Food Allergen Sensitisation Patterns in Omani Patients with Allergic Manifestations

Objectives: This study aimed to evaluate the relationship between food allergen sensitisation patterns and allergic manifestations in Omani patients and highlight the importance of specific immunoglobulin E (IgE) testing. Methods: This retrospective study included all patients referred due to allergic manifestations to the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, from November 2012 to November 2016. Specific IgE blood testing was performed to determine sensitisation to common foods known to cause allergic reactions. Results: A total of 164 patients were referred to SQUH over the study period, with 35.4% presenting with one allergic manifestation, 48.8% with 2–3 and 15.9% presenting with more than three manifestations. There was a family history of allergies in 70.7% of patients. Eosinophil counts and total and specific IgE levels were elevated in 18.9%, 54.9% and 73.2% of patients, respectively. Patients demonstrated sensitisation to cow milk (47.6%), wheat (41.5%), chicken eggs (34.8%), mixed tree nuts (34.1%), lentils (33.5%), peanuts (32.9%), soy (32.3%), shrimp (23.2%) and fish (15.2%). Overall, 19.5% were sensitised to a single allergen, 14% were sensitised to 2–3 and 39.6% were sensitised to more than three allergens. Almost one-third (29.3%) of patients suffered from food-induced anaphylaxis, of which 85.4% were prescribed self-injectable adrenaline. Conclusion: To the best of the authors’ knowledge, this study is the first to describe food allergen sensitisation patterns among Omani patients with allergic manifestations. In conjunction with clinical symptoms, the correct interpretation of specific IgE levels is important to diagnose food allergies and make safe decisions about reintroducing foods. Keywords: Hypersensitivity; Food Allergies; Anaphylaxis; Urticaria; Atopic Dermatitis; Asthma; Immunoglobulin E; Oman

STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles

A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1hi, but compared to their CD57− PD-1hi counterparts, express little IL-21 or IL-10 among others. Instead, CD57 expression on TFH cells marks cytotoxicity transcriptional signatures that translate into only a weak cytotoxic phenotype. Similarly, circulating PD-1+ CD57+ CD4+ T cells make less cytokine than their CD57− PD-1+ counterparts, but have a prominent cytotoxic phenotype. By analysis of responses to STAT3-dependent cytokines and cells from patients with gain- or loss-of-function STAT3 mutations, we show that CD4+ T cell cytotoxicity is STAT3-dependent. TFH formation also requires STAT3, but paradoxically, once formed, PD-1hi cells become unresponsive to STAT3. These findings suggest that changes in blood and germinal center cytotoxicity might be affected by changes in STAT3 signaling, or modulation of PD-1 by therapy.This work was supported by National Health and Medical Research Council (Australia) program grants APP1016953 and APP427620 (CGV, CCG, SGT, MCC)

Heterophile interference accounts for method-specific dsDNA antibodies in patients receiving anti-TNF treatment

To evaluate analytical explanations for the highly reported incidence of antibodies to dsDNA in patients receiving TNF antagonists. Sixty serum samples from patients receiving biological anti-TNF medication were assessed for the presence of dsDNA antibodies using three standard diagnostic platforms [ELISA, IIF and multiplex bead array (MBA)], before and after treatment to block heterophile antibodies. Results were compared with those obtained using serum samples from patients with SLE. We identified significant method-specific discrepancies in the estimation of dsDNA antibodies in patients receiving TNF antagonists. dsDNA antibodies were frequent according to ELISA and IIF, but rare according to MBA. Blockade of heterophile antibodies resulted in a significant reduction in titres of dsDNA antibodies detected by IIF. In contrast, there was a much greater consistency for dsDNA antibody results in SLE, especially for those present in high titre, and blockade of heterophile antibodies did not result in a change between the two paired samples by IIF or MBA. There is a significant method-specific variation in the detection of dsDNA antibodies in patients receiving TNF antagonists, due in part to the effects of heterophile antibodies

De novo infantile primary antiphospholipid antibody syndrome

Most autoimmune diseases are rare in infants. Early onset can represent an extreme phenotype arising from strong genetic predisposition relatively independent of environmental influence. Alternatively, neonatal autoimmunity can arise from transplacental passage of maternal pathogenic IgG autoantibodies. Distinguishing between these possible explanations is crucial for determining the prognosis in the specific patient, and has important implications for understanding pathogenesis. We report a case of neonatal thrombotic stroke associated with both cardiolipin and β2-glycoprotein I antibodies in neonatal serum but absent from cord blood and maternal serum. While the child also carried one prothrombotic allele of factor V (Leiden allele), which may have contributed to the risk of thromboembolic disease, the serological analysis represents unequivocal evidence of de novo neonatal primary phospholipid antibody syndrome

