Epitope spreading to citrullinated antigens in mouse models of autoimmune arthritis and demyelination
2008

Citrullinated Antigens in Autoimmune Arthritis and Demyelination

publication 10 minutes Evidence: moderate

Author Information

Author(s): Kidd Brian A, Ho Peggy P, Sharpe Orr, Zhao Xiaoyan, Tomooka Beren H, Kanter Jennifer L, Steinman Lawrence, Robinson William H

Primary Institution: Stanford University School of Medicine

Hypothesis

The study investigates the development and evolution of anti-citrullinated protein antibody (ACPA) responses in rodent models of rheumatoid arthritis (RA) and multiple sclerosis (MS).

Conclusion

The study suggests that anti-citrulline antibody responses develop early in collagen-induced arthritis (CIA) and experimental autoimmune encephalomyelitis (EAE), leading to the generation of neoantigens that provoke autoimmune responses.

Supporting Evidence

  • Autoantibody responses expanded to target multiple citrullinated epitopes in both CIA and EAE.
  • Immunoblotting and mass spectrometry identified previously undescribed citrullinated proteins in CIA joint and EAE brain tissue.
  • ACPA responses were observed pre-arthritis in CIA, suggesting early immune activation.

Takeaway

The study found that certain proteins in the body can change and become targets for the immune system in diseases like arthritis and multiple sclerosis, which can make the diseases worse.

Methodology

The study used synovial and myelin protein arrays to examine B cell responses to citrullinated epitopes in mouse models of RA and MS.

Limitations

The study primarily uses mouse models, which may not fully replicate human disease mechanisms.

Participant Demographics

The study involved DBA1/J and SJL/J mice as models for RA and MS, respectively.

Statistical Information

P-Value

p < 0.001

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/ar2523

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