• MeSH
• běžná variabilní imunodeficience diagnóza   etiologie   komplikace   mortalita   patologie   MeSH
• diferenciální diagnóza MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * diagnostické zobrazování   farmakoterapie   krev   mortalita   patologie   MeSH
• paraproteinemie krev   MeSH
• sepse diagnóza   farmakoterapie   komplikace   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.

• MeSH
• běžná variabilní imunodeficience patologie   MeSH
• bronchiektazie patologie   MeSH
• bronchy patologie   MeSH
• dítě MeSH
• dospělí MeSH
• hrudní stěna patologie   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• počítačová rentgenová tomografie metody   MeSH
• předškolní dítě MeSH
• senioři MeSH
• spirometrie metody   MeSH
• syndromy imunologické nedostatečnosti patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Oproti běžným představám se problematika primárních imunodeficiencí zdaleka netýká pouze pediatrie, velký počet primárně imunodeficitních pacientů je nejen léčen, ale i diagnostikován v dospělém věku. Nejdůležitější manifestací těchto chorob jsou závažné, neobvyklé nebo špatně léčitelné infekce. Některé choroby z primární imunodeficience se často manifestují až v dospělém věku - jedná se především o hypogamaglobulinemii označovanou jako běžná variabilní imunodeficience (CVID) a Goodův syndrom (hypogamaglobulinemie s tymomem). Díky úspěšné léčbě se dospělosti dožívají (a často vedou "normální" život) i ti nemocní, jejichž manifestace začala v časném dětství. I mezi nimi jsou nejčastější nemocní s poruchami tvorby protilátek - např. s X-vázanou agamaglobulinemií, ale také nemocní s Di Georgeovým syndromem (porucha vývoje tymu, srdce, paratyreoidey). Důležitou skupinou jsou i nemocní s hereditárním angioedémem (deficit C1-INH), tito nemocní netrpí zvýšeným výskytem infekcí, objevují se u nich však otoky podkoží a sliznic.

In contrast to general opinion, the issue of primary immunodeficiency is far from just a pediatric medicine; a large number of patients with primary immunodefciencies are not only treated, but also diagnosed in adulthood. The most important manifestation of these diseases are serious, unusual or ill-treatable infections. Some primary immune deficiency diseases manifest themselves in adulthood - mainly common variable immunodeficiency (CVID) and Good´s syndrome (hypogammaglobulinemia with thymoma). Due to successful treatment, adults also suffer from illnesses manifestation of which begin in early infancy. Among these, the most common are patients with disorders of antibody production - for example, X-linked agammaglobulinemia or T-cell defect - Di George syndrome (thymus deficiency, morphological heart abnormalities, hypoparathyroidism). Another important group of primary immunodeficiencies are patients with hereditary angioedema (C1-INH deficiency). These patients do not suffer from an increased incidence of infections, but from swelling of the subcutaneous and submucosal tissues.

• MeSH
• běžná variabilní imunodeficience * patologie   terapie   MeSH
• DiGeorgeův syndrom diagnóza   komplikace   MeSH
• hereditární angioedémy * diagnóza   terapie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• adaptorové proteiny signální transdukční genetika   imunologie   nedostatek   MeSH
• antigen CTLA-4 nedostatek   MeSH
• autoimunitní nemoci diagnostické zobrazování   imunologie   patologie   MeSH
• autoprotilátky analýza   MeSH
• běžná variabilní imunodeficience * genetika   imunologie   patologie   MeSH
• celiakie imunologie   MeSH
• enteritida imunologie   patologie   MeSH
• fenotyp MeSH
• fosfatidylinositol-3-kinasy třídy I genetika   imunologie   MeSH
• gastroenteritida imunologie   mikrobiologie   MeSH
• gastrointestinální nemoci imunologie   mikrobiologie   MeSH
• genetická predispozice k nemoci MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé MeSH
• splenomegalie imunologie   MeSH
• Check Tag
• lidé MeSH

Common variable immunodeficiency (CVID) is the most frequent clinically relevant primary immunodeficiency and shows enormous heterogeneity in clinical presentation. Despite clinical immunodeficiency, opportunistic infections are not a typical manifestation of CVID. A retrospective study of 32 patients followed up for 335 patient-years was performed to determine the frequency of cytomegalovirus (CMV) disease. Symptomatic CMV infection was documented in 3 CVID patients. Patients No. 1 and 2 suffered from CMV pneumonia, with complications due to atypical mycobacteriosis in patient No. 1. Patient No. 3 suffered from CMV enteritis. A history of cancer and chronic hepatitis C infection (patient No. 1), immunosuppressive therapy for interstitial lung disease (patient No. 2) and serious enteropathy complicated with malnutrition (patient No. 3) may have contributed to the complications despite only mild abnormalities in T-cell subpopulations. The direct detection of CMV in bronchoalveolar lavage, stool or tissue samples was the most beneficial diagnostic laboratory method, whereas the detection of CMV DNA in blood did not produce positive results. Adequate treatment of CMV disease led to significant clinical improvement in all 3 patients. The frequency of CMV disease appears to be higher than previously described. In our experience, the probability of opportunistic infections in CVID patients increases with secondary comorbidities and their management.

