A case report of a 16 year old boy in whom selective IgA deficiency progressed to typical common variable immunodeficiency (CVID) is described. This boy with a history of frequent but not severe respiratory tract infections was referred to hospital because of severe pleuropneumonia and decreased levels of IgA (0.23 g/L), but normal IgG and IgM levels. Lymphocyte subpopulation determination revealed a decreased proportion of CD4+ lymphocytes (30%) and an increased proportion of CD8+ lymphocytes (32%), while CD3+, CD19+ and CD16+/56+ subpopulations were normal. During the subsequent 17 months a gradual decrease in IgG (ultimate level 2.23 g/L), IgA (< 0.05 g/L) and IgM (< 0.05 g/L) levels was observed, the decrease in IgM being the slowest reflecting a constant heavy chain gene order on chromosome 14. The observation supports the thesis of a close relation of selective IgA deficiency and common variable immunodeficiency.

• MeSH
• běžná variabilní imunodeficience krev   imunologie   terapie   MeSH
• deficience IgA krev   komplikace   imunologie   MeSH
• imunoglobulin G krev   imunologie   MeSH
• imunoglobulin M krev   imunologie   MeSH
• infekce dýchací soustavy etiologie   MeSH
• lidé MeSH
• mladiství MeSH
• pasivní imunizace MeSH
• progrese nemoci MeSH
• recidiva MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunoglobulin G MeSH
• imunoglobulin M MeSH

OBJECTIVE: To investigate the impact of growth hormone (GH) therapy in adults with childhood-onset GH deficiency on immune system. METHODS: Ten young GH deficient adults (7 males, age 19-28 years) were treated with recombinant human growth hormone for 6 months. The starting dose was 0.5 IU/m2/day (2 weeks), then it was doubled to 1.0 IU/m2/day. In 5/10 patients, the dose was further increased to 1.5 IU/m2/day at 4 weeks of therapy. Immunological studies were performed before treatment and after 6 weeks, 3 months and 6 months and included humoral (IgG, IgA, IgM, C3, C4 and immune complexes) and cellular parameters (total lymphocyte count and counts of CD3+, CD4+, CD8+ and CD19+ lymphocytes, the CD4+/CD8+ ratio and percentage of CD16+56+ and CD3+DR+). RESULTS: The cellular responses to GH therapy were subtle, but detectable, with the trend to the higher CD4+ and lower CD8+ lymphocytes and maximal changes at 6 months of therapy. They were reflected in CD4/CD8 ratio, which increased from 1.15 +/- 0.10 (mean +/- S.E.; baseline) to 1.37 +/- 0.11 (6 weeks; P < 0.05), 1.24 +/- 0.10 (3 months; n.s.) and to 1.59 +/- 0.20 (6 months; P < 0.05). The response in humoral immunity was characterized by a rapid decrease of circulating immunoglobulins (IgA: 1.40 +/- 0.25 g/l [mean+/-S.E.], baseline; 1.12 +/- 0.19, at 6 weeks; P < 0.05) and C4 (0.25 +/- 0.02 g/l, baseline; 0.19 +/- 0.01, at 6 weeks; P < 0.05) and a tendency to an increase in circulating immune complexes (29.1 +/- 8.1, baseline; 40.3 +/- 7.2, at 6 weeks; n.s.). These observations suggest a temporary immune complex formation after the onset of GH treatment which might play a partial role in developing oedema as a side effect of GH treatment, besides the known effect of GH on water retention. CONCLUSIONS: GH therapy in GH deficient young adults has a measurable effect on the increase of CD4/CD8 ratio and on the formation of immune complexes.

• MeSH
• dospělí MeSH
• hypofyzární nanismus farmakoterapie   imunologie   MeSH
• imunoglobuliny krev   MeSH
• imunokomplex krev   MeSH
• lidé MeSH
• počet lymfocytů MeSH
• poměr CD4 a CD8 lymfocytů MeSH
• růstový hormon terapeutické užití   MeSH
• tvorba protilátek MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• imunoglobuliny MeSH
• imunokomplex MeSH
• růstový hormon MeSH

Herpes simplex encephalitis is a rare complication of Herpes virus infections. Innate immune mechanisms are the first line of defence encountered by invading infectious agents. A 41-year-old man was admitted to the neurology department with the complaints of fever, headache, vertigo, tinnitus and ataxia. His first brain Magnetic Resonance Imagine showed nodular lesions in the medulla oblongata and the second showed a new left occipital lobe lesion in addition. In sera, Herpes Simplex Virus IgG and M values were positive and liver enzymes were found to be elevated. His diagnosis was Herpes encephalitis with liver involvement. CD19, CD20, CD21, CD22, CD35 receptors were found to be diminished. In this case we want to address that one of the causes of Wallenberg's lateral medullary syndrome can be Herpes simplex virus-1 and probable immune system deficiency can be researched.

