Pavlina Kralickova
@lfhk.cuni.cz/Fakulta
Institute of Clinical Immunology and Allergy, Charles University, Faculty of Medicine in Hradec Kralove
University Hospital Hradec Kralove
RESEARCH INTERESTS
Primary and secondary immunodeficiency
Allergy
Scopus Publications
Scopus Publications
Maria Elena Maccari, Martin Wolkewitz, Charlotte Schwab, Tiziana Lorenzini, Jennifer W. Leiding, Nathalie Aladjdi, Hassan Abolhassani, Wadih Abou-Chahla, Alessandro Aiuti, Saba Azarnoush,et al.
Elsevier BV
Jakub Novosad, Irena Krčmová, Ondřej Souček, Marcela Drahošová, Vratislav Sedlák, Martina Kulířová, and Pavlína Králíčková
MDPI AG
The existence of eosinophils was documented histopathologically in the first half of the 19th century. However, the term “eosinophils” was first used by Paul Ehrlich in 1878. Since their discovery and description, their existence has been associated with asthma, allergies, and antihelminthic immunity. Eosinophils may also be responsible for various possible tissue pathologies in many eosinophil-associated diseases. Since the beginning of the 21st century, the understanding of the nature of this cell population has undergone a fundamental reassessment, and in 2010, J. J. Lee proposed the concept of “LIAR” (Local Immunity And/or Remodeling/Repair), underlining the extensive immunoregulatory functions of eosinophils in the context of health and disease. It soon became apparent that mature eosinophils (in line with previous morphological studies) are not structurally, functionally, or immunologically homogeneous cell populations. On the contrary, these cells form subtypes characterized by their further development, immunophenotype, sensitivity to growth factors, localization, role and fate in tissues, and contribution to the pathogenesis of various diseases, including asthma. The eosinophil subsets were recently characterized as resident (rEos) and inflammatory (iEos) eosinophils. During the last 20 years, the biological therapy of eosinophil diseases, including asthma, has been significantly revolutionized. Treatment management has been improved through the enhancement of treatment effectiveness and a decrease in the adverse events associated with the formerly ultimately used systemic corticosteroids. However, as we observed from real-life data, the global treatment efficacy is still far from optimal. A fundamental condition, “sine qua non”, for correct treatment management is a thorough evaluation of the inflammatory phenotype of the disease. We believe that a better understanding of eosinophils would lead to more precise diagnostics and classification of asthma subtypes, which could further improve treatment outcomes. The currently validated asthma biomarkers (eosinophil count, production of NO in exhaled breath, and IgE synthesis) are insufficient to unveil super-responders among all severe asthma patients and thus give only a blurred picture of the adepts for treatment. We propose an emerging approach consisting of a more precise characterization of pathogenic eosinophils in terms of the definition of their functional status or subset affiliation by flow cytometry. We believe that the effort to find new eosinophil-associated biomarkers and their rational use in treatment algorithms may ameliorate the response rate to biological therapy in patients with severe asthma.
Hana Grombirikova, Viktor Bily, Premysl Soucek, Michal Kramarek, Roman Hakl, Lucie Ballonova, Barbora Ravcukova, Dita Ricna, Karolina Kozena, Lucie Kratochvilova,et al.
Springer Science and Business Media LLC
AbstractHereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare and life-threatening condition characterized by recurrent localized edema. We conducted a systematic screening of SERPING1 defects in a cohort of 207 Czech patients from 85 families with C1-INH-HAE. Our workflow involved a combined strategy of sequencing extended to UTR and deep intronic regions, advanced in silico prediction tools, and mRNA-based functional assays. This approach allowed us to detect a causal variant in all families except one and to identify a total of 56 different variants, including 5 novel variants that are likely to be causal. We further investigated the functional impact of two splicing variants, namely c.550 + 3A > C and c.686-7C > G using minigene assays and RT-PCR mRNA analysis. Notably, our cohort showed a considerably higher proportion of detected splicing variants compared to other central European populations and the LOVD database. Moreover, our findings revealed a significant association between HAE type 1 missense variants and a delayed HAE onset when compared to null variants. We also observed a significant correlation between the presence of the SERPING1 variant c.-21 T > C in the trans position to causal variants and the frequency of attacks per year, disease onset, as well as Clinical severity score. Overall, our study provides new insights into the genetic landscape of C1-INH-HAE in the Czech population, including the identification of novel variants and a better understanding of genotype–phenotype correlations. Our findings also highlight the importance of comprehensive screening strategies and functional analyses in improving the C1-INH-HAE diagnosis and management.
