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Type 1 diabetes as a relapsing–remitting disease?

Nature Reviews Immunology volume 7, pages 988–994 (2007)Cite this article

Abstract

Chronic immunological processes that underlie persistent viral infections and autoimmune disorders such as multiple sclerosis can be relapsing–remitting in nature. The progressive loss of β-cell mass during the development of autoimmune type 1 diabetes (T1D) can also be non-linear, but the exact nature and kinetics of the immunological processes that govern T1D are not known. Here, we propose that the immunological process that is at the root of T1D is relapsing–remitting in nature and discuss the unresolved controversies and therapeutic implications of this hypothesis.

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Figure 1: Type 1 diabetes as a relapsing–remitting disease?
Figure 2: Repertoire evolution in type 1 diabetes as a driver for relapses.

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Author information

Author notes

  1. Matthias von Herrath and Kevan Herold: These authors contributed equally to this work.

Authors and Affiliations

  1. Matthias von Herrath is at La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.,

    Matthias von Herrath

  2. Srinath Sanda is at the Benaroya Research Institute at Virginia Mason, Seattle, Washington 98101, USA.,

    Srinath Sanda

  3. Kevan Herold is at the Yale School of Medicine, New Haven, Connecticut 06509, USA.,

    Kevan Herold

Authors
  1. Matthias von Herrath
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Corresponding authors

Correspondence to Matthias von Herrath or Kevan Herold.

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DATABASES

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Type 1 diabetes

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Glossary

Connecting peptide

(C-peptide). Insulin is synthesized by β-cells as a hormone precursor known as pro-insulin. When released from the pancreas into the blood, pro-insulin is cleaved into insulin and a small peptide known as C-peptide. C-peptide can be used as a measure of endogenous insulin secretion (one C-peptide is released for each insulin molecule secreted).

Cryptic epitope

A cryptic epitope is an antigenic peptide generated or 'unmasked' under altered conditions, such as inflammation or autophagy. When cryptic epitopes become visible to the immune system they become good candidates for eliciting an immune response responsible for autoimmune disease.

Epitope spreading

The de novo activation of (autoreactive) T cells by antigens that have been released after damage of target cells (in this context, β-cells) has occurred.

Glycaemic control

This is a medical term that refers to the typical levels of blood sugar (glucose) in a person with diabetes mellitus. Good glycaemic control, in the sense of a 'target' for treatment, has become an important goal of diabetes care.

Honeymoon phase

This is a partial remission phase in type 1 diabetes that usually begins within weeks of diagnosis, initiation of subcutaneous insulin therapy and correction of hyperglycaemia. It is characterized by a temporary reduction in insulin requirements (patients need less than 0.5 units per kg per day of insulin) and improved glycaemic control.

Intramolecular and intermolecular spreading

A term that refers to the recognition of new determinants or epitopes by T or B cells during the development of an (auto)immune response.

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von Herrath, M., Sanda, S. & Herold, K. Type 1 diabetes as a relapsing–remitting disease?. Nat Rev Immunol 7, 988–994 (2007). https://doi.org/10.1038/nri2192

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