• MeSH
• CD antigeny MeSH
• dospělí MeSH
• herpetická encefalitida komplikace   diagnóza   imunologie   MeSH
• laterální míšní syndrom etiologie   MeSH
• lidé MeSH
• lidský herpesvirus 1 * MeSH
• receptory imunologické nedostatek   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• CD antigeny MeSH
• receptory imunologické MeSH

Since late 2022, an increase in Streptococcus pyogenes (Group A Streptococcus, GAS) infections, both non-invasive and invasive (iGAS), has been reported globally. This study investigates iGAS cases complicated by recurrent infection (rGAS). From January to September 2023, four adults with severe iGAS suffered from rGAS. Clinical and whole-genome sequencing data were analysed. All patients required ICU admission and surgical debridement during their initial iGAS. The median interval between the initial iGAS and rGAS was 25.5 days, with a median duration of antibiotic treatment of 25 and 17.5 days, respectively. Patients A (female, age 69) and B (male, age 46) had upper limb necrotising fasciitis complicated by a subsequent cellulitis at the exact location. GAS emm1.3 (M1UK) was isolated in both patients, but patient A´s isolates carried a type-IV secretion system (T4SS), and this patient had a more severe course of infection. Patient C (male, age 66) had two episodes of bacteremia caused by GAS emm89.0 carrying T4SS and GAS emm12.37 with a frameshift in the rocA gene. Patient D (female, age 69) had upper limb cellulitis with bacteremia during the initial iGAS and upper limb cellulitis with septic gonitis as two concurrent manifestations of rGAS. All three isolates were identical, belonging to emm12.0 and carrying a 79 amino acid deletion in the SclA. Patients B and C had a reduced function of the complement lectin pathway and CD19+ lymphocyte deficiency. A combination of strain virulence factors and host immune deficiencies may predispose patients with iGAS to recurrence.

• Klíčová slova
• CD19+ deficiency, Streptococcus pyogenes, cellulitis, lectin pathway complement deficiency, necrotizing fasciitis, sepsis,
• MeSH
• antibakteriální látky terapeutické užití   MeSH
• bakteriemie mikrobiologie   MeSH
• dospělí MeSH
• fasciitida nekrotizující mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• recidiva MeSH
• sekreční systém typu IV genetika   MeSH
• sekvenování celého genomu MeSH
• senioři MeSH
• Streptococcus pyogenes * patogenita   genetika   imunologie   MeSH
• streptokokové infekce * imunologie   mikrobiologie   MeSH
• virulence MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antibakteriální látky MeSH
• sekreční systém typu IV 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

BACKGROUND: Agammaglobulinemia due to variants in IGLL1 has traditionally been considered an exceedingly rare form of severe B-cell deficiency, with only 8 documented cases in the literature. Surprisingly, the first agammaglobulinemic patient identified by newborn screening (NBS) through quantification of kappa-deleting recombination excision circles harbored variants in IGLL1. OBJECTIVE: We comprehensively reviewed clinical and immunologic findings of patients with B-cell deficiency attributed to variants in IGLL1. METHODS: NBS programs reporting the use of kappa-deleting recombination excision circle assays, the European Society for Immunodeficiencies Registry, and authors of published reports featuring patients with B-cell deficiency linked to IGLL1 variants were contacted. Only patients with (likely) pathogenic variants, reduced CD19+ counts, and no alternative diagnosis were included. RESULTS: The study included 13 patients identified through NBS, 2 clinically diagnosed patients, and 2 asymptomatic siblings. All had severely reduced CD19+ B cells (< 0.1 × 109/L) at first evaluation, yet subsequent follow-up assessments indicated residual immunoglobulin production. Specific antibody responses to vaccine antigens varied, with a predominant reduction observed during infancy. Clinical outcomes were favorable with IgG substitution. Two patients successfully discontinued substitution therapy without developing susceptibility to infections and while maintaining immunoglobulin levels. The pooled incidence of homozygous or compound heterozygous pathogenic IGLL1 variants identified by NBS in Austria, Czechia, and Switzerland was 1.3:100,000, almost double of X-linked agammaglobulinemia. CONCLUSION: B-cell deficiency resulting from IGLL1 variants appears to be more prevalent than initially believed. Despite markedly low B-cell counts, the clinical course in some patients may be milder than reported in the literature so far.

