New Study Identifies PEPITEM as a Promising Regulator of Immune Activity in Inflammatory Arthritis

Findings suggest a novel, targeted approach that could help prevent rheumatoid and psoriatic arthritis without broad immune suppression.

ATLANTA – A new study published in Arthritis & Rheumatology reveals that some patients with inflammatory arthritis may have defective function in PEPITEM, a naturally occurring peptide that acts as an internal regulator of immune cell movement during inflammation. Targeting pathways related to PEPITEM showed strong potential as a new type of therapy for inflammatory arthritis.

The researchers identified dysregulation of the adiponectin–PEPITEM pathway in individuals with early-stage rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Additional preclinical models demonstrated that treatment with PEPITEM limited disease development and reduced inflammation, highlighting its potential as an early-intervention strategy.

Findings from the study highlight the role of PEPITEM in maintaining immune balance by altering the population of white blood cells (leukocytes) that migrate into inflamed joint tissue—without compromising the body’s overall immune defense. This mechanism represents a shift away from existing arthritis treatments that rely on broad immunosuppression and can leave patients more vulnerable to infection.

“These findings open an exciting avenue for arthritis therapy,” said lead author Helen M. McGettrick PhD, MSc, FHEA of the University of Birmingham. “Rather than suppressing the entire immune system, targeting PEPITEM may be able to restore tissue equilibrium in joints and promote bone strength while maintaining normal immune function.”

Given the strong biological rationale and preclinical evidence, the researchers recommend further investigation of PEPITEM-based treatments in patients with early or subclinical forms of RA and PsA. This supports a shift toward precision medicine in RA, matching patients to therapies based on specific immune-regulatory defects rather than trial-and-error escalation.

The full study, “PEPITEM Regulates the Synovial Microenvironment During Immune-Mediated Inflammatory Arthritis to Limit Disease,” can be found online ahead of print publication in Arthritis & Rheumatology.

Media Contact
Teri Arnold
Director, Public Relations & Communications
757-272-7002
tarnold@rheumatology.org

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About the American College of Rheumatology
Founded in 1934, the American College of Rheumatology (ACR) is a not-for-profit, professional association committed to advancing the specialty of rheumatology that serves nearly 10,500 physicians, health professionals, researchers and scientists worldwide. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatology professionals are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases.