Systemic and localized seminal plasma hypersensitivity patients exhibit divergent immunologic characteristics Debajyoti Ghosh, PhD, Jonathan A. Bernstein,

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Presentation transcript:

Systemic and localized seminal plasma hypersensitivity patients exhibit divergent immunologic characteristics Debajyoti Ghosh, PhD, Jonathan A. Bernstein, MD Journal of Allergy and Clinical Immunology Volume 134, Issue 4, Pages 969-972.e3 (October 2014) DOI: 10.1016/j.jaci.2014.05.016 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A, IgE-specific ELISA to detect serum IgE against SPPs. OD values were plotted for systemic reactors (n = 7), localized reactors (n = 12), and control subjects (n = 5). Systemic reactors showed significantly higher SPP-specific serum IgE than did localized reactors. A positive reaction is defined as OD + 3 SD greater than negative controls. No statistical difference between localized reactors and controls subjects was observed. B, ELISA inhibition using serum from 2 representative patients with systemic SPH. Fast protein liquid chromatography fractions (Fr) or WSPs were mixed with serum and placed in 96-well plates coated with WSP. Fr2A shows the greatest inhibition (∼80-200 ng/mL required for 50% inhibition, marked as 1-50). Fr2A and Fr2B, which elicit positive skin prick or intracutaneous test results in patients, contain medium-range molecular weight SPPs, including PSA (molecular weight, 31 kD). Localized reactors do not exhibit dose-dependent inhibition (data not shown). C, Beta-hexosaminidase mediator release assay. The results of this assay demonstrate that sera from patients with systemic SPH (n = 5) release more mediator in response to WSP than do sera from patients with localized SPH (n = 10) or controls, indicating the presence of functional SPP-specific IgE in systemic reactors. Mediator release was not significantly different using sera from localized reactors compared with normal controls (n = 3). Anti-FcER1 (1 ng/mL) was used as a positive control. Spon, Spontaneous mediator release. Journal of Allergy and Clinical Immunology 2014 134, 969-972.e3DOI: (10.1016/j.jaci.2014.05.016) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Flow cytometric analysis of CD4+ T-cell population before and 18 hours after SPP desensitization of women with systemic (S1 and S2; n = 2) and localized (L1 and L2; n = 2) SPH. IFN-γ–producing CD4+ cells were expressed as percentage of CD4+ cells (left panel). Absolute numbers of cells is also illustrated (right panel). A modest increase in IFN-γ–producing CD4+ cells and a modest decrease in IL-4–producing CD4+ cells were found for the systemic, but not localized, reactors. Journal of Allergy and Clinical Immunology 2014 134, 969-972.e3DOI: (10.1016/j.jaci.2014.05.016) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Postulated 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. Journal of Allergy and Clinical Immunology 2014 134, 969-972.e3DOI: (10.1016/j.jaci.2014.05.016) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions