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Eibl M.M.,Immunology Outpatient Clinic
Immunotherapy | Year: 2012

Evaluation of: Cortes JE, Curns AT, Tate JE et al. Rotavirus vaccine and health care utilization for diarrhea in U.S. children. N. Engl. J. Med. 365(12), 1108-1117 (2011). Cortes et al. thoroughly analyzed the effect of the introduction of mass rotavirus vaccination on healthcare utilization in a population of approximately 2 million US children under 5 years of age. According to the results of the study, hospitalization has been reduced from prevaccination periods by 89% for rotavirus diarrhea and by 44% for diarrheal disease. The estimated reduction of hospitalizations during the two (single-year) periods amounted to 64,855 and the respective savings in treatment costs were US 278 million. The significance of this paper is its approach to the estimation of vaccine efficacy by the assessment of vaccination coverage and hospitalization, as well as emergency department and outpatient visits in a large population of children without any 'selection' (e.g., hospitalization) bias. © 2012 Future Medicine Ltd.


Eibl M.M.,Immunology Outpatient Clinic | Wolf H.M.,Immunology Outpatient Clinic
Immunotherapy | Year: 2015

Vaccination has been an important healthcare measure in preventing infectious diseases. The response to vaccination is reduced in immunocompromised patients, primary immune deficiency (PID) and secondary immune deficiency (SID), but vaccination studies still demonstrated a protective effect resulting in reducing complications, hospitalization, treatment costs and even mortality. The primary physician and the specialist directing patient care are responsible for vaccination. Live vaccines are contraindicated in patients with severe immune impairment, killed vaccines are highly recommended in PID and SID. Criteria have been defined to distinguish high-or low-level immune impairment in the different disease entities among PID and SID patients. For patients who do not respond to diagnostic vaccination as characterized by antibody failure immunoglobulin replacement is the mainstay of therapy. © 2015 Martha M Eibl and Hermann M Wolf.


Fischer M.B.,Medical University of Vienna | Fischer M.B.,Danube University Krems | Wolfram W.,Medical University of Vienna | Binder C.J.,Medical University of Vienna | And 4 more authors.
Frontiers in Immunology | Year: 2015

Background: Common variable immunodeficiency (CVID) is the most common clinically severe primary immunodeficiency and comprises a heterogeneous group of patients with recurrent severe bacterial infections due to the failure to produce IgG antibodies after exposure to infectious agents and immunization. Diagnostic recommendations for antibody failure include assessment of isoagglutinins. We have readdressed this four decades old but still accepted recommendation with up to date methodology. Methods: Anti-A/B IgM- and IgG-antibodies were measured by Diamed-ID Micro Typing, surface plasmon resonance (SPR) using the Biacore® device and flow cytometry. Results: When Diamed-ID Micro Typing was used, CVID patients (n = 34) showed IgG- and IgM-isoagglutinins that were comparable to healthy volunteers (n = 28), while all XLA patients (n = 8) had none. Anti-A/B IgM-antibodies were present in more than 2/3 of the CVID patients and showed binding kinetics comparable to anti-A/B IgM-antibodies from healthy individuals. A correlation could be found in CVID patients between levels of anti-A/B IgM-antibodies and levels of serum IgM and PnP-IgM-antibodies. In contrast in CVID patients as a group ABO antibodies were significantly decreased when assessed by SPR, which correlated with levels of switched memory, non-switched memory and naïve B cells, but all CVID patients had low/undetectable anti-A/B IgG-antibodies. Conclusion: These results indicate that conventional isoagglutinin assessment and assessment of anti-A/B IgM antibodies are not suited for the diagnosis of impaired antibody production in CVID. Examination of anti-A/B IgG antibodies by SPR provides a useful method for the diagnosis of IgG antibody failure in all CVID patients studied, thus indicating an important additional rationale to start immunoglobulin replacement therapy early in these patients, before post-infectious sequelae develop. © 2015 Fischer, Wolfram, Binder, Böhmig, Wahrmann, Eibl and Wolf.


Wolf H.M.,Immunology Outpatient Clinic | Thon V.,Masaryk University | Thon V.,St Annes University Hospital | Litzman J.,Masaryk University | And 2 more authors.
Frontiers in Immunology | Year: 2015

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. © 2015 Wolf, Thon, Litzman and Eibl.


PubMed | Danube University Krems, Immunology Outpatient Clinic and Medical University of Vienna
Type: | Journal: Frontiers in immunology | Year: 2015

Common variable immunodeficiency (CVID) is the most common clinically severe primary immunodeficiency and comprises a heterogeneous group of patients with recurrent severe bacterial infections due to the failure to produce IgG antibodies after exposure to infectious agents and immunization. Diagnostic recommendations for antibody failure include assessment of isoagglutinins. We have readdressed this four decades old but still accepted recommendation with up to date methodology.Anti-A/B IgM- and IgG-antibodies were measured by Diamed-ID Micro Typing, surface plasmon resonance (SPR) using the Biacore() device and flow cytometry.When Diamed-ID Micro Typing was used, CVID patients (n=34) showed IgG- and IgM-isoagglutinins that were comparable to healthy volunteers (n=28), while all XLA patients (n=8) had none. Anti-A/B IgM-antibodies were present in more than 2/3 of the CVID patients and showed binding kinetics comparable to anti-A/B IgM-antibodies from healthy individuals. A correlation could be found in CVID patients between levels of anti-A/B IgM-antibodies and levels of serum IgM and PnP-IgM-antibodies. In contrast in CVID patients as a group ABO antibodies were significantly decreased when assessed by SPR, which correlated with levels of switched memory, non-switched memory and nave B cells, but all CVID patients had low/undetectable anti-A/B IgG-antibodies.These results indicate that conventional isoagglutinin assessment and assessment of anti-A/B IgM antibodies are not suited for the diagnosis of impaired antibody production in CVID. Examination of anti-A/B IgG antibodies by SPR provides a useful method for the diagnosis of IgG antibody failure in all CVID patients studied, thus indicating an important additional rationale to start immunoglobulin replacement therapy early in these patients, before post-infectious sequelae develop.


Stollberger C.,Krankenanstalt Rudolfstiftung | Krutisch G.,Krankenanstalt Rudolfstiftung | Finsterer J.,Krankenanstalt Rudolfstiftung | Wolf H.M.,Immunology Outpatient Clinic
Blood Coagulation and Fibrinolysis | Year: 2014

Epistaxis resulted in severe anemia in an 89-year-old Caucasian woman under a therapy with dabigatran for 12 months because of atrial fibrillation. Correction of the anemia was difficult because it was impossible to assess her blood group due to polyagglutination. Since hospital records disclosed that in 2011, her blood group was O positive, acquired polyagglutination was assumed. After 66 days, it was again possible to assess the blood group as O positive. Immunologic investigations disclosed that antinuclear antibodies and antihistone antibodies were elevated, and antibodies to double-stranded DNA were negative. Drug-induced lupus was diagnosed due to the autoantibody profile detected. Copyright © Lippincott Williams & Wilkins.


PubMed | Immunology Outpatient Clinic
Type: Journal Article | Journal: Immunotherapy | Year: 2015

Vaccination has been an important healthcare measure in preventing infectious diseases. The response to vaccination is reduced in immunocompromised patients, primary immune deficiency (PID) and secondary immune deficiency (SID), but vaccination studies still demonstrated a protective effect resulting in reducing complications, hospitalization, treatment costs and even mortality. The primary physician and the specialist directing patient care are responsible for vaccination. Live vaccines are contraindicated in patients with severe immune impairment, killed vaccines are highly recommended in PID and SID. Criteria have been defined to distinguish high- or low-level immune impairment in the different disease entities among PID and SID patients. For patients who do not respond to diagnostic vaccination as characterized by antibody failure immunoglobulin replacement is the mainstay of therapy.


