1/9. autoantibodies to interferon-gamma in a patient with selective susceptibility to mycobacterial infection and organ-specific autoimmunity.We evaluated a patient with disseminated mycobacterium tuberculosis and mycobacterium chelonae infection, of which he died. He also developed autoimmune (type I) diabetes and primary hypothyroidism. His serum contained a high titer of immunoglobulin g autoantibody to interferon-gamma (IFN-gamma) capable of blocking in vitro responses to this cytokine by peripheral blood mononuclear cells from normal donors. These results suggest that autoantibodies to IFN-gamma can induce susceptibility to disseminated mycobacterial infection, which may be refractory to chemotherapy.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
2/9. Acquired predisposition to mycobacterial disease due to autoantibodies to IFN-gamma.Genetic defects in the IFN-gamma response pathway cause unique susceptibility to intracellular pathogens, particularly mycobacteria, but are rare and do not explain mycobacterial disease in the majority of affected patients. We postulated that acquired defects in macrophage activation by IFN-gamma may cause a similar immunological phenotype and thus explain the occurrence of disseminated intracellular infections in some patients without identifiable immune deficiency. macrophage activation in response to IFN-gamma and IFN-gamma production were studied in whole blood and PBMCs of 3 patients with severe, unexplained nontuberculous mycobacterial infection. In all 3 patients, IFN-gamma was undetectable following mitogen stimulation of whole blood, but significant quantities were detectable in the supernatants of PBMCs when stimulated in the absence of the patients' own plasma. The patients' plasma inhibited the ability of IFN-gamma to increase production of TNF-alpha by both autologous and normal donor PBMCs, and recovery of exogenous IFN-gamma from the patients' plasma was greatly reduced. Using affinity chromatography, surface-enhanced laser desorption/ionization mass spectrometry, and sequencing, we isolated an IFN-gamma-neutralizing factor from the patients' plasma and showed it to be an autoantibody against IFN-gamma. The purified anti-IFN-gamma antibody was shown to be functional first in blocking the upregulation of TNF-alpha production in response to endotoxin; second in blocking induction of IFN-gamma-inducible genes (according to results of high-density cDNA microarrays); and third in inhibiting upregulation of HLA class II expression on PBMCs. Acquired defects in the IFN-gamma pathway may explain unusual susceptibility to intracellular pathogens in other patients without underlying, genetically determined immunological defects.- - - - - - - - - - ranking = 0.2keywords = bacterial infection (Clic here for more details about this article) |
3/9. Overwhelming pneumococcal bacteraemia in systemic lupus erythematosus.An 18 year old woman presented with fulminant pneumococcal bacteraemia and subsequently died with multisystem organ failure. A search for diseases predisposing to overwhelming encapsulated bacterial infections was negative except for previously undiagnosed systemic lupus erythematosus (SLE). This case emphasises the severity of immune system dysfunction in some patients with SLE, regardless of immunosuppressive treatment. The possible relation between Fc receptor dysfunction and pneumococcal bacteraemia in SLE is discussed.- - - - - - - - - - ranking = 0.2keywords = bacterial infection (Clic here for more details about this article) |
4/9. Susceptibility to infections in children with selective IgA- and IgA-IgG subclass deficiency.This study included 36 children with IgA-deficiency, increased susceptibility to infections and/or other disorders. Recurrent, usually bacterial infections were noticed in 23 out of 26 patients (88%) with complete and in 7 out of 10 patients (70%) with partial IgA-deficiency. All patients with severe infections had complete IgA-deficiency. Complete IgA-deficiency was also present in the six children who had autoimmune disorders associated with recurrent infections. In 22 out of the 36 patients studied the serum could be analysed for concomitant IgG subclass deficiencies: one patient had marked decrease of IgG2. In a second patient IgG4 was not detectable. Two patients had combined IgG2-IgG4-deficiency. In a girl with severe acute and chronic infections and relapsing idiopathic thrombocytopenic purpura, IgA-IgG2-IgG4-deficiency was found to be the prodromal stage of common variable immunodeficiency with panhypogammaglobulinaemia.- - - - - - - - - - ranking = 0.2keywords = bacterial infection (Clic here for more details about this article) |
5/9. actinomycosis meningitis in a girl with incontinentia pigmenti.A 7-year-old girl with incontinentia pigmenti and a history of multiple bacterial infections developed chronic meningitis with actinomycosis odontolyticus, which was successfully treated with long-term penicillin administration. Although all tests of immunologic function were normal in this patient, her history of recurrent and unusual infections is consistent with previous suggestions of an undefined immunodeficiency state associated with incontinentia pigmenti.- - - - - - - - - - ranking = 0.2keywords = bacterial infection (Clic here for more details about this article) |
