RESEARCH - Physiopathology of natural autoantibodies: the case for regulation

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J Autoimmun. 2007 Dec;29(4):229-35.

Physiopathology of natural auto-antibodies: the case for regulation.

Zelenay S, Moraes Fontes MF, Fesel C, Demengeot J, Coutinho A.

Instituto Gulbenkian de Ciência, Rua da Quinta Grande #6, Apartado 14,

2781-901 Oeiras, Portugal.

The cause of autoimmune diseases remains unknown and, as a

consequence, disease prediction and prophylaxis are not part of

current clinical practice. Many autoimmune syndromes are accompanied

by serological evidence of autoimmunity in the form of circulating

auto-antibodies (AAb). As normal individuals produce large amounts of

AAb, exploring the main differences between such physiologic AAb and

those classified as pathogenic may provide the clues needed for new

clinical approaches to this group of disorders. Reviewing the

differential characteristics of normal and disease-associated

autoantibodies, we conclude that the problem will be best tackled if

we understand how the organism normally ensures that

autoantigen-driven B cell activation does not lead to high titers of

autoantibodies and severe autoimmunity. As natural activation of

autoreactive B cells occur by both T cell dependent and T cell

independent mechanisms, we argue that absence of clonal expansion in

normal autoreactive B cells upon activation does not result from lack

of appropriate stimulation but, rather, from the presence of negative

regulation and suppressive mechanisms.

PMID: 17967665

http://www.ncbi.nlm.nih.gov/pubmed/17967665

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