Lucie Ballonová, Přemysl Souček, Peter Slanina, Kamila Réblová, Ondřej Zapletal, Marcela Vlková, Roman Hakl, Viktor Bíly, Hana Grombiříková, Eliška Svobodová,et al.
Frontiers Media SA
Hereditary angioedema (HAE) is a rare genetic disorder with variable expressivity even in carriers of the same underlying genetic defect, suggesting other genetic and epigenetic factors participate in modifying HAE severity. Recent knowledge indicates the role of immune cells in several aspects of HAE pathogenesis, which makes monocytes and macrophages candidates to mediate these effects. Here we combined a search for HAE phenotype modifying gene variants with the characterization of selected genes’ mRNA levels in monocyte and macrophages in a symptom-free period. While no such gene variant was found to be associated with a more severe or milder disease, patients revealed a higher number of dysregulated genes and their expression profile was significantly altered, which was typically manifested by changes in individual gene expression or by strengthened or weakened relations in mutually co-expressed gene groups, depending on HAE severity. SERPING1 showed decreased expression in HAE-C1INH patients, but this effect was significant only in patients carrying mutations supposedly activating nonsense-mediated decay. Pro-inflammatory CXC chemokine superfamily members CXCL8, 10 and 11 were downregulated, while other genes such as FCGR1A, or long non-coding RNA NEAT1 were upregulated in patients. Co-expression within some gene groups (such as an NF-kappaB function related group) was strengthened in patients with a severe and/or mild course compared to controls. All these findings show that transcript levels in myeloid cells achieve different activation or depression levels in HAE-C1INH patients than in healthy controls and/or based on disease severity and could participate in determining the HAE phenotype.
Dita Záveská, Ilona Pospíšilová, Karin Bánszka, Tomáš Freiberger, Hana Grombiříková, and Pavlína Králíčková
Galen, spol. s r.o.
Pavlina Kralickova, Karolina Jankovicova, Ilona Sejkorova, Ondrej Soucek, Katerina Koprivova, Marcela Drahosova, Ctirad Andrys, and Jan Krejsek
S. Karger AG
<b><i>Introduction:</i></b> Reports on the immunogenicity and efficacy of the Spikevax® vaccine against SARS-CoV-2 in immunodeficient patients are still scarce. We aimed to evaluate the safety and immunogenicity of the vaccine in patients with primary humoral immunodeficiency. <b><i>Methods:</i></b> We enrolled 46 patients, including 34 patients with common variable immunodeficiency (CVID), 10 patients with unclassified hypogammaglobulinemia (HypoIg), and 2 patients with X-linked agammaglobulinemia. We collected the blood samples before vaccination (D 0), and 10 days (D +38) and 90 days (D +118) after the second vaccination. Further, we quantified SARS-CoV-2-specific T-cell response (QuantiFERON ELISA test), serum anti-RBD IgG, and anti-RBD IgA-specific antibodies (enzyme immunoassay). <b><i>Results:</i></b> We found that the vaccination elicited predominantly mild adverse events, comparable to healthy population. Vaccination response negatively correlated with a value of Immune Deficiency and Dysregulation Activity in all measured parameters. D +38, seroconversion for anti-RBD IgG and anti-RBD IgA was observed in 65% and 21% CVID patients, respectively. SARS-CoV-2-specific T-cell response was detected in less than 50% of CVID patients. Meanwhile, HypoIg patients had 100%, 90%, and 60% positivity rates for anti-RBD IgG, anti-RBD IgA, and T-cell response, respectively. Three months after the second vaccination, 82% of the responders remained positive for anti-RBD IgG, but only less than 50% remained positive for T-cell activity in CVIDs. Low immunogenicity was observed in patients with lung involvement and/or rituximab treatment history. No SARS-CoV-2 infection was reported within 6 months after the second vaccination. <b><i>Conclusion:</i></b> Spikevax® seems to be safe with satisfactory immunogenicity in patients with primary humoral immunodeficiency.