A randomized trial of serological and cellular responses to hepatitis B vaccination in chronic kidney disease

Background Chronic kidney disease (CKD) is associated with an increased risk of hepatitis B infection and impaired seroconversion to hepatitis B vaccine (HBV). Studies examining augmented vaccine schedules to enhance seroconversion have so far been inconclusive. Furthermore, the defects responsible for impaired vaccine immunity in CKD have not yet been identified. Methods We studied serological and cellular responses to HBV in CKD to identify a defect in vaccine-induced cellular responses that could account for impaired seroconversion in CKD and clarify the effects of an augmented vaccine dose schedule. We compared these results with responses to seasonal influenza vaccination (Fluvax). Results We found a clear benefit in rates and magnitude of seroconversion after an augmented 40mcg HBV dose schedule in CKD. This permitted comparison of responders and non-responders. Serological non-responders with CKD exhibited reduction in CXCR3+CCR6- CXCR5+ memory T cells at baseline. Unlike Fluvax, HBV elicited a poor plasmablast (PB) response. Both vaccinations induced activation of the CXCR3+CCR6- CCR7- subset of circulating T follicular helper cells (cTFH), although this response was impaired in CKD after HBV. Conclusions CKD confers a specific T cell defect that contributes to the impaired seroconversion to HBV.This work received support from the National Health and Medical Research Council; grant number 1016953 (MC); https://www.nhmrc. gov.au/ and The Canberra Hospital Private Practive fund (no grant number, no URL available); (MC and KK)

Determination of an Aspergillus fumigatus-Specific Immunoglobulin G Reference Range in an Adult Omani Population

Objectives: The presence of abnormally high levels of Aspergillus fumigatus-specific immunoglobulin (Ig) G antibodies can serve as a diagnostic criterion for severe conditions like allergic bronchopulmonary and chronic pulmonary aspergillosis. This study aimed to determine a reference range of A. fumigatus-specific IgG levels within a healthy adult Omani population. Methods: This study took place during November 2015 at the Sultan Qaboos University Hospital, Muscat, Oman. The sera of 125 healthy Omani blood donors were tested for A. fumigatus-specific IgG levels using an automated fluorescence enzyme immunoassay. Results: Initially, the data were not normally distributed; however, log transformation and the exclusion of four outliers resulted in an acceptable Gaussian distribution. The reference range was 2.0–68.7 mgA/L at the 2.5th and 97.5th percentiles, respectively, with 90% confidence intervals of 2.0–3.0 mgA/L and 48.0–76.0 mgA/L, respectively. Conclusion: The A. fumigatus-specific IgG reference range within a healthy adult Omani population was comparable to those reported in other populations

A randomized trial of serological and cellular responses to hepatitis B vaccination in chronic kidney disease.

BACKGROUND:Chronic kidney disease (CKD) is associated with an increased risk of hepatitis B infection and impaired seroconversion to hepatitis B vaccine (HBV). Studies examining augmented vaccine schedules to enhance seroconversion have so far been inconclusive. Furthermore, the defects responsible for impaired vaccine immunity in CKD have not yet been identified. METHODS:We studied serological and cellular responses to HBV in CKD to identify a defect in vaccine-induced cellular responses that could account for impaired seroconversion in CKD and clarify the effects of an augmented vaccine dose schedule. We compared these results with responses to seasonal influenza vaccination (Fluvax). RESULTS:We found a clear benefit in rates and magnitude of seroconversion after an augmented 40mcg HBV dose schedule in CKD. This permitted comparison of responders and non-responders. Serological non-responders with CKD exhibited reduction in CXCR3+CCR6- CXCR5+ memory T cells at baseline. Unlike Fluvax, HBV elicited a poor plasmablast (PB) response. Both vaccinations induced activation of the CXCR3+CCR6- CCR7- subset of circulating T follicular helper cells (cTFH), although this response was impaired in CKD after HBV. CONCLUSIONS:CKD confers a specific T cell defect that contributes to the impaired seroconversion to HBV

Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis

High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin