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The Search for Immunological Biomarkers in Type 1 Diabetes Mellitus (T1DM) and Multiple Sclerosis (MS): Th40 Cells Provide a Common Autoimmune Link

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Book cover Biomarkers in Diabetes

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Abstract

Biomarkers to predict autoimmune disease onset or predict progression are sorely lacking. A specific T cell subset present in peripheral blood of human subjects and mouse models called Th40, CD4+ helper T cells that express the CD40 receptor, are emerging as diagnostic in type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS). Th40 cell number expansions predate symptoms in both T1DM and MS in human subjects. Th40 cells prove pathogenicity by transferring T1DM in the diabetes preclinical mouse model and transferring severe symptoms in the MS mouse model. Th40 cells undergo a process called TCR revision, altering TCR expression in the periphery, constituting a mechanism that increases immune diversity to invaders like viruses, but also may increase the existence of self-antigen reactive T cells. Th40 cells are indicative of systemic inflammation and in combination with other markers, HLA and chemokine receptor expressions, can be diagnostic for specific autoimmune diseases.

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Abbreviations

AAb:

Autoantibody

APC:

Antigen presenting cell

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DC:

Dendritic cell

DKA:

Diabetic ketoacidosis

GAD:

Glutamic acid decarboxylase

GWAS:

Genome-wide association studies

HLA:

Human leukocyte antigen

IAP:

Islet-associated peptide

IFNγ:

Interferon gamma

IL:

Interleukin

INS:

Insulin

LADA:

Latent autoimmune diabetes in adults

MHC:

Major histocompatibility complex

MS:

Multiple sclerosis

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

TCR:

T cell receptor

Th:

T helper

TNFα:

Tumor necrosis factor alpha

TREC:

T cell receptor excision circle

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Authors and Affiliations

  1. Department of Medicine, The University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    David H. Wagner

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  1. David H. Wagner
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  1. Department of Biomedical Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. Franklin-Wilkins Bldg, Rm 4.101, 4th Fl, Kings Coll London, Sch Biomed Health Sci, London, UK

    Victor R. Preedy

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Wagner, D.H. (2022). The Search for Immunological Biomarkers in Type 1 Diabetes Mellitus (T1DM) and Multiple Sclerosis (MS): Th40 Cells Provide a Common Autoimmune Link. In: Patel, V.B., Preedy, V.R. (eds) Biomarkers in Diabetes. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-030-81303-1_29-1

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  • DOI: https://doi.org/10.1007/978-3-030-81303-1_29-1

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