title: Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients.
abstract: BACKGROUND
  Regenerating gene (Reg) product, Reg, acts as an autocrine/paracrine growth factor for beta-cell regeneration. The presence of autoimmunity against REG may affect the operative of the regenerative mechanisms in beta cells of Type 1 and Type 2 diabetes patients. We screened sera from Type 1 and Type 2 diabetes subjects for anti-REG autoantibodies, searched for correlations in the general characteristics of the subjects with the presence of anti-REG autoimmunity, and tested the attenuation of REG-induced beta-cell proliferation by the autoanitibodies.
  
  
  METHODS
  We examined the occurrence of anti-REG autoantibodies in patients' sera (265 Type 1, 368 Type 2 diabetes patients, and 75 unrelated control subjects) by Western blot analysis, and evaluated inhibitory effects of the sera on REG-stimulated beta-cell proliferation by a 5'-Bromo-2'-deoxyuridine (BrdU) incorporation assay in vitro.
  
  
  RESULTS
  Anti-REG autoantibodies were found in 24.9% of Type 1, 14.9% of Type 2 and 2.7% of control subjects (P = 0.0004). There were significant differences between the autoantibody positive and negative groups in the duration of disease in the Type 1 subjects (P = 0.0035), and the age of onset in the Type 2 subjects (P = 0.0274). The patient sera containing anti-REG autoantibodies significantly attenuated the BrdU incorporation by REG (35.6 +/- 4.06% of the control), whereas the nondiabetic sera without anti-REG autoantibodies scarcely reduced the incorporation (88.8 +/- 5.10%).
  
  
  CONCLUSIONS
  Anti-REG autoantibodies, which retard beta-cell proliferation in vitro, are found in some diabetic patients. Thus, autoimmunity to REG may be associated with the development/acceleration of diabetes in at least some patients.
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: N J
authors.initials: NJ
authors.lastname: Shervani
authors.forename: S
authors.initials: S
authors.lastname: Takasawa
authors.forename: Y
authors.initials: Y
authors.lastname: Uchigata
authors.forename: T
authors.initials: T
authors.lastname: Akiyama
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: N
authors.initials: N
authors.lastname: Noguchi
authors.forename: H
authors.initials: H
authors.lastname: Takada
authors.forename: I
authors.initials: I
authors.lastname: Takahashi
authors.forename: A
authors.initials: A
authors.lastname: Yamauchi
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: K
authors.initials: K
authors.lastname: Nata
authors.forename: H
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001973:Bromodeoxyuridine / Q000276:immunology; D002135:Calcium-Binding Proteins / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000097:blood* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology; D051847:Lithostathine; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D001323:Autoantibodies; D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D051847:Lithostathine; C497617:REG1A protein, human; D011994:Recombinant Proteins; D001973:Bromodeoxyuridine