of haematopoietic disorders in children</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

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

—

Volume of the periodical

142

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

1932-1946

UT code for WoS article

000452315800026

EID of the result in the Scopus database

2-s2.0-85048319931