Severe combined immunodeficiency (SCID) screening je souhrnný název pro nástroj časné detekce řady závažných vrozených poruch imunity. Současná kvantifikace excizních DNA molekul TREC a KREC umožňuje časně diagnostikovat závažné buněčné i protilátkové vrozené defekty imunity. Do dvouletého pilotního programu screeningu se v letech 2022–2023 v České republice zapojilo > 90 % novorozenců (vyšetřeno bylo 198 675 vzorků). Diagnostikováni byli 2 pacienti se SCID na podkladě CD3 epsilon deficience a atypického kompletního DiGeorgova syndromu a dalších 17 pacientů s jinými vrozenými poruchami imunity, z toho 9 s agamaglobulinemií. U dvou pacientů se SCID umožnil screening časnou kauzální terapii, tj. transplantaci hematopoetických buněk / thymu, u non-SCID pacientů vedla časná znalost jejich diagnózy k zavedení adekvátních režimových a profylaktických opatření za účelem snížení jejich následné morbidity. Od 1. ledna 2024 byl screening závažných vrozených poruch imunity spolu se spinální muskulární atrofií integrován do celoplošného novorozeneckého laboratorního screeningu.
Severe Combined Immunodeficiency (SCID) screening is a collective term for an early detection tool for a range of serious inborn errors of immunity. The quantification of excision DNA molecules TREC and KREC allows for early diagnosis of severe cellular and antibody immune defects. The recently concluded Czech pilot screening program (2022-2023) included over 90% of newborns (with 198,675 samples examined). Two patients with SCID were diagnosed based on CD3 epsilon deficiency and atypical complete DiGeorge syndrome, and another 17 patients were found to have other inborn errors of immunity, including 9 agammaglobulinemia. Screening enabled early causal therapy, i.e., hematopoietic cell/thymus transplantation, for two SCID patients, while early diagnosis in non-SCID patients led to the implementation of appropriate regimen and prophylactic measures to reduce subsequent morbidity. As of January 1, 2024, screening for severe inborn errors of immunity, along with screening for spinal muscular atrophy, becomes integral part of the national laboratory newborn screening program.
- MeSH
- agamaglobulinemie diagnóza farmakoterapie genetika MeSH
- kojenec MeSH
- kombinovaná protilátková terapie terapeutické užití MeSH
- lidé MeSH
- novorozenecký screening MeSH
- předškolní dítě MeSH
- primární imunodeficience * diagnóza genetika terapie MeSH
- těžká kombinovaná imunodeficience diagnóza genetika terapie MeSH
- thymus abnormality patologie MeSH
- transplantace hematopoetických kmenových buněk metody MeSH
- transplantace orgánů MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- kazuistiky MeSH
Atopická dermatitida je chronické onemocnění, které může významně ovlivnit kvalitu života nejen dětského pacienta, ale i celé rodiny. Vyžaduje časově náročnou lokální léčbu. Dosavadní možnosti celkové léčby nebyly zcela uspokojivé, zejména z důvodu širokospektré imunosuprese a častých nežádoucích účinků. Článek představuje aktuálně dostupné možnosti cílené léčby tohoto zánětlivého kožního onemocnění.
Atopic dermatitis is a chronic skin condition with serious impact on life of pediatric patient and his family. Local treatment is time consuming and often not well tolerated. Previous systemic treatment possibilities were not satisfactory especially due to broad spectrum immunosuppression and its side effects. The article shows the possibilities of new targeted treatment of this inflammatory skin disease.
- Klíčová slova
- Dupilumab,
- MeSH
- atopická dermatitida * diagnóza farmakoterapie MeSH
- dítě MeSH
- ekzém etiologie farmakoterapie imunologie klasifikace MeSH
- humanizované monoklonální protilátky * farmakologie klasifikace terapeutické užití MeSH
- lidé MeSH
- receptor interleukinu-4 - alfa-podjednotka antagonisté a inhibitory terapeutické užití MeSH
- superinfekce klasifikace mikrobiologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
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.
- MeSH
- hereditární angioedémy * diagnóza epidemiologie genetika MeSH
- inhibiční protein komplementu C1 * genetika MeSH
- lidé MeSH
- messenger RNA MeSH
- sestřih RNA MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
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.
