Racial disparities in the distribution of Tfh cells.

A) Overall Tfh frequencies were similar between African-Americans and Caucasians. However, race related differences were observed in certain Tfh cell subsets including B, C) decreased frequencies of Tfh1 cells in African-Americans at all age ranges, and D, E) increased Tfh17 frequencies in African-Americans, a difference that was observed in all age groups. In C and E, Caucasians are represented by blue bars and African-Americans by orange bars.</p

Reagents and antibodies for Tfh panel.

Reagents and antibodies for Tfh panel.</p

Age related changes in selected T cell populations.

A, B) A decrease in naïve CD4+ and CD8+ T cells with advancing age (C, D) corresponds with an increase in central memory CD4+ and CD8+ T cells. E) Effector memory CCR4+ Tregs increase with age. Tregs, identified by gating on CD4+CD25+CD127low cells were compared based on four age groups.</p

Study population demographics.

Study population demographics.</p

Example of web-based data visualization tool.

Researchers have the ability to select reference ranges for flow cytometry panels of interest by age, gender, and race filters. This tool will calculate summary statistics on the selected population and the data may be downloaded for study. Links to cell ontology are present when applicable, and the gating strategies are available. Gating strategies and summary tables are also available.</p

Forest plot summarizing reference ranges for major lymphocyte subsets in the overall population.

References are shown for CD3+ T cells, CD4+ T cells, CD8+ T cells, Tfh cells, overall B cells, monocytes, NK cells, Tregs, and dendritic cells. Data are presented as means with 95% reference intervals calculated by non-parametric bootstrap.</p

Rationale and design of a multicenter randomized clinical trial of vestibulodynia: understanding pathophysiology and determining appropriate treatments (vestibulodynia: UPDATe)

Limited data are available to establish evidence-based management protocols for vestibulodynia (VBD), a chronic vulvar pain condition that affects approximately 14 million women in the U.S. For the purposes of the study, our group subdivided VBD subtypes that may benefit from different types of treatment: 1) VBD peripheral (VBD-p), characterized by pain localized to the vulvar vestibule and 2) VBD central (VBD-c), characterized by VBD alongside one or more other chronic overlapping pain conditions (e.g. irritable bowel syndrome, temporomandibular disorder, and fibromyalgia syndrome) that affect remote body regions. Here, we describe the rationale and design of an NIH-funded multicenter clinical trial comparing the effectiveness of topical and/or systemic medication for alleviating pain and normalizing pain- relevant biomarkers among women with VBD-p and VBD-c. Participants will be randomly assigned to one of four parallel arms: peripheral treatment with 5% lidocaine + 0.5 mg/ml 0.02% oestradiol compound cream + oral placebo pill, 2) central treatment with the tricyclic antidepressant nortriptyline + placebo cream, 3) combined peripheral cream and central pill treatments, or 4) placebo cream and placebo pill. The treatment phase will last 16 weeks, with outcome measures and biomarkers assessed at 4 time points (0, 8, 16, and 24 weeks). First, we will compare the efficacy of treatments in alleviating pain using standardized tampon insertion with a numeric rating scale and self-reported pain on the short form McGill Pain Questionnaire. Next, we will compare the efficacy of treatments in improving perceived physical, mental, and sexual health using standardized questionnaires. Finally, we will measure cytokines and microRNAs in local vaginal and circulating blood samples using multiplex assays and RNA sequencing, and determine the ability of these biomarkers to predict treatment response. This is the first multicenter randomized controlled trial to evaluate the efficacy of peripherally and centrally acting medications currently used in clinical practice for treating unique VBD subtypes based on distinct clinical and biological signatures. Vestibulodynia UPDATe is a multi-centre, two-by-two factorial designed randomized, double-blind, placebo-controlled trial registered at clinical trials.gov (NCT03844412). This work is supported by the R01 HD096331 awarded to Drs. Nackley, Rapkin, Geller and Carey by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).Key messagesPeripheral lidocaine and oestradiol and centrally-targeted nortriptyline medications are used for the treatment of pain in women with VBD, but there is a lack of data from well-powered RCTs.This two-by-two factorial RCT will test the efficacy of these medications in VBD subtypes characterized by distinct clinical characteristics and biomarker profiles.We hope that results will provide clinicians with scientific evidence of therapeutic efficacy in distinct VBD subtypes in an effort to direct and optimize treatment approaches. Peripheral lidocaine and oestradiol and centrally-targeted nortriptyline medications are used for the treatment of pain in women with VBD, but there is a lack of data from well-powered RCTs. This two-by-two factorial RCT will test the efficacy of these medications in VBD subtypes characterized by distinct clinical characteristics and biomarker profiles. We hope that results will provide clinicians with scientific evidence of therapeutic efficacy in distinct VBD subtypes in an effort to direct and optimize treatment approaches.</p

Reagents and antibodies for HIPC panels.

Reagents and antibodies for HIPC panels.</p

Racial disparities in the distribution of innate cells.

A) Classical (CD14+CD16-) monocytes were decreased and B) non-classical (CD16+CD14-) were increased in African-Americans compared with Caucasians. C) The increase in CD16+CD14- populations in African-Americans was present in all age groups. D) In each age group, the frequency of CD14+ monocytes was higher in Caucasians compared to African-Americans. E) CD16+CD56- NK cell frequencies were increased in African-Americans compared to Caucasians, and the difference became larger in the older age groups. In C, D, and E, Caucasians are represented by blue bars and African-Americans by orange bars.</p

Identification of cell subsets in the blood.

T, B, and innate cells were identified according to HIPC guidelines. The Tfh panel is not part of the HIPC guidelines and markers were selected by the study team based on published medical literature.</p