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المؤلفون: Králíčková, Pavlína, Malá, Eva, Vokurková, Doris, Souček, Ondřej, Krčmová, Irena, Hrnčíř, Zbyněk
المساهمون: Králíčková, Pavlína, Malá, Eva, Vokurková, Doris , 1958-, Souček, Ondřej, Krčmová, Irena , 1957-, Hrnčíř, Zbyněk , 1933-
المصدر: Vnitřní lékařství : orgán Československé společnosti pro vnitřní lékařství, sekce Československé lékařské společnosti J. E. Purkyně | 2015 Volume:61 | Number:9
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3دورية أكاديمية
المؤلفون: Grombirikova, Hana, Bily, Viktor, Soucek, Premysl, Kramarek, Michal, Hakl, Roman, Ballonova, Lucie, Ravcukova, Barbora, Ricna, Dita, Kozena, Karolina, Kratochvilova, Lucie, Sobotkova, Marta, Zachova, Radana, Kuklinek, Pavel, Kralickova, Pavlina, Krcmova, Irena, Hanzlikova, Jana, Vachova, Martina, Krystufkova, Olga, Dankova, Eva, Jesenak, Milos, Novackova, Martina, Svoboda, Michal, Litzman, Jiri, Freiberger, Tomas
المساهمون: Ministerstvo Zdravotnictví Ceské Republiky, Ministerstvo Školství, Mládeže a Tělovýchovy, Masaryk University
المصدر: Journal of Clinical Immunology ; volume 43, issue 8, page 1974-1991 ; ISSN 0271-9142 1573-2592
مصطلحات موضوعية: Immunology, Immunology and Allergy
الوصف: Hereditary 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.
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4رسالة جامعية
المؤلفون: Králíčková, Pavlína
مرشدي الرسالة: Melichar, Bohuslav, Tesařová, Petra, Litzman, Jiří
الوصف: Laboratory parameters in the detection of the effect of anticancer therapy on immune system Summary We can consider the immune response to cancer cells as the last barrier in carcinogenesis. Chemotherapeutics interfere directly or indirectly with tumour microenvironment. Our work was divided into two parts. The aim of our study was to describe the distribution of lymphocyte subsets in peripheral blood and urinary neopterin in breast cancer patients in relatation to the treatment in the part one, and elucidate the correlation between CD14+CD16+ monocytes, urinary neopterin and risk factors of atherosclerosis in the part two. We show that the changes of lymphocyte subpopulations are present even at the time of cancer diagnosis. The treatment could positively affect the anticancer response. The changes of these lymphocytes subsets during therapy in patients with metastatic stage of disease are less expressed. The restoration of the immune system is a long-term process. The systemic inflammatory response connected with tumour presence could contribute to the accented atherosclerosis, possible long-term complication in cancer patients.
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5دورية أكاديمية
المؤلفون: Santamaria, Manuel, Neth, Olaf, Douglass, Jo A, Krivan, Gergely, Kobbe, Robin, Bernatowska, Ewa, Grigoriadou, Sofia, Bethune, Claire, Chandra, Anita, Horneff, Gerd, Borte, Michael, Sonnenschein, Anja, Kralickova, Pavlina, Ramón, Silvia Sánchez, Langguth, Daman, Gonzalez-Granado, Luis Ignacio, Alsina, Laia, Querolt, Montse, Griffin, Rhonda, Hames, Carrie, Mondou, Elsa, Price, Jeffrey, Sanz, Ana, Lin, Jiang
مصطلحات موضوعية: 20% immunoglobulin, GTI1503, Primary immunodeficiency, immunoglobulin replacement therapy, subcutaneous, Adolescent, Adult, Child, Humans, Immunoglobulin G, Immunoglobulins, Intravenous, Immunologic Deficiency Syndromes, Immunologic Factors, Infusions
الوصف: 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). 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 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 ( 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 ( IGSC 20% demonstrated efficacy and good safety and tolerability in subjects with PI.
