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@article{1521636,
author = {Kralickova, Pavlina and Milota, Tomas and Litzman, Jiří and Malkusova, Ivana and Jilek, Dalibor and Petanova, Jitka and Vydlakova, Jana and Zimulova, Alena and Fronkova, Eva and Svaton, Michael and Kanderova, Veronika and Bloomfield, Marketa and Parackova, Zuzana and Klocperk, Adam and Haviger, Jiri and Kalina, Tomas and Sediva, Anna},
article_location = {LAUSANNE},
article_number = {3135},
doi = {http://dx.doi.org/10.3389/fimmu.2018.03135},
keywords = {common variable immunodeficiency; malignancy; lymphoma; gastric cancer; whole exome sequencing},
language = {eng},
issn = {1664-3224},
journal = {Frontiers in Immunology},
title = {CVID-Associated Tumors: Czech Nationwide Study Focused on Epidemiology, Immunology, and Genetic Background in a Cohort of Patients With CVID},
url = {http://dx.doi.org/10.3389/fimmu.2018.03135},
volume = {9},
year = {2019}
}
TY - JOUR
ID - 1521636
AU - Kralickova, Pavlina - Milota, Tomas - Litzman, Jiří - Malkusova, Ivana - Jilek, Dalibor - Petanova, Jitka - Vydlakova, Jana - Zimulova, Alena - Fronkova, Eva - Svaton, Michael - Kanderova, Veronika - Bloomfield, Marketa - Parackova, Zuzana - Klocperk, Adam - Haviger, Jiri - Kalina, Tomas - Sediva, Anna
PY - 2019
TI - CVID-Associated Tumors: Czech Nationwide Study Focused on Epidemiology, Immunology, and Genetic Background in a Cohort of Patients With CVID
JF - Frontiers in Immunology
VL - 9
IS - 3135
SP - 1-11
EP - 1-11
PB - FRONTIERS MEDIA SA
SN - 16643224
KW - common variable immunodeficiency
KW - malignancy
KW - lymphoma
KW - gastric cancer
KW - whole exome sequencing
UR - http://dx.doi.org/10.3389/fimmu.2018.03135
L2 - http://dx.doi.org/10.3389/fimmu.2018.03135
N2 - Background: Common variable immunodeficiency disorder (CVID) is one of the most frequent inborn errors of immunity, increased occurrence of malignancies, particularly lymphomas, and gastric cancers, has long been noted among CVID patients. Multifactorial etiology, including immune dysregulation, infections, chronic inflammation, or genetic background, is suggested to contribute to tumor development. Here, we present the results of the first Czech nationwide study focused on epidemiology, immunology and genetic background in a cohort of CVID patients who also developed tumors Methods: The cohort consisted of 295 CVID patients followed for 3,070 patient/years. Standardized incidence ratio (SIR) was calculated to determine the risk of cancer, and Risk ratio (RR) was established to evaluate the significance of comorbidities. Moreover, immunophenotyping, including immunoglobulin levels and lymphocyte populations, was assessed. Finally, Whole exome sequencing (WES) was performed in all patients with lymphoma to investigate the genetic background. Results: Twenty-five malignancies were diagnosed in 22 patients in a cohort of 295 CVID patients. SIR was more than 6 times greater in comparison to the general population. The most common neoplasias were gastric cancers and lymphomas. History of Immune thrombocytopenic purpura (ITP) was established as a potential risk factor, with over 3 times higher risk of cancer development. The B cell count at diagnosis of lymphoma was reduced in the lymphoma group; moreover, post-treatment B and T cell lymphopenia, associated with poorer outcome, was found in a majority of the patients. Intriguingly, no NK cell depression was observed after the chemotherapy. WES revealed heterogeneous genetic background among CVID patients with tumors, identifying gene variants associated with primary immunodeficiencies (such as CTLA4, PIK3CD, PMS2) and/or increased cancer susceptibility (including BRCA1, RABEP1, EP300, KDM5A). Conclusions: The incidence of malignancy in our CVID cohort was found to be more than 6 times greater compared to the general population. Gastric cancers and lymphomas were the most frequently diagnosed tumors. ITP was identified as a risk factor for malignancy in CVID patients. WES analysis confirmed a wide genetic heterogeneity among CVID patients. The identified causative or modifying gene variants pointed to errors in mechanisms contributing to both immunodeficiency and malignancy.
ER -
KRALICKOVA, Pavlina, Tomas MILOTA, Jiří LITZMAN, Ivana MALKUSOVA, Dalibor JILEK, Jitka PETANOVA, Jana VYDLAKOVA, Alena ZIMULOVA, Eva FRONKOVA, Michael SVATON, Veronika KANDEROVA, Marketa BLOOMFIELD, Zuzana PARACKOVA, Adam KLOCPERK, Jiri HAVIGER, Tomas KALINA a Anna SEDIVA. CVID-Associated Tumors: Czech Nationwide Study Focused on Epidemiology, Immunology, and Genetic Background in a Cohort of Patients With CVID. \textit{Frontiers in Immunology}. LAUSANNE: FRONTIERS MEDIA SA, 2019, roč.~9, č.~3135, s.~1-11. ISSN~1664-3224. Dostupné z: https://dx.doi.org/10.3389/fimmu.2018.03135.
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