MRGPRX2 sensing of cationic compounds-A bridge between nociception and skin diseases?

Mast cells are innate immune cells located at many barrier sites in the body and known to protect the host against environmental threats and to be involved in allergic diseases. More recently, new studies have investigated their roles in the regulation of skin inflammation and transmission of pain and itch sensations. Mast cell signalling through the Mas-related G protein-coupled receptor (MRGPR) X2 or its mouse orthologue MRGPRB2 has been reported to be one of the major mechanism by which mast cell can regulate such processes. MRGPRX2 and MRGPRB2 can induce mast cell degranulation upon binding to a broad panel of cationic molecules such as neuropeptides, bacteria-derived quorum sensing molecules, venom peptides, host defense peptides and, unfortunately, various FDA-approved drugs. Upon activation, mast cells release granule-associated proteases, lipids and multiple cytokines that can modulate vascular permeability, immune cells recruitment and activation status of tissue-projecting nociceptive sensory neurons (ie nociceptors). Here, we discuss the modality of MRGPRX2-dependent mast cell activation and its different consequences on the patterns of skin inflammation and associated diseases. We notably emphasize how MRGPRX2-dependent skin mast cell activation might trigger various pathological traits such as pruritus, pain and inflammation and therefore become a potential therapeutic target for inflammatory pain, itch, atopic dermatitis and drugs-induced injection site reactions.

Risk Factors Associated with Infusion Reactions to Infliximab in Chinese Patients with Inflammatory Bowel Disease: A Large Single-Center Study.

BACKGROUND This study investigated the risk factors of infliximab (IFX)-related infusion reactions (IR) in Chinese patients with inflammatory bowel disease (IBD). MATERIAL AND METHODS The medical records of 330 consecutive IBD patients treated with IFX between 2009 and 2017 were reviewed. The incidence of IR and adverse effects were recorded in detail, and the potential risk factors related to IR were analyzed by univariate and logistic regression analysis. RESULTS The 330 patients received a total of 2108 IFX infusions, with a median follow-up of 29 months. Eighteen patients (5.5%) experienced IR: 15 were immediate (2 severe) and 3 were late (0 severe). The patients who were treated with episodic IFX without concomitant IM therapy and at the 2nd IFX series (all P<0.001) had higher incidence of IR. Logistic regression revealed the 2nd IFX treatment series (OR=0.017, P<0.001) and episodic use of IFX (OR=0.113, P<0.001) as the significant predictors. Antibodies against infliximab (ATI) were highly positive in 10 of 14 patients (71%) with IR. Sixty-seven percent of patients finished infusions after IR through appropriate management. CONCLUSIONS IFX infusions were accompanied by IR in about 5% of Chinese IBD patients. Severe IR was rare. The patients with the 2nd series or episodic use of IFX should be monitored closely during infusion.