An Overview of Seminal Plasma Hypersensitivity and Approach to TreatmentCan’t copy stuff from tablet. Read part about: PAR2 and dust mite. Possible protease-activated receptor-mediated epithelial barrier dysfunction.
Systemic and localized seminal plasma hypersensitivity patients exhibit divergent immunologic characteristicsProteases constitute more than 8% of all SPPs in WSP8 and can augment IgE-independent inflammatory responses by disrupting the epithelial permeability barrier and activating protease-activated receptors (PARs) on epithelial cells.9 PAR-2 activation, which has been demonstrated in response to proteases from dust mite and cockroach and in seafood workers exposed to high aerosolized levels of proteases, can augment epithelial barrier dysfunction and localized mucosal inflammation independent of specific IgE responses.9, 10 Moreover, it has been demonstrated that semen proteases such as PSA can activate PAR-2 on spermatozoa cell membranes.11 We have recently confirmed the presence of PAR-2 receptors on vaginal keratinocytes by using western blotting and flow cytometry as well as calcium influx in SPP-stimulated vaginal keratinocytes using confocal microscopy, which was blocked by a protease inhibitor (unpublished data; Ghosh D and Bernstein JA, 2014, manuscript in preparation).
Thus, PAR-2 activation in vaginal epithelium might contribute to localized SPH, although other possible mechanisms such as IgE-independent mast cell activation and neurogenic responses involving bradykinin-mediated inflammatory/pain pathways should be investigated. In addition, prostaglandins (present in a considerable amount in WSP), which can cause antigen presenting cells to release proinflammatory cytokines, may also contribute to localized vaginal inflammation, as we have observed in some cases of women with localized SPH who experience attenuation of their symptoms if they take a nonsteroidal anti-inflammatory agent before unprotected intercourse (unpublished data). Thus, these mechanisms, summarized in Fig E2 in this article's Online Repository at
www.jacionline.org, could potentially explain reactions observed in women with localized SPH in which specific IgE does not play a critical role. To conclude, our data demonstrate that although women with systemic and localized SPH have similar clinical outcomes, the mechanism(s) of action for these responses is distinctly different. Further investigation of the mechanism(s) related to localized SPH is warranted.
Fig E2Postulated mechanisms for localized SPH: Although women with systemic SPH sensitized to PSA can induce a specific serum IgE response through the classical TH2 pathway, women with localized SPH may exhibit symptoms as a result of seminal plasma proteases causing degradation of mucosal tight junctions, leading to the activation of PAR-2 receptors on epithelial cells that results in the release of proinflammatory cytokines and localized inflammation. Seminal plasma also contains high levels of prostaglandin E2 (PGE2), which can activate antigen-presenting cells (APCs) lining the inner face of the vaginal epithelium, leading to the release of proinflammatory cytokines, causing localized mucosal inflammation.
Table 2:
https://sci-hub.se/10.1111/jsm.12813#HDM, cockroach allergens or seminal protease—>PAR2–>leakage of PGE2 and other stuff. MCA is another possibility.