6/9. A non-x-linked syndrome with susceptibility to severe epstein-barr virus infections.Three siblings developed severe (two) or fatal (one) infectious mononucleosis. This family differed from previously described kindreds with a susceptibility to overwhelming epstein-barr virus infections in that: (1) both males and females were affected; (2) they had a history of the recurrent bacterial infections; (3) they produced the full spectrum of antibodies to EBV in the expected range of titers; and (4) survivors recovered completely. Two of these youths, but not their parents or an unaffected sibling with mild IM, had a deficiency of natural killer activity that did not respond to preincubation of their peripheral blood mononuclear cells with interferon. NK activity may have an important role in controlling infections with EBV.- - - - - - - - - - ranking = 0.2keywords = bacterial infection (Clic here for more details about this article) |
7/9. Recurrent purulent triaditis in a patient with congenital x-linked agammaglobulinemia.A patient with congenital x-linked agammaglobulinemia, who had two separate episodes of an apparent bacterial purulent hepatic triaditis in the absence of any known local predisposing factors, is presented. These episodes may reflect the increased susceptibility of an immunodeficient patient to bacterial infections. This case demonstrates the need to consider hepatic involvement in the work-up of fevers of undetermined origin in immunodeficient patients, even in the absence of any radiologic or sonographic evidence of mechanical biliary tract obstruction.- - - - - - - - - - ranking = 0.2keywords = bacterial infection (Clic here for more details about this article) |
8/9. Evidence for exclusion of a mutation in NRAMP as the cause of familial disseminated atypical mycobacterial infection in a Maltese kindred.In mice, susceptibility to intracellular infections in inbred strains is controlled by a single locus, Lsh/Ity/Bcg, and the gene responsible has been cloned and designated Nramp (Natural resistance associated macrophage protein). We have identified a group of related children who appear to have a single gene defect, inherited recessively, which results in increased susceptibility to myocabacterial infection. The immunological defect observed in the affected children resembles that in mice homozygous for the Lsh/Ity/Bcg susceptible allele. To test the hypothesis that a mutation in NRAMP is responsible for the immunodeficiency observed in the affected children, we have typed eight markers in the region of human 2q34-q37 where NRAMP, the human homologue of Nramp, maps. We have shown discordance with the defect in one family and the chromosomes in the three affected children have different haplotypes making it unlikely that inheritance of an ancestral mutation in the NRAMP gene is the cause of increased mycobacterial susceptibility in this group of children.- - - - - - - - - - ranking = 1keywords = bacterial infection (Clic here for more details about this article) |
9/9. mutation in the signal-transducing chain of the interferon-gamma receptor and susceptibility to mycobacterial infection.IFN-gamma is critical in the immune response to mycobacterial infections, and deficits in IFN-gamma production and response have been associated with disseminated nontuberculous mycobacterial infections. Mutations in the IFN-gamma receptor ligand-binding chain (IFNgammaR1) have been shown to confer susceptibility to severe infection with nontuberculous mycobacteria. However, mutations in the IFN-gamma receptor signal-transducing chain (IFNgammaR2) have not been described. We describe a child with disseminated mycobacterium fortuitum and M. avium complex infections and absent IFN-gamma signaling due to a mutation in the extracellular domain of IFNgammaR2. in vitro cytokine production by patient PBMCs showed 75% less PHA-induced IFN-gamma production than in normal cells, while patient PHA-induced TNF-alpha production was normal. The normal augmentation of TNF-alpha production when IFN-gamma was added to endotoxin was absent from patient cells. Expression of IFNgammaR1 was normal, but there was no phosphorylation of Stat1 in response to IFN-gamma stimulation. dna sequence analysis of the gene for IFNgammaR2 showed a homozygous dinucleotide deletion at nucleotides 278 and 279, resulting in a premature stop codon in the protein extracellular domain. This novel gene defect associated with disseminated nontuberculous mycobacterial infection emphasizes the critical role that IFN-gamma plays in host defense against mycobacteria.- - - - - - - - - - ranking = 1.4keywords = bacterial infection (Clic here for more details about this article) |