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Mucosal modulation of immune responses to heat shock proteins in autoimmune arthritis

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Biotherapy

Abstract

Induction of oral tolerance to antigens that are targets of self-reactive immune responses is an attractive approach to antigen-specific immune therapy of autoimmune diseases. Oral tolerization has indeed proven to be safe and effective in amelioration of autoimmune diseases in animal models. In humans, results have been somewhat controversial. The emphasis given to clinical outcome rather than to immunomodulation, and the difficulty in identifying appropriate candidate antigens contribute to the controversy. Heat shock proteins are promising targets for immune intervention. Immune reactivity to heat shock proteins has indeed been correlated with autoimmune arthritis in animal models, and abnormal immune responses to heat shock proteins have been described in human arthritis as well. Despite significant recent progress, little is known at a molecular level regarding the mechanisms which are responsible for a switch from autoimmunity to tolerance in humans. This is particularly true with respect to sequential analysis of several molecular and immunologic markers during both the course and treatment of disease. Novel approaches are currently under way to fill the gaps. We will briefly detail here the experience gained to date, and identify some of the avenues which future research will explore.

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Abbreviations

AIA:

adjuvant-induced arthritis

APC:

antigen presenting cell

CIA:

collagen-induced arthritis

EAE:

experimental encephalomyelitis

HLA:

human leukocyte antigen

Hsp:

heat shock protein

IFNγ:

interferon gamma

IL:

interleukin

MS:

multiple sclerosis

PBMC:

peripheral blood mononuclear cells

RA:

rheumatoid arthritis

TNFα:

tumor necrosis factor alpha

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Authors and Affiliations

  1. Department of Medicine, University of California, San Diego, CA, USA

    Dustan Bonnin

  2. Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, 92093-0663, La Jolla, CA, USA

    Salvatore Albani

  3. Cevis Corporation #1486-M, Sorrento Valley Blvd., 92121, San Diego, CA, USA

    Salvatore Albani

Authors
  1. Dustan Bonnin
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  2. Salvatore Albani
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Correspondence to Salvatore Albani.

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Bonnin, D., Albani, S. Mucosal modulation of immune responses to heat shock proteins in autoimmune arthritis. Biotherapy 10, 213–221 (1998). https://doi.org/10.1007/BF02678299

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