وصف الملف: application/pdf
العلاقة: http://hdl.handle.net/10668/20596Test; PMC9016006; https://link.springer.com/content/pdf/10.1007/s10875-021-01181-6.pdfTest; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016006/pdfTest
الإتاحة: https://doi.org/10.1007/s10875-021-01181-6Test
http://hdl.handle.net/10668/20596Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016006/pdfTest -
6دورية أكاديمية
المؤلفون: Santamaria, Manuel, Neth, Olaf, Douglass, Jo A, Krivan, Gergely, Kobbe, Robin, Bernatowska, Ewa, Grigoriadou, Sofia, Bethune, Claire, Chandra, Anita, Horneff, Gerd, Borte, Michael, Sonnenschein, Anja, Kralickova, Pavlina, Ramón, Silvia Sánchez, Langguth, Daman D, Gonzalez-Granado, Luis Ignacio, Alsina, Laia, Querolt, Montse, Griffin, Rhonda, Hames, Carrie, Mondou, Elsa, Price, Jeffrey, Sanz, Ana, Lin, Jiang
وصف الملف: application/pdf
العلاقة: http://hdl.handle.net/10668/20607Test; PMC9015977; https://link.springer.com/content/pdf/10.1007/s10875-022-01219-3.pdfTest; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015977/pdfTest
الإتاحة: https://doi.org/10.1007/s10875-022-01219-3Test
http://hdl.handle.net/10668/20607Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015977/pdfTest -
7دورية أكاديمية
المؤلفون: Egg, David, Rump, Ina Caroline, Mitsuiki, Noriko, Rojas-Restrepo, Jessica, Maccari, Maria-Elena, Schwab, Charlotte, Gabrysch, Annemarie, Warnatz, Klaus, Goldacker, Sigune, Patiño, Virginia, Wolff, Daniel, Okada, Satoshi, Hayakawa, Seiichi, Shikama, Yoshiaki, Kanda, Kenji, Imai, Kohsuke, Sotomatsu, Manabu, Kuwashima, Makoto, Kamiya, Takahiro, Morio, Tomohiro, Matsumoto, Kazuaki, Mori, Takeshi, Yoshimoto, Yuri, Dybedal, Ingunn, Kanariou, Maria, Kucuk, Zeynep Yesim, Chapdelaine, Hugo, Petruzelkova, Lenka, Lorenz, Hanns-Martin, Sullivan, Kathleen E, Heimall, Jennifer, Moutschen, Michel, Litzman, Jiri, Recher, Mike, Albert, Michael H, Hauck, Fabian, Seneviratne, Suranjith, Pachlopnik Schmid, Jana, Kolios, Antonios, Unglik, Gary, Klemann, Christian, Snapper, Scott, Giulino-Roth, Lisa, Svaton, Michael, Platt, Craig D, Hambleton, Sophie, Neth, Olaf, Gosse, Geraldine, Reinsch, Steffen, Holzinger, Dirk, Kim, Yae-Jean, Bakhtiar, Shahrzad, Atschekzei, Faranaz, Schmidt, Reinhold, Sogkas, Georgios, Chandrakasan, Shanmuganathan, Rae, William, Derfalvi, Beata, Marquart, Hanne Vibeke, Ozen, Ahmet, Kiykim, Ayca, Karakoc-Aydiner, Elif, Králíčková, Pavlína, de Bree, Godelieve, Kiritsi, Dimitra, Seidel, Markus G, Kobbe, Robin, Dantzer, Jennifer, Alsina, Laia, Armangue, Thais, Lougaris, Vassilios, Agyeman, Philipp, Nyström, Sofia, Buchbinder, David, Arkwright, Peter D, Grimbacher, Bodo
المصدر: Journal of Allergy and Clinical Immunology, 149 (2), 736 - 746 (2022)
مصطلحات موضوعية: CTLA-4, HSCT, LRBA, abatacept, common variable immunodeficiency, diagnosis, primary immunodeficiency, rituximab, sirolimus, treatment, CTLA-4 Antigen, CTLA4 protein, human, Adolescent, Adult, Agammaglobulinemia/etiology, Aged, Autoimmune Diseases/etiology, CTLA-4 Antigen/deficiency, CTLA-4 Antigen/genetics, Child, Preschool, Female, Genetic Association Studies, Hematopoietic Stem Cell Transplantation, Humans, Immunologic Deficiency Syndromes/complications, Immunologic Deficiency Syndromes/genetics, Immunologic Deficiency Syndromes/therapy, Infant
الوصف: peer reviewed ; 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.
العلاقة: https://www.jacionline.org/article/S0091-6749Test(21)00891-5/fulltext; urn:issn:0091-6749; urn:issn:1097-6825; https://orbi.uliege.be/handle/2268/308264Test; info:hdl:2268/308264; https://orbi.uliege.be/bitstream/2268/308264/1/PIIS0091674921008915.pdfTest; scopus-id:2-s2.0-85109673099; info:pmid:34111452
الإتاحة: https://doi.org/10.1016/j.jaci.2021.04.039Test
https://orbi.uliege.be/handle/2268/308264Test
https://orbi.uliege.be/bitstream/2268/308264/1/PIIS0091674921008915.pdfTest -
8دورية أكاديمية
المؤلفون: Kralickova, Pavlina, Jankovicova, Karolina, Sejkorova, Ilona, Soucek, Ondrej, Koprivova, Katerina, Drahosova, Marcela, Andrys, Ctirad, Krejsek, Jan
المصدر: International Archives of Allergy and Immunology ; volume 183, issue 12, page 1297-1310 ; ISSN 1018-2438 1423-0097
مصطلحات موضوعية: Immunology, General Medicine, Immunology and Allergy
الوصف: Introduction: 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. Methods: 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). Results: 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. Conclusion: Spikevax® seems to be safe with satisfactory immunogenicity in patients with primary humoral immunodeficiency.
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9دورية أكاديمية
المؤلفون: Milota, Tomas, Sobotkova, Marta, Smetanova, Jitka, Bloomfield, Marketa, Vydlakova, Jana, Chovancova, Zita, Litzman, Jiri, Hakl, Roman, Novak, Jiri, Malkusova, Ivana, Hanzlikova, Jana, Jilek, Dalibor, Hutyrova, Beata, Novak, Vitezslav, Krcmova, Irena, Sediva, Anna, Kralickova, Pavlina
المساهمون: Agentura Pro Zdravotnický Výzkum České Republiky
المصدر: Frontiers in Immunology ; volume 13 ; ISSN 1664-3224
مصطلحات موضوعية: Immunology, Immunology and Allergy
الوصف: 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.
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10دورية أكاديمية
المؤلفون: Sobotkova, Marta, Zachova, Radana, Hakl, Roman, Kuklinek, Pavel, Kralickova, Pavlina, Krcmova, Irena, Hanzlikova, Jana, Vachova, Martina, Bartunkova, Jirina
المصدر: International Archives of Allergy and Immunology ; volume 182, issue 7, page 642-649 ; ISSN 1018-2438 1423-0097
الوصف: Introduction: 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. Objective: In this study, we aimed to collect and analyze clinical data on patients with AAE-C1-INH in the Czech Republic. Methods: 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. Results: 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. Conclusions: 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.
