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Biomedical subjects

Rolf D Horstmann

Publications and source records attributed to Rolf D Horstmann.

3 recordsLinked to original sources

Genomewide linkage analysis identifies polymorphism in the human interferon-gamma receptor affecting Helicobacter pylori infection.

Helicobacter pylori is considered the most prevalent infectious agent among humans, and it causes gastric inflammation, gastroduodenal ulcers, and a risk of gastric cancer. We performed a genomewide linkage analysis among Senegalese siblings phenotyped for H. pylori-reactive serum immunoglobulin G. A multipoint LOD score of 3.1 was obtained at IFNGR1, the gene that encodes chain 1 of the interferon-gamma (IFN-gamma) receptor. Sequencing of IFNGR1 revealed -56C-->T, H318P, and L450P variants, which were found to be associated with high antibody concentrations. The inclusion of these in the linkage analysis raised the LOD score to 4.2. The variants were more prevalent in Africans than in whites. Our findings indicate that IFN-gamma signaling plays an essential role in human H. pylori infection, and they contribute to an explanation of the observations of high prevalences and relatively low pathogenicity of H. pylori in Africa. Moreover, they provide further support for the value of genomewide linkage studies in the analysis of susceptibility to infection and other complex genetic traits.

Antibodies, Bacterial↗

Onchocerca volvulus-exposed persons fail to produce interferon-gamma in response to O. volvulus antigen but mount proliferative responses with interleukin-5 and IL-13 production that decrease with increasing microfilarial density.

The cellular immune response to Onchocerca volvulus antigen (OvAg) was studied in 551 persons exposed to O. volvulus transmission in a hyperendemic area of Ghana, West Africa. A whole-blood assay showed that, in response to a soluble O. volvulus extract, cell proliferation, as well as interleukin (IL)-5 and IL-13 concentrations in the supernatants, were high in cultures of blood from microfilaria (mf)-negative persons and significantly decreased with increasing mf counts of the donors. Only background concentrations of interferon (IFN)-gamma were found, and these did not correlate with mf counts. In response to a mitogen, cells from all persons strongly reacted with proliferation and secretion of all 3 cytokines studied. These findings show that the response of human peripheral blood cells to OvAg does not include significant IFN-gamma production; that mf negativity is associated with IL-5 and IL-13 production but not, as previously suggested, with IFN-gamma production; and that IL-5 and IL-13 production decreases with increasing mf density.

Adolescent↗