Roman Hakl, Pavel Kuklínek, Marta Sobotková, Irena Krčmová, Pavlína Králíčková, Martina Vachová, Jana Hanzlíková, Martina Nováčková, Michal Svoboda, Ingrid Kováčová,et al.
Wiley
To the editor, Hereditary angioedema (HAE) is a rare condition which manifests as repeated episodes of localized subcutaneous or submucosal oedema.1 Oedemas involving the upper airways carry the risk of asphyxiation and death. The aim of this study was to present our clinical experience of icatibant and C1 inhibitor use for treating HAE1/2 laryngeal attacks (LA). To our knowledge, this is the first direct comparison of these treatment approaches for LA. A retrospective patient record analysis was performed. Data were collected from the Czech national registry of primary immunodeficiencies, where all known diagnosed HAE patients in Czechia are registered. Data collected between March 2012 and December 2019 were analysed. The attacks were recorded on paper diaries and reported by e-mail, then validated by attending doctors during patients' visits and entered electronically in the registry. Repeated dose/therapy was defined as using the same or another drug within 48 h after the first treatment. Generalized estimating equation (GEE) was used to evaluate differences between treatments with adjustment for potential dependencies among time courses of LA from one individual. Attacks that had missing data on the modelled time courses were excluded from the individual analysis. All analyses were conducted using R version 4.0.4 R Core Team (2021).2 Data from 180 HAE patients (153 HAE1; 26 HAE2; and 1 HAEnC1INH) were available. A total of 5690 attacks were recorded in 153 patients, of which 499 (8.8%) were laryngeal attacks, occurring in 66 patients (40 females and 26 males; 54 HAE1 and 12 HAE2). Another attack location was present in 217 LA, median age at LA was 43.2 (range 5.0– 74.7) years, and triggers were identified in 24.4% of LA (Table 1). Almost all LA (497, 99.6%) were actively treated. Drug use was not randomized but was influenced by patient preference and HAE centre experience. Most attacks, 345 (69.4%), were treated with icatibant (Firazyr®), 94 (18.9%) attacks with recombinant human C1INH (rhC1 INH, Ruconest®), 52 (10.5%) attacks with plasmaderived, pasteurized, nanofiltered C1INH (pnfC1INH, Berinert®) and 2 (0.4%) attacks with plasmaderived, nanofiltered C1INH (nfC1INH, Cynrize®). Because only 2 LA were treated with nfC1INH, the data were not analysed. Three attacks were treated with attenuated androgens and one with fresh frozen plasma, which were also excluded from analysis. In our study, fixed drug doses were used Firazyr® (30 mg), Ruconest® 2100 U 1– 2 vials (median dose 2100 U, range 2100– 4200 U) and Berinert® 500 IU 1– 2 vials (median dose 1000 IU, range 500– 1000 IU). Fortythree patients (65%) with a LA were on longterm prophylaxis (LTP) at the time of the attacks. Two hundred seven (41.6%) LA occurred despite LTP with C1INH (rhC1INH 34 attacks in 2 patients, pnfC1INH 31 attacks in 4 patients), attenuated androgens (119 attacks in 37 patients) and tranexamic acid (58 attacks in 37 patients). In 35 attacks, the patients had been using combined LTP with attenuated androgens and tranexamic acid. This means that 68.6% LA occurred in people taking LTP with attenuated androgens and tranexamic acid, but only 16.4% LA occurred in those using LTP with pnfC1INH and 15% with rhC1INH. Treatment had to be repeated in 71 LA (14.3%), but less frequently in those LA where no other site was affected (6.8%). An adverse reaction associated with the LA treatment was reported in 1 (0.2%) attack. This adverse reaction was evaluated as vasovagal syncope. LA treatment was evaluated as effective in 98.4% of attacks.