• MeSH
• atypické mykobakteriální infekce komplikace   diagnóza   patologie   virologie   MeSH
• běžná variabilní imunodeficience komplikace   diagnóza   patologie   virologie   MeSH
• bronchoalveolární lavážní tekutina virologie   MeSH
• cytomegalovirové infekce komplikace   diagnóza   patologie   virologie   MeSH
• Cytomegalovirus MeSH
• DNA virů izolace a purifikace   MeSH
• enteritida komplikace   diagnóza   patologie   virologie   MeSH
• feces virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• virová pneumonie komplikace   diagnóza   patologie   virologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

Článek shrnuje diagnostická kritéria, etiopatogenezi, klinické projevy a léčbu primárních i sekundárních poruch tvorby protilátek. Humorální imunodeficity obecně spojuje náchylnost k infekcím způsobeným opouzdřenými baktériemi. Dominují infekce dýchacích cest a trávicího ústrojí. U řady klinických jednotek je zvýšená náchylnost k autoimunitním či alergickým onemocněním. Základem léčby jsou substituce imunoglobuliny a cílená antibiotická terapie. Díky včasnější diagnostice a lepší dostupnosti léčby se prognóza i kvalita života těchto nemocných výrazně zlepšily.

The article summarises diagnostic criteria, etiopathogenesis, clinical symptoms, and management of primary and secondary humoural immunodeficiencies. Humoural immunodeficiencies are connected with higher susceptibility to infections caused by encapsulated bacteria. Infections of respiratory and gastrointestinal tract have been predominant. There is also a trend to autoimmune complications and allergies in patients with this diagnosis. The therapy is based on immunoglobulin substitution and targeted antibiotic treatment. Due to earlier diagnosis and better availability of therapeutic options in recent years, the prognosis of patients with primary immunodeficiencies and their quality of life has improved significantly.

• Klíčová slova
• XLA, CVID, humorální, imunodeficience,
• MeSH
• agamaglobulinemie * diagnóza   etiologie   genetika   MeSH
• běžná variabilní imunodeficience genetika   klasifikace   patologie   MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• dospělí MeSH
• dysgamaglobulinemie * diagnóza   klasifikace   terapie   MeSH
• lidé MeSH
• prognóza MeSH
• protilátky MeSH
• syndromy imunologické nedostatečnosti * diagnóza   klasifikace   terapie   MeSH
• thymom komplikace   terapie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH

The neonatal Fc receptor (FcRn) acts as a key regulator of IgG homeostasis and is an important sensor of luminal infection. We analyzed the influence of FcRn expression on disease phenotype and the catabolism of therapeutically administered intravenous immunoglobulins (IVIG) in 28 patients with common variable immunodeficiency (CVID). Patients with generalized bronchiectasis and fibrosis had lower levels of FCRN mRNA compared to patients without these complications (P=0.027 and P=0.041, respectively). Moreover, FCRN mRNA levels correlated negatively with the extent of bronchiectasis and the rate of IgG decline after infusion of IVIG (P=0.027 and P=0.045, respectively). No relationship of FCRN expression with age at disease onset, age at diagnosis, diagnostic delay, IgG levels or frequency of infections before or during replacement immunoglobulin treatment, the presence of lung functional abnormalities, chronic diarrhea, granulomas, lymphadenopathy, splenomegaly or autoimmune phenomena was observed. Our results showed that FcRn might play a role in the development of lung structural abnormalities and in the catabolism of IVIG in patients with CVID.

• MeSH
• běžná variabilní imunodeficience genetika   imunologie   patologie   patofyziologie   MeSH
• dospělí MeSH
• exprese genu MeSH
• fenotyp MeSH
• imunoglobulin G krev   MeSH
• intravenózní imunoglobuliny krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• MHC antigeny I. třídy genetika   MeSH
• minisatelitní repetice MeSH
• mladiství MeSH
• mladý dospělý MeSH
• plíce imunologie   patologie   patofyziologie   MeSH
• promotorové oblasti (genetika) MeSH
• receptory Fc genetika   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Increased proportions of naive B cell subset and B cells defined as CD27(neg)CD21(neg)CD38(neg) are frequently found in patients with common variable immunodeficiency (CVID) syndrome. Current methods of polychromatic flow cytometry and PCR-based detection of k deletion excision circles allow for fine definitions and replication history mapping of infrequent B cell subsets. We have analyzed B cells from 48 patients with CVID and 49 healthy controls to examine phenotype, frequency, and proliferation history of naive B cell subsets. Consistent with previous studies, we have described two groups of patients with normal (CVID-21norm) or increased (CVID-21lo) proportions of CD27(neg)CD21(neg)CD38(neg) B cells. Upon further analyses, we found two discrete subpopulations of this subset based on the expression of CD24. The B cell subsets showed a markedly increased proliferation in CVID-21lo patients as compared with healthy controls, suggesting developmental arrest rather than increased bone marrow output. Furthermore, when we analyzed CD21(pos) naive B cells, we found two different subpopulations based on IgM and CD24 expression. They correspond to follicular (FO) I and FO II cells previously described in mice. FO I subset is significantly underrepresented in CVID-21lo patients. A comparison of the replication history of naive B cell subsets in CVID patients and healthy controls implies refined naive B cell developmental scheme, in which human transitional B cells develop into FO II and FO I. We propose that the CD27(neg)CD21(neg)CD38(neg) B cells increased in some of the CVID patients originate from the two FO subsets after loss of CD21 expression.

