Adrienn Markovics1*, Daniel H. Zimmerman2, Katalin Mikecz1, Ken S. Rosenthal3
This Commentary presents the background, summary, and conclusions of a recently published article on preclinical studies of disease suppression by immunomodulatory peptide vaccines in mouse models of rheumatoid arthritis (RA). RA represents one of the most comm on autoimmune diseases that severely impact the quality of life of patients and put huge burden on healthcare. Therapeutic options are available to treat RA, ranging from over-thecounter anti-inflammatory drugs to classical immunosuppressants and newer inhibitors of inflammatory cytokine pathways. Unfortunately, 30-50% of RApatients do not respond effectively to current treatments. Based on the guidelines of the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR), once a diagnosis is established, therapy should start with a conventional synthetic disease-modiyfing anti-rheumatic drug (csDMARD) such as methotrexate or leflunomide. These drugs elicit general immune suppression but side effects are very common with extended use, and several drugs in this group are contraindicated during pregnancy. If adequate remission is not achieved by csDMARDs, a biologic DMARD (bDMARD) is the next option. bDMARDs include soluble cytokine receptors, receptor antagonists, and monoclonal antibodies against single cytokines, cytokine receptors, or other cell-surface molecules. These agents primarily act by neutralizing the action ofa particular cytokine or a cell-surface receptor and as such, they are not disease-specific. Janus kinase (JAK) inhibitors represent a class of targeted synthetic DMARDs( tsDMARDs). JAK inhibitors act intracellularly and inhibit the downstream signaling of several pro-inflammatory cytokines. These therapies are not ideal because they are either limited to treating they msptoms or they ablate inflammatory pathways that are important for critical immune functions and hence suppress necessary responses that fight infections or prevent tumor development.
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