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OBJECTIVE: Induction of immune tolerance to maintain clinical control with a minimal drug regimen is a current research focus in rheumatoid arthritis (RA). Accordingly, we are developing a tolerization approach to dnaJP1, a peptide part of a pathogenic mechanism that contributes to autoimmune inflammation in RA. We undertook this study to test 2 hypotheses: 1) that mucosal induction of immune tolerance to dnaJP1 would lead to a qualitative change from a proinflammatory phenotype to a more tolerogenic functional phenotype, and 2) that immune deviation of responses to an inflammatory epitope might translate into clinical improvement. METHODS: One hundred sixty patients with active RA and with immunologic reactivity to dnaJP1 were enrolled in a pilot phase II trial. They received oral doses of 25 mg of dnaJP1 or placebo daily for 6 months. RESULTS: The dnaJP1 peptide was safe and well-tolerated. In response to treatment with dnaJP1, there was a significant reduction in the percentage of T cells producing tumor necrosis factor alpha and a corresponding trend toward an increased percentage of T cells producing interleukin-10. Coexpression of a cluster of molecules (programmed death 1 and its ligands) associated with T cell regulation was also found to be a prerequisite for successful tolerization in clinical responders. Analysis of the primary efficacy end point (meeting the American College of Rheumatology 20% improvement criteria at least once on day 112, 140, or 168) showed a difference between treatment groups that became significant in post hoc analysis using generalized estimating equations. Differences in clinical responses were also found between treatment groups on day 140 and at followup. Post hoc analysis showed that the combination of dnaJP1 and hydroxychloroquine (HCQ) was superior to the combination of HCQ and placebo. CONCLUSION: Tolerization to dnaJP1 leads to immune deviation and a trend toward clinical efficacy. Susceptibility to treatment relies on the coexpression of molecules that can down-regulate adaptive immunity. [ABSTRACT FROM AUTHOR]

Since 2015 the new insight has emerged that avoidance of food allergens increases the risk of food allergy, specifically in infants with atopic dermatitis through cutaneous sensitisation. The primary treatment of atopic dermatitis consists of treatment with topical steroids and emollients and not by dietary intervention. Today all children are advised to introduce peanut and egg before 8 months of age. Children with atopic dermatitis are advised to so between 4 and 6 months of age following weaning foods such as fruits and vegetables. Guidelines for early introduction of peanut and egg, including home introduction schedules are available use in primary and secondary care. Timely introduction of diverse and healthy complementary foods also seems to be preventive for the development of food allergy. Breastfeeding yields contradictory results on the prevention of allergic disease, but remains the preferred choice because of many other health benefits.

Self-reactive T cells have shown to have a potential role as regulators of the immune system preventing or even suppressing autoimmunity. One of the most abundant proteins that can be eluted from human HLA molecules is heat shock protein 70 (HSP70). The aims of the current study are to identify HSP70 epitopes based on published HLA elution studies and to investigate whether T cells from healthy individuals may respond to such self-epitopes. A literature search and subsequent in silico binding prediction based on theoretical MHC binding motifs resulted in the identification of seven HSP70 epitopes. PBMCs of healthy controls proliferated after incubation with two of the seven peptides (H167 and H290). Furthermore H161, H290, and H443 induced CD69 expression or production of cytokines IFNγ or TNFα in healthy controls. The identification of these naturally presented epitopes and the response they elicit in the normal immune system make them potential candidates to study during inflammatory conditions as well as in autoimmune diseases.

Progress in our understanding of the genetics and immunology of rheumatoid arthritis (RA) has translated into clinical practice with the introduction of a first generation of biologic agents that effectively interfere with the inflammatory cascade by blocking a key component. This evolution has not only changed the way we practice, but perhaps also the way we think about RA and its treatment. In our view direct manipulation of specific pathogenic pathways is increasingly being used to replace generalized pharmacological immune suppression. The next leap forward will be to develop therapeutic approaches that will lead to maintenance of disease remission with a minimal-treatment or even drug-free regimen, relying on the induction of immune tolerance rather than the suppression of the immune system. Immune tolerance has the potential to prevent tissue damage secondary to inflammatory responses while at the same time maintaining homeostasis through physiologic recognition of self and the ability to perceive and react to 'danger'. Novel therapeutic approaches are emerging from these concepts. Such therapies will hopefully be safe and efficacious, and will complement the first generation of biologic agents that are currently available.

Purpose of Review: Current therapy for juvenile rheumatic diseases is based on general immune suppression or blocking inflammatory pathways. These treatments do not induce long-term disease remission and have a risk of side effects; this is especially unfavorable in children. It is better to focus on induction of tolerance mechanisms than on suppression of inflammation. This promotes epitope specific immunotherapy as a possible safe treatment option., Recent Findings: In the search for specific peptides for immunotherapy in autoimmunity, the focus is shifting from purported triggers of disease to peptides that regulate the ongoing inflammation. These so-called 'immunomodulatory peptides' are important in every healthy immune system. Several juvenile rheumatic diseases have been linked to certain immunomodulatory peptides. In juvenile dermatomyositis, peptides from human skeletal myosin play a role in the perpetuation of the disease. In systemic lupus erythematosus, the focus is mostly on DNA-derived peptides and peptides from anti-DNA antibodies. In juvenile idiopathic arthritis, heat shock proteins have been shown to contain important immunomodulatory epitopes., Summary: Immunomodulatory peptides play an important role in juvenile rheumatic diseases. Promising candidates for immunotherapy have been identified. This opens the possibility of clinical testing in rheumatic diseases of childhood.