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Peripherin-reactive antibodies in mouse, rabbit, and human blood.

ABSTRACT: 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.

SUBMITTER: Strom A

PROVIDER: S-EPMC3023150 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Peripherin-reactive antibodies in mouse, rabbit, and human blood.

Strom Alexander A 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

Journal of proteome research 20100301 3

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 k ...[more]

PMID: 20113007

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Project description:BACKGROUND: Auto-antibodies with specificity to self-antigens have been implicated in a wide variety of neurological diseases, including Parkinson's (PD) and Alzheimer's diseases, being sensitive indicators of neurodegeneration and focus for disease prevention. Of particular interest are the studies focused on the auto-immune responses to amyloidogenic proteins associated with diseases and their applications in therapeutic treatments such as vaccination with amyloid antigens and antibodies in PD, Alzheimer's disease and potentially other neurodegeneration ailments. METHODOLOGY/PRINCIPAL FINDINGS: Generated auto-antibodies towards the major amyloidogenic protein involved in PD Lewy bodies--?-synuclein and its amyloid oligomers and fibrils were measured in the blood sera of early and late PD patients and controls by using ELISA, Western blot and Biacore surface plasmon resonance. We found significantly higher antibody levels towards monomeric ?-synuclein in the blood sera of PD patients compared to controls, though the responses decreased with PD progression (P<0.0001). This indicates potential protective role of autoimmunity in maintaining the body homeostasis and clearing protein species whose disbalance may lead to amyloid assembly. There were no noticeable immune responses towards amyloid oligomers, but substantially increased levels of IgGs towards ?-synuclein amyloid fibrils both in PD patients and controls, which subsided with the disease progression (P<0.0001). Pooled IgGs from PD patients and controls interacted also with the amyloid fibrils of A? (1-40) and hen lysozyme, however the latter were recognized with lower affinity. This suggests that IgGs bind to the generic amyloid conformational epitope, displaying higher specificity towards human amyloid species associated with neurodegeneration. CONCLUSIONS/SIGNIFICANCE: Our findings may suggest the protective role of autoimmunity in PD and therefore immune reactions towards PD major amyloid protein--?-synuclein can be of value in the development of treatment and diagnostic strategies, especially during the early disease stages.

Dataset Information

Peripherin-reactive antibodies in mouse, rabbit, and human blood.

Publications

Peripherin-reactive antibodies in mouse, rabbit, and human blood.

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