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Background CD151 is a cell-surface molecule of the tetraspanin family. Its lateral interaction with laminin-binding integrin É3[beta]1 is important for podocyte adhesion to the glomerular basement membrane (GBM). Deletion of Cd151 in mice induces glomerular dysfunction, with proteinuria and associated focal glomerulosclerosis, disorganisation of GBM and tubular cystic dilation. Despite this, CD151 is not routinely screened for in patients with nephrotic-range proteinuria. We aimed to better understand the relevance of CD151 in human kidney disease. Methods Next-generation sequencing (NGS) was used to detect the variant in CD151. Electron and light microscopy were used to visualise the filtration barrier in the patient kidney biopsy, and immunoreactivity of patient red blood cells to anti-CD151/MER2 antibodies was performed. Further validation of the CD151 variant as disease-causing was performed in zebrafish using CRISPR-Cas9. Results We report a young child with nail dystrophy and persistent urinary tract infections who was incidentally found to have nephrotic-range proteinuria. Through targeted NGS, a novel, homozygous truncating variant was identified in CD151, a gene rarely reported in patients with nephrotic syndrome. Electron microscopy imaging of patient kidney tissue showed thickening of GBM and podocyte effacement. Immunofluorescence of patient kidney tissue demonstrated that CD151 was significantly reduced, and we did not detect immunoreactivity to CD151/MER2 on patient red blood cells. CRISPR-Cas9 depletion of cd151 in zebrafish caused proteinuria, which was rescued by injection of wild-type CD151 mRNA, but not CD151 mRNA containing the variant sequence. Conclusions Our results indicate that a novel variant in CD151 is associated with nephrotic-range proteinuria and microscopic haematuria and provides further evidence for a role of CD151 in glomerular disease. Our work highlights a functional testing pipeline for future analysis of patient genetic variants. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Richard W. Naylor [sup.1] , Elizabeth Watson [sup.2] , Samantha Williamson [sup.3] , Rebecca Preston [sup.1] , J Bernard Davenport [sup.1] , Nicole Thornton [sup.4] , Martin Lowe [sup.5] [...]

Black gay, bisexual, and other men who have sex with men (GBM) are disproportionately affected by HIV and STIs. Safe Spaces 4 Sexual Health (SS4SH), a community-informed, status-neutral HIV/STI testing intervention combines online outreach via geo-social networking apps and social media with mobile van testing. During 2018–2019, we recruited 25 participants for interviews about their perceptions of SS4SH compared to clinic-based testing. Participants were aged 21–65 years (mean 35); 22 (88%) identified as Black/African American; 20 (80%) identified as gay; and 10 (40%) were living with HIV. Interviews were transcribed, coded, and analyzed using a modified thematic constant comparative approach. Five themes emerged; two related to perceptions of online outreach materials (participants were drawn to eye-catching and to-the-point messages and desired more diversity and representation in messages), and three related to preference for the mobile van (participants found SS4SH provided more comfort, more privacy/confidentiality, and increased accessibility and efficiency). GBM is increasingly using geo-social networking apps to meet sexual partners, and tailored online outreach has the potential to reach historically underserved populations. SS4SH is a barrier-reducing strategy that may serve as an entry to a status-neutral approach to services and help reduce stigma and normalize accessing HIV services. [ABSTRACT FROM AUTHOR]

Introduction: Homelessness is associated with an increased risk of syphilis, HIV, and other STIs and disproportionately impacts sexual and gender minorities. Method: Data for this analysis came from a longitudinal cohort study of 285 urban gay, bisexual, and other men who have sex with men (MSM). The study aimed to (1) describe the prevalence of homelessness over time (2) identify characteristics associated with homelessness, and (3) measure associations between recent homelessness and substance use and STI/HIV risk behaviors three months later. Participants were recruited from clinical and non-clinical settings and attended a baseline visit and study visits every three months for up to 18-months. Data was collected between July 2018 and September 2020. Descriptive analyses and mixed-effects logistic regression models were utilized. Results: One-third of participants (94) reported experiencing homelessness throughout the study. Homelessness was significantly and independently associated with increased risk for future drug/alcohol use before/during sex (aOR: 3.8, 95% CI: 1.7, 8.6), methamphetamine use (aOR: 6.3 95% CI: 2.6, 15.2), injection drug use (adjusted odds ratio (aOR): 3.7, 95% CI: 1.0, 13.1), and sex exchange (aOR: 12.7; 95% CI: 5.5, 29.4). Conclusion: Interventions to reduce homelessness are necessary to lower risk of substance use and STI/HIV risk behaviors. [ABSTRACT FROM AUTHOR]

