Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients.
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.
Shervani
N J
NJ
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Takasawa
S
S
Uchigata
Y
Y
Akiyama
T
T
Nakagawa
K
K
Noguchi
N
N
Takada
H
H
Takahashi
I
I
Yamauchi
A
A
Ikeda
T
T
Iwamoto
Y
Y
Nata
K
K
Okamoto
H
H
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
D001323:Autoantibodies; D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D051847:Lithostathine; C497617:REG1A protein, human; D011994:Recombinant Proteins; D001973:Bromodeoxyuridine