Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

Abstract

Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.

Keywords:

• anti-idiotypic antibody response
• itolizumab
• peripheral lymphocytic counts
• proinflammatory cytokines
• rheumatoid arthritis

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This study was conducted by the Center of Molecular Immunology. We thank Dr. Alejandro López-Requena for the valuable assistance in the reviewing of this manuscript. We also thank to all patients and their families, and the staffs of all medical institutions involved in this study.

Authors´ Contributions

Conception and design of the study: Lazaro E. Aira, Patricia Hernández, Zaima Mazorra, Carmen Viada.

Clinical investigators (recruited and treated patients): Dinorah Prada, Araceli Chico, Jorge A. Gómez.

Acquisition of data: Lazaro E. Aira, Patricia Hernández, Zuyén González, Karla Fuentes, Carmen Viada.

Analysis and interpretation of data: Lazaro E. Aira, Patricia Hernández, Zaima Mazorra.

Writing and/or revision of the manuscript: Lazaro E. Aira, Patricia Hernández, Zaima Mazorra.

Final approval: Lazaro E. Aira, Patricia Hernández, Zaima Mazorra.

Supplemental Material

Supplemental data for this article can be accessed on the publisher's website.