• Klíčová slova
• Agammaglobulinemia, B-cell deficiency, IGLL1, KREC, NBS, kappa-deleting recombination excision circles, lamba5, newborn screening, predominantly antibody deficiencies, vaccine response,
• MeSH
• agamaglobulinemie * genetika   imunologie   diagnóza   MeSH
• B-lymfocyty imunologie   MeSH
• dítě MeSH
• fenotyp * MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Complex perioperative immunodysfunction occurs in patients with renal cell carcinoma undergoing nephrectomy. Here, the effect of pretreatment with IL-2 is addressed. Of 63 patients who underwent tumour nephrectomy, 26 patients received four doses of 10 Mio IE/m2 IL-2 b.d. s.c. (i.e. a total of 40 Mio IE/m2) a week before operation, 37 did not. Parameters of cellular and humoral immunity (differential blood count, T-cell markers CD2, CD3, CD4, and CD8, B-cell markers CD19 and CD20, monocyte markers CD13 and CD14, NK-cell marker CD16, activation markers CD25, CD26, CD69 and HLA-DR, and cytokines IL-1-receptor antagonist (IL-1RA), IL-2, soluble IL-2-receptor (sIL-2R), IL-6, IL-10, and TGFbeta) were measured in peripheral venous blood. Blood was drawn before IL-2, one day before and immediately after the operation, and on the 1st, 3rd, 5th, and 10th postoperative day. All patients showed postoperatively elevated leukocyte and granulocyte counts, and elevated serum levels of cytokines IL-6 and IL-10. T-cell and activation markers were decreased. However, all these alterations were less accentuated in patients who had been pretreated with IL-2. Monocyte counts and IL-2 and TGFbeta levels were decreased, but IL-1RA and sIL-2R levels were elevated in pretreated patients. IL-2-related toxicity was WHO grade I-II in all patients, grade III in one patient. The anaesthetic regimen had no measurable effect. IL-6 concentrations were higher in renal venous than in venous pool blood, indicating IL-6 production in the tumour in vivo. Tumour-specific survival was better in pretreated patients with tumours extending beyond the kidney. Pretreatment with IL-2 modulates perioperative immunodysfunction in patients undergoing tumour nephrectomy. This affects in particular T-cell-mediated immunity and levels of cytokines IL-10 and IL-6. The IL-2 application scheme used here was followed by distinct counter regulation including monocytes, IL-2, sIL-2R, IL-1RA and TGFbeta. Taken together, pretreatment with IL-2 may complement surgery in the treatment of patients with renal cell carcinoma, and may help close the therapeutic gap between neo-adjuvant and adjuvant immunotherapy.

• MeSH
• antigeny povrchové krev   MeSH
• B-lymfocyty účinky léků   imunologie   MeSH
• biologické markery krev   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• interleukin-2 farmakologie   terapeutické užití   MeSH
• karcinom z renálních buněk komplikace   imunologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů farmakoterapie   imunologie   patofyziologie   MeSH
• míra přežití MeSH
• nádory ledvin komplikace   imunologie   chirurgie   MeSH
• nefrektomie škodlivé účinky   MeSH
• počet leukocytů MeSH
• předoperační péče metody   MeSH
• receptory cytokinové krev   MeSH
• senioři MeSH
• syndromy imunologické nedostatečnosti farmakoterapie   imunologie   prevence a kontrola   MeSH
• T-lymfocyty účinky léků   imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• antigeny povrchové MeSH
• biologické markery MeSH
• cytokiny MeSH
• interleukin-2 MeSH
• receptory cytokinové MeSH

Common variable immunodeficiency (CVID) refers to primary hypogammaglobulinemia with unknown pathogenesis. Although there is evidence for intrinsic B cell defects in some CVID patient groups, various abnormalities in cytokine production by T cells in CVID patients are frequently observed. Here, we demonstrate a relationship in the production of pro-inflammatory Th1 cytokines and regulatory B cells producing IL-10 between CVID patients and healthy controls. We describe CD19(+)CD24(hi)CD38(hi)IL-10(+) regulatory B cells generated after T cell stimulation of human peripheral blood lymphocytes ex vivo are able to suppress IFN-γ(+)TNF-α(+) producing CD4(+) T cells. This process is impaired in CVID patients, who present with both low numbers of CD19(+)CD24(hi)CD38(hi)IL-10(+) B cells and increased numbers of IFN-γ(+)TNF-α(+)CD4(+) T cells. Disruption of the regulatory B cell response to T cell stimulation explains the excessive T cell activation regarded as an immunoregulatory abnormality that is a frequent finding in CVID patients.

