The elusive case for a role of mimicry in autoimmune diseases

Fourneau, Jean-Marie

doi:10.1016/j.molimm.2003.11.011

Cited by 45 publications

(31 citation statements)

References 53 publications

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“…[8][9][10][11][12][13][14] In contrast, the results presented here are consistent with a number of other reports in which the elusive character of the molecular mimicry hypothesis has been underlined. [15][16][17][18][19][20][21][22][23][24][25][26][27] Our past 4,5 and present data tend to exclude a causal mechanistic role for molecular mimicry in the genesis of autoimmunity. According to the molecular mimicry hypothesis, the widespread overlap between viral and bacterial proteomes and the human proteome (see Table 1 and ref.…”

Section: Resultsmentioning

confidence: 93%

Bacterial peptides are intensively present throughout the human proteome

Trost¹,

Kusalik²,

Lucchese³

et al. 2010

Self/Nonself

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Section: Resultsmentioning

confidence: 93%

Bacterial peptides are intensively present throughout the human proteome

Trost¹,

Kusalik²,

Lucchese³

et al. 2010

Self/Nonself

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“…One popular theory is that autoantigens are derived from apoptotic cells, and that, during cell apoptosis, certain self molecules undergo programmed or spontaneous modifications that render them different from the native self and thus autoantigenic. 6 Another theory is that of molecular mimicry, 7 which postulates that an immune response initially aimed at a foreign antigen from a microbial infection also targets a self antigen with shared or very similar epitopes. A similar theory is that of epitope spreading.…”

mentioning

confidence: 99%

Human Proteins with Affinity for Dermatan Sulfate Have the Propensity to Become Autoantigens

Rho

Zhang

Murali

et al. 2011

The American Journal of Pathology

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The mystery of why and how a small, seemingly disparate subset of all self molecules become functional autoantigens holds a key to understanding autoimmune diseases. Here and in a companion article in this issue, we show that affinity of self molecules to the glycosaminoglycan dermatan sulfate (DS) is a common property of autoantigens and leads to a specific autoreactive B-1a cell response. Autoimmune ANA/ENA reference sera react preferentially with DS affinity-fractionated cellular proteins. Studying patients with autoimmune diseases, we discovered patient-specific complex autoantigen patterns that are far richer and more diverse than previously thought, indicating significant pathological heterogeneity even within traditionally defined clinical entities, such as systemic lupus erythematosus. By shotgun sequencing of DS affinity-enriched proteomes extracted from cell lines, we identified approximately 200 autoantigens, both novel and previously linked to autoimmunity, including several well-known families of autoantigens related to the nucleosome, ribonucleoproteins, the cytoskeleton, and heat shock proteins. Using electron microscopy, we recognized direct interaction with dead cells as an origin of autoantigenic association of DS with self molecules. DS affinity may be a unifying property of the human autoantigen-ome (ie, totality of self molecules that can serve as functional autoantingens) and thus provides a promising tool for discovery of autoantigens, molecular diagnosis of autoimmune diseases, and development of cause-specific therapies.

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“…[17] and a role for Epstein Barr virus in MS has also been proposed [18]. Changes in lifestyle and environmental exposures associated with the development of the' modern' lifestyle appear to be an important driver of autoimmune disease.…”

Section: Failure Of Immunological Tolerance Underlies Autoimmune Diseasementioning

confidence: 99%