• MeSH
• antigen CD24 * biosyntéza   genetika   MeSH
• běžná variabilní imunodeficience * imunologie   metabolismus   patologie   MeSH
• buněčná diferenciace imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• G0 fáze * imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• počet lymfocytů MeSH
• podskupiny B-lymfocytů imunologie   klasifikace   patologie   MeSH
• proliferace buněk MeSH
• regulace genové exprese * imunologie   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

The European Common Variable Immunodeficiency Disorders registry was started in 1996 to define distinct clinical phenotypes and determine overlap within individual patients. A total of 7 centers contributed patient data, resulting in the largest cohort yet reported. Patients (334), validated for the diagnosis, were followed for an average of 25.6 years (9461 patient-years). Data were used to define 5 distinct clinical phenotypes: no complications, autoimmunity, polyclonal lymphocytic infiltration, enteropathy, and lymphoid malignancy. A total of 83% of patients had only one of these phenotypes. Analysis of mortality showed a considerable reduction in the last 15 years and that different phenotypes were associated with different survival times. Types of complications and clinical phenotypes varied significantly between countries, indicating the need for large, international registries. Ages at onset of symptoms and diagnosis were shown to have a Gaussian distribution, but were not useful predictors of phenotype. The only clinical predictor was polyclonal lymphocytic infiltration, which was associated with a 5-fold increased risk of lymphoid malignancy. There was widespread variation in the levels of serum immunoglobulin isotypes as well as in the percentages and absolute numbers of B cells, confirming the heterogeneity of these conditions. Higher serum IgM and lower circulating CD8 proportions were found to be predictive markers for polyclonal lymphocytic infiltration and autoimmunity, respectively.

• MeSH
• autoimunita MeSH
• běžná variabilní imunodeficience * klasifikace   komplikace   mortalita   patologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• fenotyp MeSH
• imunoglobulinové izotypy krev   MeSH
• kohortové studie MeSH
• leukemická infiltrace MeSH
• lidé MeSH
• prognóza MeSH
• registrace MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• multicentrická studie MeSH
• práce podpořená grantem MeSH

The heterogeneity of common variable immunodeficiency (CVID) calls for a classification addressing pathogenic mechanisms as well as clinical relevance. This European multicenter trial was initiated to develop a consensus of 2 existing classification schemes based on flowcytometric B-cell phenotyping and the clinical course. The clinical evaluation of 303 patients with the established diagnosis of CVID demonstrated a significant coincidence of granulomatous disease, autoimmune cytopenia, and splenomegaly. Phenotyping of B-cell subpopulations confirmed a severe reduction of switched memory B cells in most of the patients that was associated with a higher risk for splenomegaly and granulomatous disease. An expansion of CD21(low) B cells marked patients with splenomegaly. Lymphadenopathy was significantly linked with transitional B-cell expansion. Based on these findings and pathogenic consideration of B-cell differentiation, we suggest an improved classification for CVID (EUROclass), separating patients with nearly absent B cells (less than 1%), severely reduced switched memory B cells (less than 2%), and expansion of transitional (more than 9%) or CD21(low) B cells (more than 10%). Whereas the first group contains all patients with severe defects of early B-cell differentiation, severely reduced switched memory B cells indicate a defective germinal center development as found in inducible constimulator (ICOS) or CD40L deficiency. The underlying defects of expanded transitional or CD21(low) B cells remain to be elucidated. This trial is re-gistered at http://www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html as UKF000308.

• MeSH
• B-lymfocyty imunologie   patologie   MeSH
• běžná variabilní imunodeficience * epidemiologie   imunologie   klasifikace   patologie   MeSH
• dospělí MeSH
• homeostáza imunologie   MeSH
• imunofenotypizace * MeSH
• imunoglobuliny krev   MeSH
• kohortové studie MeSH
• konsensus MeSH
• lidé středního věku MeSH
• lidé MeSH
• průtoková cytometrie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH