Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunoglobulin-producing cells in mucosal tissues, quantitatively the body's most important humoral immune system, synthesize mainly dimers and larger polymers of IgA (poly-IgA) with incorporated J (joining) chain. Poly-IgA is actively transported to exocrine secretions by a transmembrane epithelial glycoprotein called secretory component. Enhancing secretory immunity by oral vaccination is an interesting possibility, but mucosal antigen uptake and local immune regulation are complex and only partly understood. Immunoglobulin isotype response patterns in the upper respiratory mucosa and distal gut are strikingly different. The preferential production of IgA1 in nasal and bronchial mucosae is intriguing in view of the frequent synthesis of IgA1-specific proteases by Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. A relationship of proneness to produce invasive disease and enzymatically induced deterioration of secretory immunity has been proposed. Differences in mucosal immune response patterns among patients with selective IgA deficiency or IgG subclass deficiencies also suggest that local humoral immunity is an important variable in resistance to infections.
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PMID:Humoral immune response patterns of human mucosae: induction and relation to bacterial respiratory tract infections. 158 57

The antibody response to the capsular polysaccharide of Haemophilus influenzae type b was evaluated after vaccination with the capsular polysaccharide or its tetanus toxoid conjugate in 41 randomized patients with recurrent infections, IgA deficiency, common variable immunodeficiency, or the Wiskott-Aldrich syndrome. Serum antibodies were measured using a Farr assay for total antibodies and an enzyme-linked immunosorbent assay for antibodies of the three main immunoglobulin classes and of each IgG subclass. Antibody levels reached concentrations generally considered as protective in the majority of cases, the best response being observed after two injections of the conjugate vaccine with a 1-month interval. Vaccination with the conjugate therefore seems to be promising for the prevention of Haemophilus influenzae type b infections in such patients.
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PMID:Immunogenicity of Haemophilus influenzae type b capsular polysaccharide and its tetanus toxoid conjugate in patients with recurrent infections or humoral immunodeficiency. 159 74

Primary B-cell immunodeficiency is relatively frequent and may result in recurrent bacterial infections involving notably the respiratory tract, and in chronic severe enteroviral infections in patients with agammaglobulinaemia. Selective IgG2 isotype deficiency results in pneumococcal, Haemophilus influenzae and pseudomonal infections, since it is associated with defective production of antibodies that are specifically directed against bacterial capsular polysaccharides. Progress has recently been achieved in the determination of genetic and molecular bases of some of these immunodeficiencies. In X-linked agammaglobulinaemia, the abnormal gene has been located on the long arm of the X chromosome (Xq22-23); the intrinsic B-cell abnormality blocks differentiation at the pre-B stage, before the genes coding for light chain immunoglobulins are rearranged. There is now a strong suspicion that IgA deficiency, hypoglobulinaemia with variable expression and some selective IgG isotype deficiencies are three ways of expressing one single abnormality a genetic factor of which is located in the class III region of the HLA complex and perhaps also associated with HLA class II DQ. Treatment of deficient IgG production with intravenous immunoglobulin has thoroughly altered the prognosis of these diseases. Complete IgA deficiency carries a risk of accident by production of anti-IgA antibodies, which means that patients with isolated IgA deficiency should not be treated, that these antibodies should systematically be looked for in patients with IgA deficiency associated with partial deficiency of other immunoglobulins, and that these patients should be treated with IgA-free immunoglobulin preparations.
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PMID:[Primary immune deficiencies of B-lymphocytes]. 204 14

Thirty-one of 75 patients with recurrent upper respiratory infections were found to have immunoglobulin G subclass deficiencies with normal levels of total immunoglobulin G in a clinical allergy and asthma practice. Sixteen were IgG3 deficient, thirteen IgG2 deficient, and two were IgG1 deficient. Only one patient had an IgA deficiency. Two patients have normal IgG with decreased PRP titers. Serum antibody titers to the capsular polysaccharide of Haemophilus influenzae type B (HibCP) were found to be low in seven patients. Other investigators have established relationships between these deficiencies and recurrent infections. When investigating patients with recurrent infections, it seems prudent to look beyond simple quantitative immunoglobulins.
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PMID:IgG subtype abnormalities with normal total IgG in a clinical allergy practice. 349 Jan 98

Serum immunoglobulins and IgG subclasses were measured in 30 children with recurrent infections. Seven patients had low IgG2 concentrations (less than 3SD below the geometric mean for age). Four of these seven patients had normal concentrations of IgG, IgA and IgM, and thus would have been considered immunologically normal by routine criteria. The seven children with IgG2 deficiency had more severe infections than the 23 children with normal IgG2. Five children had recurrent pneumonia or sinusitis, one had recurrent invasive Haemophilus influenzae type b infections, and one had severe pneumococcal meningitis. Their immunologic abnormalities were heterogeneous. Two children had isolated IgG2 deficiency, two had IgG2-IgG4 deficiency, one had IgG2-IgG4-IgA deficiency, one had IgG2-IgA deficiency, and one had severe IgG1-IgG2 deficiency with abnormal T cell function and thrombocytopenia. Thus IgG2 deficiency occurs frequently among children with recurrent infections, and is associated with a variety of clinical and immunologic abnormalities.
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PMID:Spectrum of IgG2 subclass deficiency in children with recurrent infections: prospective study. 370 8

We studied 20 children with recurrent sinopulmonary infections and serum IgG levels within the normal range, who had selective IgG-subclass deficiency. Twelve of the children were IgG2 deficient, five were IgG3 deficient, and three were deficient in both IgG2 and IgG3. IgA deficiency was present in 3 of the 20 patients. In the children with IgG2 deficiency, serum antibody concentrations to the capsular polysaccharide of Hemophilus influenzae type B (Hib) were significantly lower than those in age-matched controls, both before and after immunization with the Hib capsular polysaccharide antigen, which elicits antibody predominantly of the IgG2 subclass. In contrast, their serum antibody titers to the tetanus and diphtheria toxoid protein antigens, which elicit antibody predominantly of the IgG1 subclass, were normal in comparison with those of age-matched controls. These results suggest that impairment of the antibody response to specific microbial antigens predisposes patients with selective IgG-subclass deficiencies to recurrent infections. Thus, as an aid in determining therapy, children with recurrent infections and normal total serum IgG should be evaluated for this condition.
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PMID:Recurrent sinopulmonary infection and impaired antibody response to bacterial capsular polysaccharide antigen in children with selective IgG-subclass deficiency. 387 40

In order to define abnormalities of humoral immunity which determine susceptibility to respiratory tract infections in IgA-deficient adults, serum IgG subclass concentrations, and serum concentrations of pneumococcal antibodies and Haemophilus influenzae type B (Hib) antibodies sera from IgA-deficient adults with and without susceptibility to respiratory tract infections were compared. Infection susceptibility was not related to the degree of IgA deficiency, but was related to deficiency of IgG4 and, to a lesser extent, IgG2, as well as to low basal serum concentrations of pneumococcal polysaccharide antibodies. The combination of IgG2 and/or IgG4 deficiency and a non-protective basal serum concentration of antibody against two or more pneumococcal polysaccharides was present in the serum of six of 12 (50%) patients with severe infections, but only one of 44 (2%) patients without infections. Furthermore, the preservation of antibody responses against the most immunogenic pneumococcal polysaccharide type 3, but not against the less immunogenic types 7F, 9N and 14, in patients with severe infections suggested that abnormalities of pneumococcal polysaccharide antibody responses might include defects of affinity maturation.
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PMID:Severity of infections in IgA deficiency: correlation with decreased serum antibodies to pneumococcal polysaccharides and decreased serum IgG2 and/or IgG4. 769 22

