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Altered VH6-D-JH repertoire in human insulin-dependent diabetes mellitus and autoimmune idiopathic thrombocytopenic purpura
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). (Department of Cell and Molecular Biology University of Umeå, Umeå, Sweden)
Division for Clinical Immunology, Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden.
Division for Clinical Immunology, Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
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1999 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 29, no 9, 2853-2862 p.Article in journal (Refereed) Published
Abstract [en]

We have characterized the peripheral B cell repertoire in T cell-mediated insulin-dependent diabetes mellitus (IDMM) and in B cell-mediated autoimmune idiopathic thrombocytopenic purpura (AITP). The VH6-containing repertoire in adult patients with IDDM or AITP and healthy control subjects was investigated by PCR amplification using VH6- and JH-specific primers. Nucleotide sequence analysis of VH6-D-JH rearrangements showed an abnormally high frequency of somatic mutations in non-functional rearrangements from diabetic (3. 58 %) as well as AITP patients (3.18 %), compared to controls (0.4 % and 1.43 %, respectively; p < 0.05). In contrast, the mutation frequency among functional rearrangements was 2.4 - 3 times lower in patients compared to controls ( p < 0.05). Detailed analysis of the VH6 genes carrying mutations showed that the underlying mechanism for this observation is probably different for the two diseases. Analysis of D- and JH gene usage revealed additional deviations from the normal pattern. Taken together, these results suggest defects in the mechanisms controlling selection of the B cell repertoire in patients with IDDM or AITP.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 1999. Vol. 29, no 9, 2853-2862 p.
National Category
Immunology in the medical area
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URN: urn:nbn:se:umu:diva-67442DOI: 10.1002/(SICI)1521-4141(199909)29:09<2853::AID-IMMU2853>3.0.CO;2-YPubMedID: 10508260OAI: oai:DiVA.org:umu-67442DiVA: diva2:611875
Available from: 2013-03-19 Created: 2013-03-19 Last updated: 2017-12-06Bibliographically approved

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Söderström, IngegerdHillörn, ValterHolmberg, Dan

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