Background: Anaphylaxis is an acute and life-threatening allergic response. Classically and most commonly, it can be mediated by the crosslinking of allergens to immunoglobulin E (IgE)- high affinity IgE receptor (FcεRI) complex found mostly on mast cells. However, there is another pathway of anaphylaxis that is less well-studied. This pathway known as the alternative pathway is mediated by IgG and its Fc gamma receptor (Fcγ). Though it was not documented in human anaphylaxis, a few studies have found that IgG-mediated anaphylaxis can happen as demonstrated in rodent models of anaphylaxis. In these studies, a variety of soluble mediators were being evaluated and they differ from each study which causes confusion in the suitability, and reliability of choice of soluble mediators to be analyzed for diagnosis or therapeutic purposes. Hence, the objective of this meta-analysis is to identify the potential soluble mediators that are involved in an IgG-mediated anaphylaxis reaction. Methods: Studies related to IgG-mediated anaphylaxis were sourced from five search engines namely PubMed, Scopus, Ovid, Cochrane Library, and Center for Agricultural Bioscience International (CABI) regardless of publication year. Relevant studies were then reviewed based on specific inclusion factors. The means and standard deviations of each soluble mediator studied were then extracted using ImageJ or Get Data Graph Digitiser software and the data were subjected to meta-analysis. Results: From our findings, we found that histamine, serotonin, platelet activating factor (PAF), β-hexosaminidase, leukotriene C4 (LTC4), mucosal mast cell protease-1 (MMCP-1), interleukins (IL)-4,-6, and-13; tumor necrosis factor alpha (TNF-α), and macrophage inflammatory protein-1α (MIP-1α) were often being analyzed. Out of these soluble mediators, histamine, PAF, β-hexosaminidase, IL-6, and-13, MIP-1α and TNF-α were more significant with positive effect size and p < 0.001. As study effect was relatively small, we performed publication bias and found that there was publication bias and this could be due to the small sample size studied. Conclusion: As such, we proposed that through meta-analysis, the potential soluble mediators involved in rodent IgG-mediated anaphylaxis to be histamine, PAF, β-hexosaminidase, IL-6 and-13 and MIP-1α, and TNF-α but will require further studies with larger sample size.
Mast cells (MCs) play a crucial role in the pathogenesis of allergic diseases due to their hypersensitive reaction to non-harmful substances that elicit an allergic response. As such, by interrupting certain signalling proteins within the signalling pathway of a MC, an allergic response may be avoided or inhibited. Compounds that attenuate the release of mediators from MCs are known as MC stabilizers. These drugs are clinically used to prevent MC effector responses towards common allergens. Although commonly prescribed clinical MC stabilizers such as disodium cromoglycate and ketotifen fumarate were used in the preventative treatment of various allergic diseases, there still remains a need of advancement towards the discovery of new MC stabilizing drugs that are able to target specific signalling molecules in order to provide better treatment option against these diseases. Among these newly discovered potential MC stabilizers, much efforts have been given to the inhibition of vital upstream signalling molecules such as spleen tyrosine kinase as well as surface receptors such as the high-affinity IgE receptor (FcεRI) and stem cell factor receptor (KIT). A recent study also reported that linker for activation of T cells (LAT) may also be an excellent molecular target for inhibiting MC degranulation. Although in most cases the exact mode of action of these molecules is yet to be elucidated, all these compounds have shown MC inhibition. Therefore, they might have potential therapeutic use in the treatment of allergies and allergy related diseases where MCs are majorly involved. Thus, this mini review will focus on summarising the potential signalling molecules or receptors that have been targeted to inhibit MC degranulation, particularly those located in the upstream signalling pathway.