Manuel Santamaria, Olaf Neth, Jo A. Douglass, Gergely Krivan, Robin Kobbe, Ewa Bernatowska, Sofia Grigoriadou, Claire Bethune, Anita Chandra, Gerd Horneff,et al.
Springer Science and Business Media LLC
Manuel Santamaria, Olaf Neth, Jo A. Douglass, Gergely Krivan, Robin Kobbe, Ewa Bernatowska, Sofia Grigoriadou, Claire Bethune, Anita Chandra, Gerd Horneff,et al.
Springer Science and Business Media LLC
Abstract Purpose The purpose of this phase 3 study was to evaluate the efficacy, pharmacokinetics (PK), and safety of Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) in patients with primary immunodeficiency (PI). Methods Immunoglobulin treatment-experienced subjects with PI received 52 weeks of IGSC 20% given weekly at the same dose as the subject’s previous IgG regimen (DAF 1:1); the minimum dose was 100 mg/kg/week. The primary endpoint was serious bacterial infections (SBIs [null vs alternative hypothesis: SBI rate per person per year ≥ 1 vs < 1]). IgG subclasses and specific pathogen antibody levels were also measured. Results Sixty-one subjects (19 children [≤ 12 years], 10 adolescents [> 12–16 years], and 32 adults) were enrolled. The rate of SBIs per person per year was 0.017. The 1-sided 99% upper confidence limit was 0.036 (< 1), and the null hypothesis was rejected. The rate of hospitalization due to infection per person per year was 0.017 (2-sided 95% confidence interval: 0.008–0.033) overall. The mean trough total IgG concentrations were comparable to the previous IgG replacement regimen. The average of the individual mean trough ratios (IGSC 20%:previous regimen) was 1.078 (range: 0.83–1.54). The average steady-state mean trough IgG concentrations were 947.64 and 891.37 mg/dL, respectively. Seven subjects had serious treatment-emergent adverse events (TEAEs); none was drug-related. The rate of all TEAEs, including local infusion site reactions, during 3045 IGSC 20% infusions was 0.135. Most TEAEs were mild or moderate. Conclusions IGSC 20% demonstrated efficacy and good safety and tolerability in subjects with PI.
Tomas Milota, Marta Sobotkova, Jitka Smetanova, Marketa Bloomfield, Jana Vydlakova, Zita Chovancova, Jiri Litzman, Roman Hakl, Jiri Novak, Ivana Malkusova,et al.
Frontiers Media SA
Despite the progress in the understanding how COVID-19 infection may impact immunocompromised patients, the data on inborn errors of immunity (IEI) remain limited and ambiguous. Therefore, we examined the risk of severe infection course and hospital admission in a large cohort of patients with IEI. In this multicenter nationwide retrospective survey-based trial, the demographic, clinical, and laboratory data were collected by investigating physicians from 8 national referral centers for the diagnosis and treatment of IEI using a COVID-19-IEI clinical questionnaire. In total, 81 patients with IEI (including 16 with hereditary angioedema, HAE) and confirmed SARS-CoV-2 infection were enrolled, and were found to have a 2.3-times increased (95%CI: 1.44–3.53) risk ratio for hospital admission and a higher mortality ratio (2.4% vs. 1.7% in the general population). COVID-19 severity was associated with the presence of clinically relevant comorbidities, lymphopenia, and hypogammaglobulinemia, but not with age or BMI. No individuals with HAE developed severe disease, despite a hypothesized increased risk due to perturbed bradykinin metabolism. We also demonstrated a high seroconversion rate in antibody-deficient patients and the safety of anti-spike SARS CoV-2 monoclonal antibodies and convalescent plasma. Thus, IEI except for HAE, represent significant risk factors for a severe COVID-19. Therefore, apart from general risk factors, immune system dysregulation may also be involved in the poor outcomes of COVID-19. Despite the study limitations, our results support the findings from previously published trials.
