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Synapsin I Identified as a Novel Brain-Specific Autoantigen
  1. Veronika M. Gitlits,
  2. John W. Sentry,
  3. Mary L.S.M. Matthew,
  4. Ian A. Smith,
  5. Ban Hock Toh
  1. From the Department of Pathology and Immunology (V.M.G., J.W.S., B.H.T.), Monash Medical School, Prahran, Victoria, Australia
  2. Baker Medical Research Institute (M.L.M., A.I.S.), Prahran, Victoria, Australia.
  1. Address correspondence to: B.H. Toh, MD, DSc, Department of Pathology and Immunology, Monash Medical School, Alfred Hospital, Commercial Rd, Prahran, Victoria 3181, Australia. E-mail ban-hock.toh{at}med.monash.edu.au
  2. This work forms part of V.M.G.'s PhD studies, which were supported by an Australian Postgraduate Award. J.W.S. received salary support from an Australian NH&MRC grant. This work was in part funded by a grant from the Australian Research Council.

Abstract

Background We report the identification and characterization of a novel 74-kd brain-specific autoantigen that is reactive with serum from a patient with discoid lupus erythematosus and chronic lymphocytic leukemia.

Methods We determined the molecular weight, tissue distribution and subcellular distribution of the autoantigen and obtained limited amino acid sequence after purification by ion-exchange chromatography and trypsin digestion.

Results We identified the 74-kd autoantigen as synapsin I on the basis of the following observations. First, the autoantigen has properties consistent with synapsin I: molecular weight of ≈74 kd, brain-specific distribution, presence in cytosol and on synaptosomes, and association with taxol-stabilized microtubules. Second, limited amino acid sequence determination after trypsin digestion of the autoantigen shows identity with synapsin I. Third, the autoimmune serum immunoblots fusion proteins that incorporate rat synapsin Ia. The autoantibodies reactive to synapsin Ia are of immunoglobulin (Ig) G and IgM class.

Conclusions This is the first report of autoantibodies that are reactive to synapsin Ia. Autoantibodies that are reactive to synapsin Ia are not restricted to discoid lupus erythematosus patients, because we found identical reactivity in two of 18 sera from dsDNA-positive systemic lupus erythematosus patients and in two of 14 rheumatoid factor-positive sera. Whether autoantibodies to synapsin I are associated with neuropsychiatric manifestations is currently unknown.

Keywords
  • Autoantibodies
  • brain-specific
  • synapsin I

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