- Publikační typ
- časopisecké články MeSH
Popisujeme případ chlapce s těžkou atopickou dermatitidou, refrakterní na systémovou imunosupresivní léčbu, s poruchou růstu, sekundárním hypokortikalismem po opakovaném podání systémových kortikosteroidů. V léčbě jsme s úspěchem podali monoklonální protilátku proti alfa podjednotce receptoru pro interleukin 4 (IL-4Rα) dupilumab.
We are presenting a case report of a boy with severe atopic dermatitis refractory to systemic immunosupresive treatment with growth retardation, secondary hypocorticalism after repeated systemic corticotherapy. Treatment with monoclonal antibody inhibiting alpha subunit of interleukin 4 receptor (IL-4Rα) dupilumab was successfull.
Activated phosphoinositide 3-kinase delta syndrome (APDS), caused by mutations in PI3Kδ catalytic p110δ (PIK3CD) or regulatory p85α (PIK3R1) subunits, is a primary immunodeficiency affecting both humoral and cellular immunity, which shares some phenotypic similarities with hyper-IgM syndromes and common variable immunodeficiency (CVID). Since its first description in 2013, over 200 patients have been reported worldwide. Unsurprisingly, many of the newly diagnosed patients were recruited later in life from previously long-standing unclassified immunodeficiencies and the early course of the disease is, therefore, often less well-described. In this study, we report clinical and laboratory features of eight patients followed for APDS, with particular focus on early warning signs, longitudinal development of their symptoms, individual variations, and response to therapy. The main clinical features shared by our patients included recurrent bacterial and viral respiratory tract infections, gastrointestinal disease, non-malignant lymphoproliferation, autoimmune thyroiditis, and susceptibility to EBV. All patients tolerated vaccination with both attenuated live and subunit vaccines with no adverse effects, although some failed to mount adequate antibody response. Laboratory findings were characterized by dysgammaglobulinaemia, elevated serum IgM, block in B-cell maturation with high transitional B cells, and low naïve T cells with CD8 T-cell activation. All patients benefited from immunoglobulin replacement therapy, whereas immunosuppression with mTOR pathway inhibitors was only partially successful. Therapy with specific PI3K inhibitor leniolisib was beneficial in all patients in the clinical trial. These vignettes, summary data, and particular tell-tale signs should serve to facilitate early recognition, referral, and initiation of outcome-improving therapy.
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- biologické markery MeSH
- dospělí MeSH
- hereditární angioedémy diagnóza epidemiologie etiologie terapie MeSH
- inhibiční protein komplementu C1 genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- management nemoci MeSH
- náchylnost k nemoci MeSH
- ochrana veřejného zdraví MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- určení symptomu MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- esterasy MeSH
- hereditární angioedémy * farmakoterapie prevence a kontrola MeSH
- inhibiční protein komplementu C1 * terapeutické užití MeSH
- komplement C1 - inaktivátory MeSH
- lidé MeSH
- rekombinantní proteiny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
V České republice nebyla dosud k dispozici populační data týkající se alergie na vejce u kojenců a malých dětí, klinických projevů této alergie, vztahu k atopickému ekzému a atopickému pochodu. U námi sledovaných pacientů jsme ověřili, že alergie na vejce je úzce spjata s časným nástupem alergických symptomů, těžkými projevy atopického ekzému, senzibilizací k inhalačním alergenům a nástupem alergické rýmy a/nebo astmatu.
Population study on egg allergy in infants and small children, characterisation of its clinical symptoms and its relation to atopic eczema and to the natural course of atopic march, has not been published yet in the Czech Republic. In our cohort we proved that the egg allergy is closely linked to the early onset of allergic symptoms, to a severe form of atopic eczema, to a sensibilization to inhaled allergens with the presence of allergic rhinitis and/or allergic asthma.
- MeSH
- alergie na arašídy etiologie MeSH
- alergie na vejce * dietoterapie imunologie patofyziologie MeSH
- epidemiologické studie MeSH
- imunoglobulin E imunologie MeSH
- imunologické testy metody MeSH
- kohortové studie MeSH
- kojenec MeSH
- kožní manifestace MeSH
- lidé MeSH
- potravinová alergie patofyziologie terapie MeSH
- respirační alergie MeSH
- stupeň závažnosti nemoci MeSH
- vejce škodlivé účinky MeSH
- věk při počátku nemoci MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
