Associations between HLA class II alleles and IgE sensitization to allergens in the Qatar Biobank cohort

Background: Allergic disorders are the consequence of IgE sensitization to allergens. Population studies have shown that certain human leukocyte antigen (HLA) alleles are associated with increased or decreased risk of developing allergy. Objective: We aimed to characterize the relationship between HLA class II allelic diversity and IgE sensitization in an understudied Arab population. Methods: We explored associations between IgE sensitization to 7 allergen mixes and mesquite (comprising 41 food or aeroallergens) and 45 common classical HLA class II alleles in a well-defined cohort of 797 individuals representing the general adult population of Qatari nationals and long-term residents. To do so, we performed HLA calling from whole genome sequencing data at 2-field resolution using 2 independent algorithms. We then applied 3 different regression models to assess either each allergen mix independently, in the context of IgE sensitization to other allergens tested, or polysensitization. Results: More than half (n 5 447) of the study participants showed IgE sensitization to at least 1 allergen, most of them (n 5 400) to aeroallergens (Phadiatop). We identified statistically significant negative and positive associations with 24 HLA class II alleles. These have been reported to confer risk or protection from variety of diseases; however, only a few have previously been associated with allergy in other populations. Conclusions: Our study reveals several new risk and protective genetic markers for allergen-specific IgE sensitization. This is a first and essential step toward a better understanding of the origins of allergic diseases in this understudied population. (J Allergy Clin Immunol Global 2023;2:100117.

Raised Trappin2/elafin Protein in Cervico-Vaginal Fluid Is a Potential Predictor of Cervical Shortening and Spontaneous Preterm Birth

Early spontaneous preterm birth is associated with inflammation/infection and shortening of the cervix. We hypothesised that cervico-vaginal production of trappin2/elafin (peptidase inhibitor 3) and cathelicidin antimicrobial peptide (cathelicidin), key components of the innate immune system, are altered in women who have a spontaneous preterm birth. The aim was to determine the relationship between cervico-vaginal fluid (CVF) trappin2/elafin and cathelicidin protein concentrations with cervical length in woman at risk of spontaneous preterm birth. Trappin2/elafin and cathelicidin were measured using ELISA in longitudinal CVF samples (taken between 13 to 30 weeks' gestation) from 74 asymptomatic high risk women (based on obstetric history) recruited prospectively. Thirty six women developed a short cervix (200 ng/ml) measured between 14+0-14+6 weeks' of pregnancy predicted women who subsequently developed a short cervix (n = 11, ROC area = 1.00, p = 0.008) within 8 weeks. Cathelicidin was not predictive of spontaneous delivery. Vitamin D status did not correlate with CVF antimicrobial peptide concentrations. Raised CVF trappin2/elafin has potential as an early pregnancy test for prediction of cervical shortening and spontaneous preterm birth. This justifies validation in a larger cohort

STIM and Orai isoform expression in pregnant human myometrium:a potential role in calcium signaling during pregnancy

Store-operated calcium (Ca2+) entry (SOCE) can be mediated by two novel proteins, STIM/Orai. We have previously demonstrated that members of the TRPC family, putative basal and store operated calcium entry channels, are present in human myometrium and regulated by labor associated stimuli IL-1β and mechanical stretch. Although STIM and Orai isoforms (1-3) have been reported in other smooth muscle cell types, there is little known about the expression or gestational regulation of STIM and Orai expression in human myometrium. Total RNA was isolated from lower segment human myometrial biopsies obtained at caesarean section from women at the time of preterm no labor (PTNL), preterm labor (PTL), term non-labor (TNL) and term with labor (TL); primary cultured human uterine smooth muscle cells, and a human myometrial cell line (hTERT-HM). STIM1-2, and Orai1-3 mRNA expression was assessed by quantitative real-time PCR. All five genes were expressed in myometrial tissue and cultured cells. Orai2 was the most abundant Orai isoform in human myometrium. Expression of STIM1-2/Orai1-3 did not alter with the onset of labor. Orai1 mRNA expression in cultured cells was enhanced by IL-1β treatment. This novel report of STIM1-2 and Orai1-3 mRNA expression in pregnant human myometrium and Orai1 regulation by IL-1β indicates a potential role for these proteins in calcium signaling in human myometrium during pregnancy