The respiratory mucosa is protected primarily by a secretory immune system that is under complex and only partly understood immunoregulatory control. Secretory immunoglobulins (SIgA and SIgM) protect the mucosal surface by immune exclusion of antigens. However, the fact that most IgA produced in the respiratory tract belongs to the IgA1 subclass renders SIgA in this region susceptible to IgA-specific proteases produced by Haemophilus influenzae, Streptococcus pneumonia, and Neisseria meningitidis. Immunoglobulin G can also perform immune exclusion at respiratory surfaces but, like IgE, it reaches the secretions merely by passive diffusion. The phlogistic properties of antibodies belonging to these classes explain their potential involvement in maintaining mucosal inflammation. In patients with selective IgA deficiency, SIgA is lacking and is not regularly compensated for satisfactorily by SIgM. In such patients unexplained immunoregulatory mechanisms, perhaps involving the local microbiota, give rise to a large number of IgD-producing cells in the upper respiratory tract. Immunoglobulin D cannot act as a secretory antibody and might block the protective properties of IgG; this could explain why these patients are particularly prone to recurrent infections. Our observations show that there are large individual variations in the mucosal immune system with regard to humoral immunity in the upper respiratory tract.
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PMID:The role of humoral mucosal immunity in the induction and maintenance of chronic airway infections. 776 61

A total of 117 consecutive patients with primary antibody deficiencies were followed for up to 5 years with regard to acute respiratory tract infections. Nontypeable Haemophilus influenzae (NTHI) was the sole pathogen in 61% (202/330) of the samples from which a potential pathogen was recovered. Common variable immunodeficiency (CVI) was the most prevalent condition (27/39 patients) in the group where H. influenzae was isolated. In patients where H. influenzae was not found only 9/78 patients had CVI. 49 of these 78 patients had isolated IgG3 or IgA deficiency. Both of these entities seemed to be associated with a lower prevalence of NTHI infections. 13 of 18 patients with at least 2 isolates of NTHI were colonized with the same strain from 3 to 43 months as shown by total genomic DNA-fingerprinting. Recurrent symptomatic infections occurred in these patients despite substitution therapy with gammaglobulins and repeated antibiotic treatments. All but 2 of the 224 H. influenzae isolates were beta-lactamase negative and sensitive to ampicillin. The use of 10 lipopolysaccharide-specific monoclonal antibodies in a whole cell ELISA showed that the LPS-epitopes on the 224 H. influenzae isolates from the hypogammaglobulinemic group were very similar to 499 NTHI isolates from immunocompetent patients with respiratory infections. One may therefore conclude that i) patients with CVI, were prone to be permanently colonized with NTHI, and ii) the colonizing bacteria were ordinary strains showing the same LPS-phenotypes as those strains that cause acute respiratory tract infections in immunocompetent individuals.
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PMID:Characterization of Haemophilus influenzae isolates from the respiratory tract of patients with primary antibody deficiencies: evidence for persistent colonizations. 865 61

IgA1 protease activity, which allows bacteria to cleave human IgA1 in the hinge region, represents a striking example of convergent evolution of a specific property in bacteria. Although it has been known since 1979 that IgA1 protease is produced by the three leading causes of bacterial meningitis in addition to important urogenital pathogens and some members of the oropharyngeal flora, the exact role of this enzyme in bacterial pathogenesis is still incompletely understood owing to lack of a satisfactory animal model. Cleavage of IgA1 by these post-proline endopeptidases efficiently separates the monomeric antigen-binding fragments from the secondary effector functions of the IgA1 antibody molecule. Several in vivo and in vitro observations indicate that the enzymes are important for the ability of bacteria to colonize mucosal membranes in the presence of S-IgA antibodies. Furthermore, the extensive cleavage of IgA sometimes observed in vivo, suggests that IgA1 protease activity results in a local functional IgA deficiency that may facilitate colonization of other microorganisms and the penetration of potential allergens. It has been hypothesized that IgA1 protease activity of Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae, under special immunological circumstances, allows these bacteria to take advantage of specific IgA1 antibodies in a strategy to evade other immune factors of the human body. The decisive factor is the balance between IgA antibodies against surface antigens of the respective bacteria and their IgA1 protease. Recent studies have shown that serine-type IgA1 proteases of H. influenzae, meningococci, and gonococci belong to a family of proteins used by a diverse group of Gram-negative bacteria for colonization and invasion.
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PMID:Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence. 870 38


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