Rheumatoid Arthritis is an autoimmune disease that results in pain swelling the joints. An autoimmune disease is a condition where your immune system attacks your own tissues, in this cells and tissues lining the joints. RA involves both T cells, which directly attack other cells, and B cells which produce antibodies—in this case “auto-antibodies. RA is antigen specific, meaning that certain proteins (antigens) are targeted by the immune system. Learning which proteins these are helps us combat the disease. Over 70% of RA patients (70% is a very high proportion when it comes to disease correlation) make antibodies against a group of proteins called citrullinated proteins. The two main types of antibodies are anti-citrullinated peptide antibodies (ACPA) and anti-cyclic citrullinated peptides (anti-CCP).
Immunotherapy is a form of treatment where cells of the immune system are used as “drugs” to treat the disease. In present study an immunotherapy preparation called “Rheumavax” was tested for safety and effects on the immune response in small group of patients. Rheumavax is prepared by drawing blood from each patient, culturing the dendritic cells with citrullinated peptides, and then injecting back into the patient. Dendritic cells are a specialized kind of cell that present antigens to T cells in order trigger an immune response. If conditions are right (or wrong) when the dendritic cells are exposed to antigen they will turn off the immune response instead of turning it on, which is what the investigators are trying to do here. The purification and preparation of the dendritic cells takes about 2 days in tissue culture. The patients were divided into three groups. One group (9 patients) got a single low dose of Rheumavax cells (1 million), a second group (9 patients) got a single high dose of Rheumavax cells (5 million), and the third group (16 patients) got no Rheumavax cells. Both doses of cells were well-tolerated.
After 1 month the patients were evaluated for the state of their arthritis symptoms and for the number of autoimmune cells they had. The results showed the patients receiving Rheumavax showed at least some clinical improvement, which correlated with a decrease in active autoimmune T cells in their bodies. Reduced T cell responses were observed in both the low dose and high dose patient groups. This is exactly what the investigators had hoped for.
Even though this trial was a small one, with a simple design and outcome measurements, the results are very promising and suggest that this kind of immunotherapy with dendritic cells is worth pursuing in future trials.
Immunotherapy like this represents one form of so-called “personalized medicine” in which each individual patient is treated with a tailored therapy regimen based on their own physiology and disease conditions.
Benham H, Nel HJ, Law SC, Mehdi AM, Street S, Ramnoruth N, Pahau H, Lee BT, Ng J, G Brunck ME, Hyde C, Trouw LA, Dudek NL, Purcell AW, O’Sullivan BJ, Connolly JE, Paul SK, Lê Cao KA, and Thomas R. 2015. Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients. Sci Transl Med. Jun 3;7(290):290ra87. doi: 10.1126/scitranslmed.aaa9301.
University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.