Peripherin-reactive antibodies in mouse, rabbit, and human blood.
Type 1 diabetes (T1D) is an autoimmune disorder that results from the destruction of insulin-producing beta-cells in the islets of Langerhans. To date, autoimmune T-cell response and antibody reactivity to more than 20 autoantigens have been linked to this disease. Some studies have described the intermediate filament protein peripherin (PRPH) as an autoantigen associated with T1D in non-obese diabetic (NOD) mice. We evaluated immune reactivity of mouse and rabbit sera and human plasma to a 58 kDa protein expressed in RIN-m5F rat insulinoma cells. The protein was isolated using 2-DE and identified by mass spectrometry as PRPH. Antibodies from healthy humans and T1D patients, CD-1 mice, C57BL/6 mice, NOR (non-obese diabetes resistant) mice, and NOD mice reacted with PRPH on Western blots. However, antibody response to PRPH was stronger in NOD than non-autoimmune prone C57BL/6 mice. We conclude that immune reactivity to PRPH is not exclusively associated with NOD mice or human patients with T1D. Furthermore, the frequent occurrence of PRPH-reactive antibodies in mouse and human blood suggests that binding may be non-specific or could reflect the presence of natural autoantibodies against PRPH. These findings point to the need for a re-evaluation of PRPH as a T1D autoantigen in NOD mice and raise the question of the physiological relevance of such widespread immune reactivity against this peripheral nervous system protein.
Strom
Alexander
A
Chronic Disease Program, Ottawa Hospital Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Sonier
Brigitte
B
Chapman
Harold D
HD
Mojibian
Majid
M
Wang
Gen-Sheng
GS
Slatculescu
Cristina R
CR
Serreze
David V
DV
Scott
Fraser W
FW
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000378:metabolism; D045744:Cell Line, Tumor; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007340:Insulinoma / Q000276:immunology / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D009447:Neuroblastoma / Q000276:immunology / Q000378:metabolism; D064531:Peripherins; D011817:Rabbits; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism
D001323:Autoantibodies; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; D064531:Peripherins; C579005:Prph protein, mouse; C579004:Prph protein, rat