Can we induce tolerance in rheumatoid arthritis?

Area of Science:

• Immunology
• Rheumatology
• Gastroenterology

Background:

• Oral tolerance (OT) is effective in animal models of autoimmune diseases.
• Human studies show successful oral tolerance to KLH and Type I Collagen (CI) in SSc.
• Clinical trials of oral Type II Collagen (CII) for rheumatoid arthritis (RA) have yielded inconsistent results.

Purpose of the Study:

• To investigate the role of prostaglandin E2 (PGE2) in blocking oral tolerance induction.
• To explore strategies for enhancing oral tolerance to Type II Collagen (CII) in rheumatoid arthritis (RA).

Main Methods:

• Review of clinical studies on OT and its inhibition by NSAIDs and prednisone.
• Examination of animal models where PGE1 analogs reverse NSAID-induced OT blockade.
• Analysis of ongoing clinical trials assessing OT induction in RA patients without NSAIDs/prednisone.

Main Results:

• Inhibition of PGE2 generation by NSAIDs and prednisone blocks OT induction.
• PGE1 analogs can reverse NSAID-induced OT blockade in murine models.
• Animal studies suggest maintaining prostaglandin function is key for successful OT induction.

Conclusions:

• Maintaining normal prostaglandin function in gut-associated lymphoid tissue (GALT) may be crucial for inducing OT to CII in RA patients.
• A clinical trial is evaluating if withholding NSAIDs and prednisone allows OT induction and improves oral CII efficacy in RA.