David Egg, Ina Caroline Rump, Noriko Mitsuiki, Jessica Rojas-Restrepo, Maria-Elena Maccari, Charlotte Schwab, Annemarie Gabrysch, Klaus Warnatz, Sigune Goldacker, Virginia Patiño,et al.
Elsevier BV
Marta Sobotkova, Radana Zachova, Roman Hakl, Pavel Kuklinek, Pavlina Kralickova, Irena Krcmova, Jana Hanzlikova, Martina Vachova, and Jirina Bartunkova
S. Karger AG
<b><i>Introduction:</i></b> Acquired angioedema with C1 inhibitor deficiency (AAE-C1-INH) is rare but a potentially life-threatening disease. There are no official prevalence data, nor approved therapies for this condition. <b><i>Objective:</i></b> In this study, we aimed to collect and analyze clinical data on patients with AAE-C1-INH in the Czech Republic. <b><i>Methods:</i></b> We have conducted a retrospective analysis of AAE-C1-INH patients from Czech referral centers for the treatment of hereditary angioedema with C1 inhibitor deficiency. The inclusion criteria involved recurrent episodes of angioedema with the first manifestation at or after the age of 40, negative family history of angioedema, and C1 inhibitor function 50% or less. <b><i>Results:</i></b> A total of 14 patients (7 males and 7 females) met the inclusion criteria for AAE-C1-INH. The median age of the symptom onset was 59.5 years, and the median diagnosis delay was 1 year. The most common clinical manifestation was facial edema (100%) and upper airway swelling (85.7%). All patients responded to the acute attack treatment with icatibant and plasma-derived or recombinant C1 inhibitor concentrate. Lymphoid malignancy was identified in 9 patients (64%), monoclonal gammopathy of uncertain significance in 3 (21%), and in 1 patient autoimmune disease (ulcerative colitis) was considered causative (7%). We were not able to identify any underlying disease only in 1 patient (7%). In 6 of 7 patients (86%) treated for lymphoma, either a reduction in the frequency of angioedema attacks or both angioedema symptoms’ disappearance and complement parameter normalization was observed. <b><i>Conclusions:</i></b> The prevalence of AAE-C1-INH in the Czech Republic is about 1:760,000. This rare condition occurs in approximately 8% of the patients with angioedema with C1 inhibitor deficiency. AAE-C1-INH is strongly associated with lymphoproliferative disorders, and treating these conditions may improve the control of angioedema symptoms.
Tomas Hrncir, Lucia Hrncirova, Miloslav Kverka, Robert Hromadka, Vladimira Machova, Eva Trckova, Klara Kostovcikova, Pavlina Kralickova, Jan Krejsek, and Helena Tlaskalova-Hogenova
MDPI AG
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Its worldwide prevalence is rapidly increasing and is currently estimated at 24%. NAFLD is highly associated with many features of the metabolic syndrome, including obesity, insulin resistance, hyperlipidaemia, and hypertension. The pathogenesis of NAFLD is complex and not fully understood, but there is increasing evidence that the gut microbiota is strongly implicated in the development of NAFLD. In this review, we discuss the major factors that induce dysbiosis of the gut microbiota and disrupt intestinal permeability, as well as possible mechanisms leading to the development of NAFLD. We also discuss the most consistent NAFLD-associated gut microbiota signatures and immunological mechanisms involved in maintaining the gut barrier and liver tolerance to gut-derived factors. Gut-derived factors, including microbial, dietary, and host-derived factors involved in NAFLD pathogenesis, are discussed in detail. Finally, we review currently available diagnostic and prognostic methods, summarise latest knowledge on promising microbiota-based biomarkers, and discuss therapeutic strategies to manipulate the microbiota, including faecal microbiota transplantation, probiotics and prebiotics, deletions of individual strains with bacteriophages, and blocking the production of harmful metabolites.
Pavlína Králíčková and Dita Záveská
Solen s.r.o.
Tomas Milota, Marketa Bloomfield, Pavlina Kralickova, Dalibor Jilek, Vitezslav Novak, Jiri Litzman, Helena Posova, Lucie Mrazova, Jana Poloniova, Miroslav Prucha,et al.