PubMed | Biomedizinische ForschungsgmbH and Immunology Outpatient Clinic
Type: | Journal: BMC microbiology | Year: 2016

Nosocomial infections caused by the bacterial pathogen Staphylococcus aureus can lead to serious complications due to the varying presence of secreted toxins. Comparative studies of genomic information and production rates are needed to assess the pathogenic potential of isolated strains. Genotypic and phenotypic profiling of clinical and colonising isolates of S. aureus was used to characterise the release of exotoxins. Blood isolates were compared with colonisation strains to determine similarities and differences of single strains and clusters.Fifty-one fresh isolates obtained from colonised individuals (n=29) and S. aureus bacteremia (SAB) patients (n=22) were investigated. The prevalence of genes encoding for three cytolysins (alpha/beta/gamma toxin) and twenty-four superantigens (SEA-SElX) was determined. Isolates exhibited eighteen distinct combinations of superantigens. Sequence analysis identified mutated open reading frames in hla in 13.7% of all strains, in selw (92.2%) and in selx (15.7%). All corrupted genes were associated with specific clonal complexes. Functional assessment of alpha toxin activity by a rabbit erythrocyte lysis assay revealed that supernatants lacking alpha toxin still displayed hemolysis. This was due to the presence of gamma toxin, as proven by inhibition experiments using antisera raised against the respective recombinant proteins. Alpha toxin, SEC, and TSST1 production was quantified by enzyme-linked immunosorbent assays on supernatants of all hla, sec, and tst positive isolates. Blood isolates and colonising strains showed comparable amounts of secreted proteins within a wide range. Agr types I to IV were identified, but did not allow a prediction of high or low production rates. In contrast, alpha toxin production rates between distinct clonal complexes clearly differed. Spa typing was performed and revealed thirty-two unique spa gene patterns and eight small clusters comprising nineteen isolates. Recognised spa-typing clusters displayed highly similar production rates.Production rates of the three most prevalent exotoxins varied within both groups of blood isolates and colonising strains. By comparing genotypes and secretion, we found that identical complex gene patterns did not allow predictions of toxin production and function. However, identification of spa typing clusters was suitable to predict similar quantities of released exotoxins.


PubMed | Masaryk University and Immunology Outpatient Clinic
Type: | Journal: Frontiers in immunology | Year: 2015

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.


PubMed | Danube University Krems, Immunology Outpatient Clinic, Sigmund Freud Private University Vienna, Rudolfstiftung Hospital of the City of Vienna and Medical University of Vienna
Type: | Journal: Frontiers in immunology | Year: 2016

Blood group antibodies are natural antibodies that develop early in life in response to cross-reactive environmental antigens in the absence of antigen encounter. Even later in life structural similarities in saccharide composition between environmental antigens such as bacterial polysaccharides and blood group A/B antigens could lead to changes in serum levels, IgM/IgG isotype, and affinity maturation of blood group anti-A/B antibodies. We addressed the question whether immunization with pneumococcal polysaccharide (PnP) vaccine Pneumo 23 Vaccine Pasteur Merieux (Pn23) could have such an effect in patients with type I diabetes mellitus (DM I), an autoimmune disease where an aberrant immune response to microbial antigens likely plays a role.Anti-PnP IgM and IgG responses were determined by ELISA, and the DiaMed-ID Micro Typing System was used to screen anti-A/B antibody titer before and after Pn23 immunization in 28 healthy individuals and 16 patients with DM I. In addition, surface plasmon resonance (SPR) technology using the BiacoreAll healthy individuals and DM I patients responded with anti-PnP IgM and IgG antibody production 4-6weeks after Pn23 immunization, while no increase in blood group anti-A/B antibody titer was observed when measured by the DiaMed-ID Micro Typing System. Interestingly, isotype-specific testing by SPR technology revealed an increase in blood group anti-A/B IgG, but not IgM, following Pn23 immunization in both patients and controls. No change in binding characteristics of blood group anti-A/B antibodies could be detected following Pn23 vaccination, supporting the assumption of an increase in IgG antibody titer with no or very little affinity maturation.The study provides evidence for epitope sharing between pneumococcal polysaccharides and blood group ABO antigens, which leads to a booster of blood group anti-A/B antibodies of the IgG isotype after Pn23 immunization in healthy individuals. Manifest autoimmunity such as present in DM I patients has no additional effect on the cross-reactive antibody response against pneumococcal polysaccharides and blood group antigens.

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