Autoimmunity due to molecular mimicry as a cause of neurological disease

Michael C. Levin, Sang Lee, Franck Kalume, Yvette Morcos, F Dohan, Karen Hasty, Joseph C. Callaway, Joseph Zunt, Dominic M. Desiderio, John Stuart

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease1, 2. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS)1-4. There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5-7). HAM/TSP patients develop antibodies to neurons8. We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5, 9). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged7. Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS.

Original languageEnglish (US)
Pages (from-to)509-513
Number of pages5
JournalNature Medicine
Volume8
Issue number5
DOIs
StatePublished - Jan 1 2002

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Tropical Spastic Paraparesis
Molecular Mimicry
Autoimmunity
Human T-lymphotropic virus 1
Spinal Cord Diseases
Nuclear Proteins
Autoantigens
Neurology
Viruses
Multiple Sclerosis
Antibodies
Central Nervous System
Autoimmune Diseases of the Nervous System
Immunoglobulin G
Antigen-antibody reactions
Virus Diseases
Medical problems
Taxation
Autoantibodies
Autoimmune Diseases

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Autoimmunity due to molecular mimicry as a cause of neurological disease. / Levin, Michael C.; Lee, Sang; Kalume, Franck; Morcos, Yvette; Dohan, F; Hasty, Karen; Callaway, Joseph C.; Zunt, Joseph; Desiderio, Dominic M.; Stuart, John.

In: Nature Medicine, Vol. 8, No. 5, 01.01.2002, p. 509-513.

Research output: Contribution to journalArticle

Levin, MC, Lee, S, Kalume, F, Morcos, Y, Dohan, F, Hasty, K, Callaway, JC, Zunt, J, Desiderio, DM & Stuart, J 2002, 'Autoimmunity due to molecular mimicry as a cause of neurological disease', Nature Medicine, vol. 8, no. 5, pp. 509-513. https://doi.org/10.1038/nm0502-509
Levin, Michael C. ; Lee, Sang ; Kalume, Franck ; Morcos, Yvette ; Dohan, F ; Hasty, Karen ; Callaway, Joseph C. ; Zunt, Joseph ; Desiderio, Dominic M. ; Stuart, John. / Autoimmunity due to molecular mimicry as a cause of neurological disease. In: Nature Medicine. 2002 ; Vol. 8, No. 5. pp. 509-513.
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