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.

• Klíčová slova
• CVID, Chest CT, bronchial pathology, bronchiectasis, primary antibody deficiency,
• 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

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
• Názvy látek
• DNA virů 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 κ 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 klasifikace   imunologie   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
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CD24 MeSH
• CD24 protein, human MeSH Prohlížeč

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
• histokompatibilita - antigeny třídy I genetika   MeSH
• imunoglobulin G krev   MeSH
• intravenózní imunoglobuliny krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   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
• Názvy látek
• Fc receptor, neonatal MeSH Prohlížeč
• histokompatibilita - antigeny třídy I MeSH
• imunoglobulin G MeSH
• intravenózní imunoglobuliny MeSH
• messenger RNA MeSH
• receptory Fc MeSH

Common variable immunodeficiency (CVID) is the most frequent clinically manifested primary immunodeficiency. According to clinical and laboratory findings, CVID is a heterogeneous group of diseases. Recently, the defects of molecules regulating activation and terminal differentiation of B lymphocytes have been described in some patients with CVID. In this study, we show the overview of deficiencies of inducible costimulator, transmembrane activator and calcium-modulator and cytophilin ligand interactor, CD19 molecules, their genetic basis, pathogenesis and clinical manifestations.

• MeSH
• běžná variabilní imunodeficience genetika   imunologie   patologie   MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Common variable immunodeficiency (CVID) comprises a heterogeneous group of patients with as yet undefined genetic defects. Patients with CVID have in common a decrease in the levels of one or more serum immunoglobulin isotypes and a severe defect in the production of specific antibodies. Typically, the patients suffer from recurrent infections of the upper and lower respiratory tract or the gastrointestinal tract. In consequence of these infections patients may develop severe organ damage, such as chronic pulmonary disease with bronchiectases, leading to pulmonary failure. Early diagnosis of CVID is important, as antibody deficiency can efficiently be treated by regular intravenous IgG (IVIG) substitution therapy. IVIG therapy prevents the occurrence of further acute infectious episodes and the development of long-term complications. The basic immunological defect(s) in patients with CVID are still unknown. There is currently no convincing evidence for an intrinsic B-cell defect in patients with CVID. A defect in T-cell activation due to impaired signal transduction upon T-cell receptor triggering has been described in a large subgroup of patients with CVID. Defective T-cell activation may lead to an impairment in cognate T-B-cell interaction due to impaired expression of CD40 ligand and/or abnormalities in the production T-cell-derived cytokines required for fully functional B-cell activation, proliferation and/or differentiation which could indeed explain the impairment in antibody production present in CVID patients.

• MeSH
• aktivace lymfocytů MeSH
• běžná variabilní imunodeficience diagnóza   imunologie   patologie   terapie   MeSH
• diferenciální diagnóza MeSH
• infekce etiologie   MeSH
• intravenózní imunoglobuliny terapeutické užití   MeSH
• lidé MeSH
• ligand CD40 MeSH
• membránové glykoproteiny imunologie   MeSH
• novorozenec MeSH
• receptory antigenů T-buněk nedostatek   MeSH
• signální transdukce MeSH
• spolupráce lymfocytů MeSH
• T-lymfocyty imunologie   patologie   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• intravenózní imunoglobuliny MeSH
• ligand CD40 MeSH
• membránové glykoproteiny MeSH
• receptory antigenů T-buněk MeSH