• Klíčová slova
• B cell, Common variable immunodeficiency (CVID), Cytokine production, Flow cytometry, T cell,
• MeSH
• aktivace lymfocytů MeSH
• běžná variabilní imunodeficience imunologie   MeSH
• buněčná diferenciace imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   metabolismus   MeSH
• cytokiny imunologie   metabolismus   MeSH
• dospělí MeSH
• interferon gama imunologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• průtoková cytometrie MeSH
• regulační B-lymfocyty imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• T-lymfocyty imunologie   metabolismus   MeSH
• TNF-alfa imunologie   metabolismus   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
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• interferon gama MeSH
• TNF-alfa MeSH

Hypogammaglobulinemia (serum IgG lower than 2 SD below the age-matched mean) and clinical symptoms such as increased susceptibility to infection, autoimmune manifestations, granulomatous disease, and unexplained polyclonal lymphoproliferation are considered to be diagnostic hallmarks in patients with common variable immunodeficiency (CVID), the most frequent clinically severe primary immunodeficiency syndrome. In the present study, we investigated patients with hypogammaglobulinemia and no clinical or immunological signs of defective cell-mediated immunity and differentiated two groups on the basis of their IgG antibody formation capacity against a variety of different antigens (bacterial toxins, polysaccharide antigens, viral antigens). Patients with hypogammaglobulinemia and intact antibody production (HIAP) displayed no or only mild susceptibility to infections, while CVID patients showed marked susceptibility to bacterial infections that normalized following initiation of IVIG or subcutaneous immunoglobulin replacement therapy. There was a substantial overlap in IgG serum levels between the asymptomatic HIAP group and the CVID patients examined before immunoglobulin treatment. HIAP patients showed normal levels of switched B-memory cells (CD19(+)CD27(+)IgD(-)), while both decreased and normal levels of switched B-memory cells could be found in CVID patients. IgG antibody response to a primary antigen, tick-borne encephalitis virus (TBEV), was defective in CVID patients, thus confirming their substantial defect in IgG antibody production. Defective IgG antibody production against multiple antigens could also be demonstrated in an adult patient with recurrent infections but normal IgG levels. To facilitate early treatment before recurrent infections may lead to organ damage, the antibody formation capacity should be examined in hypogammaglobulinemic patients and the decision to treat should be based on the finding of impaired IgG antibody production.

• Klíčová slova
• CVID, IVIG, IgG antibody deficiency, hypogammaglobulinemia, immunoglobulin treatment, primary vaccination,
• Publikační typ
• časopisecké články MeSH

Common variable immunodeficiency (CVID) is primary hypogammaglobulinaemia with an unknown aetiopathogenesis. Although various abnormalities of T and B cells have been described, their pathogenetic roles are unclear. We determined T and B lymphocyte subsets known to be abnormal in CVID in order to disclose possible relations between numerical abnormalities in those cells. Markers associated with B cell development (CD21, CD27, IgM, IgD) were determined on B lymphocytes (CD19+); T lymphocyte development (CD45RA, CD45RO, CD62L) and activation markers (CD25, CD27, CD28, CD29, CD38, CD57, HLA-DR) were determined on CD4+ and CD8+ T lymphocytes in 42 CVID patients and in 33 healthy controls. Abnormalities in CD4+ T lymphocyte activation markers (increase in CD29, HLA-DR, CD45RO, decrease in CD27, CD62L, CD45RA) were observed particularly in patients with a decreased number of memory (CD27+) and mature (CD21+) B cells (group Ia according to the Freiburg group's classification), while abnormalities observed in CD8+ cells (increase in CD27 and CD28 and decrease in HLA-DR, CD57 and CD38) did not depend upon grouping patients together according to B lymphocyte developmental subpopulations. We observed correlations between immature B cells (IgM+ CD21-) and expression of CD27, CD62L, CD45RA, CD45RO and HLA-DR on CD4+ T cells in CVID patients but not in the control group. The expression of CD27 and CD45RA on CD4+ T lymphocytes, such as the percentage of IgD+ CD27- and IgD+ CD27+ cells in B lymphocytes, showed age dependency to be more significant than in the control group. Our study demonstrates that T and B lymphocyte abnormalities in CVID are partially related to each other. Some of those abnormalities are not definite, but may evolve with age of the patient.

• MeSH
• aktivace lymfocytů imunologie   MeSH
• antigeny diferenciační B-lymfocytární imunologie   MeSH
• B-lymfocyty imunologie   MeSH
• běžná variabilní imunodeficience klasifikace   imunologie   MeSH
• biologické markery analýza   MeSH
• CD antigeny imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• diferenciační antigeny T-lymfocytů imunologie   MeSH
• dospělí MeSH
• imunoglobulin D imunologie   MeSH
• imunoglobulin M imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• podskupiny B-lymfocytů imunologie   MeSH
• průtoková cytometrie metody   MeSH
• stárnutí imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny diferenciační B-lymfocytární MeSH
• biologické markery MeSH
• CD antigeny MeSH
• diferenciační antigeny T-lymfocytů MeSH
• imunoglobulin D MeSH
• imunoglobulin M MeSH