Objectives: Patients with inflammatory bowel disease (IBD) are susceptible to intestinal opportunistic infections due to both defective mucosal immunity and altered immune response resulting from immunosuppressive treatment. Microsporidia infecting the gastrointestinal tract and causing diarrhoea can potentially affect the course of IBD. Methods: Stool samples (90 IBD children and 121 healthy age-matched controls) were screened for Encephalitozoon spp. and Enterocytozoon bieneusi by microscopy and polymerase chain reaction followed by sequencing. Results: E. bieneusi genotype D was found in seven out of 90 (7.8%) IBD children. No children from the control group were infected, making the pathogen prevalence in the IBD group significant (P = 0.002). Furthermore, infection was confirmed only in patients receiving immunosuppressive treatment (P = 0.013). Conclusions: Children with IBD are at risk of intestinal E. bieneusi infection, especially when receiving immunosuppressive treatment. Therefore, microsporidia should be considered as a significant infectious agent in this group of patients.

• Klíčová slova
• Enterocytozoon bieneusi, children, immunosuppressive treatment, inflammatory bowel disease, molecular characterization,
• Publikační typ
• časopisecké články MeSH

Microsporidia are eukaryotic, obligate, intracellular protists that are emerging pathogens in immunocompromised hosts, including AIDS patients and organ transplant recipients. The efficacy of gamma interferon (IFN-gamma) for the treatment of microsporidiosis caused by Encephalitozoon cuniculi was studied by means of adoptive transfer and IFN-gamma administration in SCID mice. While the adoptive transfer of CD4(+) T cells from immunocompetent mice prolonged survival of SCID mice infected perorally with E. cuniculi, survival was not improved by adoptive transfer of CD4(+) T lymphocytes from IFN-gamma-deficient mice. The protective effect of IFN-gamma was confirmed in cytokine therapy experiments in which SCID mice receiving IFN-gamma survived significantly longer than mice receiving mock injections. The administration of serum containing specific antibodies against E. cuniculi was found to prolong the survival of concurrently IFN-gamma-treated SCID mice. The data presented in this study suggest that IFN-gamma is potentially useful as a cytokine therapy for microsporidiosis, especially in CD4(+) T-cell-deficient patients.

• MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• Encephalitozoon cuniculi imunologie   MeSH
• encephalitozoonóza imunologie   mortalita   parazitologie   terapie   MeSH
• imunoterapie MeSH
• interferon gama aplikace a dávkování   genetika   terapeutické užití   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• monoklonální protilátky imunologie   terapeutické užití   MeSH
• myši inbrední BALB C MeSH
• myši knockoutované MeSH
• myši SCID MeSH
• myši MeSH
• převzatá imunita MeSH
• specificita protilátek * MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interferon gama MeSH
• monoklonální protilátky MeSH

The Microsporidia have been reported to cause a wide range of clinical diseases particularly in patients that are immunosuppressed. They can infect virtually any organ system and cases of gastrointestinal infection, encephalitis, ocular infection, sinusitis, myositis and disseminated infection are well described in the literature. While benzimidazoles such as albendazole are active against many species of Microsporidia, these drugs do not have significant activity against Enterocytozoon bieneusi. Fumagillin, ovalicin and their analogues have been demonstrated to have antimicrosporidial activity in vitro and in animal models of microsporidiosis. Fumagillin has also been demonstrated to have efficacy in human infections due to E. bieneusi. Fumagillin is an irreversible inhibitor of methionine aminopeptidase type 2 (MetAP2). Homology cloning employing the polymerase chain reaction was used to identify the MetAP2 gene from the human pathogenic microsporidia Encephalitozoon cuniculi, Encephalitozoon hellem, Encephalitozoon intestinalis, Brachiola algerae and E. bieneusi. The full-length MetAP2 coding sequence was obtained for all of the Encephalitozoonidae. Recombinant E. cuniculi MetAP2 was produced in baculovirus and purified using chromatographic techniques. The in vitro activity and effect of the inhibitors bestatin and TNP-470 on this recombinant microsporidian MetAP2 was characterized. An in silico model of E. cuniculi MetAP2 was developed based on crystallographic data on human MetAP2. These reagents provide new tools for the development of in vitro assay systems to screen candidate compounds for use as new therapeutic agents for the treatment of microsporidiosis.

• MeSH
• aminopeptidasy chemie   genetika   metabolismus   MeSH
• Apansporoblastina enzymologie   genetika   MeSH
• Baculoviridae MeSH
• DNA primery MeSH
• druhová specificita MeSH
• fylogeneze * MeSH
• genetické vektory genetika   MeSH
• imunoblotting MeSH
• metaloendopeptidasy chemie   genetika   metabolismus   MeSH
• molekulární modely * MeSH
• molekulární sekvence - údaje MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• sekvenční seřazení MeSH
• shluková analýza MeSH
• spory hub metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• srovnávací studie MeSH
• Názvy látek
• aminopeptidasy MeSH
• DNA primery MeSH
• metaloendopeptidasy MeSH
• methionine aminopeptidase 2 MeSH Prohlížeč