5141 - Age dependent type 1 diabetes pathogenesis Ake...

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Age dependent type 1 diabetes pathogenesis Ake Lernmark
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From C. Garrison Fathman Nature Immunology 2, 759 - 761 (2001)
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Insulitis
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Residual β -cell function in new onset Type 1 diabetes Age C-peptide level within normal range (years) At diagnosis One year Two years 0-15 20% 10% <5% 15-34 60% 55% 46% rhw 5/99
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Type 1 diabetes genes v HLA DQ2, DQ8, or both, represents almost 90% of all type 1 diabetes patients younger than 20 years of age. The risk of DQ2/8 heterozygotes decreases with increasing age. The protection of DQ6.2 is attenuated by increasing age and is lost at about 35 years of age. v Class I - INS VNTR -short tandem repeats - increase the risk by about 2-5 %. v CTLA-4 - long AT-repeats at the 5’ end UTR - increase the risk by about 2-3%. v v
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ENVIRONMENTAL FACTORS VIRUS: MUMPS,COXSACKIE, RUBELLA, ECHO, ROTA, LJUNGAN AND OTHERS. FOOD ITEMS: NITROSAMINES, MILK PROTEINS * MONOZYGOTIC TWINS 20-30% CONCORDANCE. ** ONLY 10-15% OF NEW PATIENTS HAVE A PARENT OR SIBLING WITH THE DISEASE. GESTATIONAL INFECTIONS AND ABO INCOMPATIBILITY
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VIRUS AND TYPE 1 DIABETES Coxsackie Human, mice (Yoon) Rubella Human, hamster Mumps Human Cytomegalovirus Human Rotavirus Human CBV4 T cell activation (Vbeta analysis): T1DM=controls (Varela-Calvino et al. 2001) CBV4 T cell proliferation: T1DM > controls (Juhela et al 2000) CBV4-specific T-cell epitopes: T1DM = controls (Martilla et al. 2001) No or little cross reactivity between molecular mimicry regions (Several authors)
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Autoantibody Controls ABO immunization Hyperbilirubinemia IA-2Ab 1,4% (4/288) 6,6% (10/151)* 1,6% (5/311) GAD65Ab 1,6% (5/320) 2,6% (4/151) 1,3% (4/311) ICA 0,6% (2/320) 4,0% (6/151)** 4,2% (13/311)*** Difference compared to controls: * p=0.007; ** p=0.015; *** p=0.003. All samples are cord blood.
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This note was uploaded on 03/08/2012 for the course PHARM 300 taught by Professor Staff during the Fall '11 term at Rutgers.

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5141 - Age dependent type 1 diabetes pathogenesis Ake...

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