Elsevier BV
Lisanne M. A. Janssen, Roeland W. N. M. Hout, Esther de Vries, Claudio Pignata, Emilia Cirillo, Peter D. Arkwright, Vassilos Lougaris, Matthew Buckland, Marina Garcia‐Prat, Vall d'Hebron,et al.
Wiley
The clinical consequences of isolated decreased serum immunoglobulin (Ig)M are not sufficiently known. Therefore, it is difficult to determine the clinical policy following such a finding. Only few reported IgM‐deficient patients fulfil the European Society for Immunodeficiencies (ESID) diagnostic criteria for selective IgM deficiency (true sIgMdef), or their diagnosis is uncertain due to insufficient laboratory data (possible sIgMdef). Decreased serum IgM is often incidentally found in asymptomatic adults. The objective of our study was to further characterize true sIgMdef and to compare the European data collected through the ESID Registry community (tertiary centres) to our previously published Dutch cohort (secondary centre). Fifteen centres (12 countries) participated with 98 patients. Patients were excluded if serum IgM was only determined once (n = 14), had normalized (n = 8), or if they also had other immunological abnormalities (n = 15). Ten patients (5 adults) completely fulfilled the ESID criteria for true sIgMdef. Age‐matched cut‐off values varied widely between centres; when using the ESID diagnostic protocol reference values, only six patients (five adults) had true sIgMdef. Because of these small numbers, further analyses were performed in patients with true or possible sIgMdef (13 adults, 48 children). Respiratory infections were commonly reported at presentation (adults 54%, children 60%). Symptomatic adults had lower serum IgM levels (mean 0.27 g/L, 95% CI 0.22‐0.31) than those without symptoms (mean 0.33 g/L, 95% CI 0.30‐0.36; P = 0.02). To be able to explore the clinical consequences of true sIgMdef, we should fully analyse and accurately describe those patients in whom a decreased serum IgM is found.
Kristýna Fiedorová, Matěj Radvanský, Juraj Bosák, Hana Grombiříková, Eva Němcová, Pavlína Králíčková, Michaela Černochová, Iva Kotásková, Matej Lexa, Jiří Litzman,et al.
Frontiers Media SA
Common Variable Immunodeficiency (CVID) is the most frequent symptomatic immune disorder characterized by reduced serum immunoglobulins. Patients often suffer from infectious and serious non-infectious complications which impact their life tremendously. The monogenic cause has been revealed in a minority of patients so far, indicating the role of multiple genes and environmental factors in CVID etiology. Using 16S and ITS rRNA amplicon sequencing, we analyzed the bacterial and fungal gut microbiota, respectively, in a group of 55 participants constituting of CVID patients and matched healthy controls including 16 case-control pairs living in the same household, to explore possible associations between gut microbiota composition and disease phenotype. We revealed less diverse and significantly altered bacterial but not fungal gut microbiota in CVID patients, which additionally appeared to be associated with a more severe disease phenotype. The factor of sharing the same household impacted both bacterial and fungal microbiome data significantly, although not as strongly as CVID diagnosis in bacterial assessment. Overall, our results suggest that gut bacterial microbiota is altered in CVID patients and may be one of the missing environmental drivers contributing to some of the symptoms and disease severity. Paired samples serving as controls will provide a better resolution between disease-related dysbiosis and other environmental confounders in future studies.
Pavlina Kralickova, Tomas Milota, Jiri Litzman, Ivana Malkusova, Dalibor Jilek, Jitka Petanova, Jana Vydlakova, Alena Zimulova, Eva Fronkova, Michael Svaton,et al.
Frontiers Media SA
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.
Roman Hakl, Pavel Kuklínek, Irena Krčmová, Pavlína Králíčková, Tomáš Freiberger, Petr Janků, Marcela Vlková, and Jiří Litzman
Springer Science and Business Media LLC
Zita Chovancova, Pavlina Kralickova, Alena Pejchalova, Marketa Bloomfield, Jana Nechvatalova, Marcela Vlkova, and Jiri Litzman
Springer Science and Business Media LLC