Young Black gay, bisexual and other men who have sex with men (YBMSM) carry a disproportionate HIV burden perpetuated by exposure to sexual networks with higher untreated HIV prevalence and incidence. In Baltimore, these sexual networks include high utilization of geosocial networking apps (GSN-apps). Our prior work suggests these apps can be important access points for targeted interventions like PrEP. To inform online PrEP outreach we explored YBMSM GSN-app users' exposure to and discussions about PrEP while navigating apps. We actively recruited YBMSM (n = 17) age 18-24 from the GSN-app most frequently reported by MSM newly diagnosed with HIV in Baltimore. Participants were recruited through direct messaging within the GSN-app while logged-on in high HIV transmission areas. Participants completed 60-90 minute semi-structured interviews, which were analyzed using a 3-stage analytic coding strategy. While some participants had not heard of PrEP, the majority described mentions or conversations about PrEP on GSN-apps. Three themes emerged: (1) Mistrust of PrEP, (2) Association with sexual promiscuity, and (3) Concerns about lack of protection from other STIs. Proper messaging, accurate information, and education are needed to account for the negative perceptions that surround PrEP; otherwise, continued underuse among YBMSM will expand rather than reduce HIV disparities.

Mutations in GCNT2 have been associated with the rare adult i blood group phenotype with or without congenital cataract. We report a novel homozygous frameshift mutation c.1163_1166delATCA, p.(Asn388Argfs*20) as the cause of congenital cataract in two affected siblings. Blood group typing confirmed that both affected males have the rare adult i phenotype, supporting the hypothesis that the partial association of I/i phenotype and congenital cataract is due to the differential expression of GCNT2 isoforms.

Background: Black men who have sex with men (MSM) carry the greatest burden of new HIV diagnoses in the United States. Ending the HIV epidemic requires strategic, culturally specific approaches to target factors contributing to persistent HIV disparities. Setting: Safe Spaces 4 Sexual Health (SS4SH), a communityinformed HIV/sexually transmitted infection (STI) testing strategy combining mobile van testing with online outreach, was implemented over a 14-month period from 2018 to 2019 in Baltimore, MD. Methods: We evaluated the reach of MSM at high risk with high acquisition or transmission risk by SS4SH mobile van combined with online outreach as compared with the Baltimore City Health Department's venue-based mobile van (with no online outreach) operating during the same period based on the following HIV/STI testing outcome measures: (1) number of MSM HIV or STI tested, (2) new HIV diagnosis rate, (3) percent with new syphilis diagnosis, (4) percent at high risk for HIV acquisition, and (5) percent people living with HIV at high risk for transmission. Results: Over a 14-month period, SS4SH HIV/STI tested 151 MSM. Of these, 74% were Black and the mean age was 34 (SD = 10, range = 19-68). Seven percent (10/148) were new HIV diagnoses, and 10% (13/130) were diagnosed with syphilis. The Baltimore City Health Department's venue-based mobile van strategy yielded 53% (231) more MSM(71% Black, mean age 38, SD = 14, range = 15-74), but the HIV/syphilis positivity rate was significantly lower: 0.5% new HIV diagnosis rate (P, 0.001) and 0.5% with syphilis diagnosis (P, 0.001). Conclusions: Our findings suggest SS4SH combing online outreach with mobile van testing may be more effective at reaching high-risk Black MSM than venue-based mobile testing. [ABSTRACT FROM AUTHOR]

Background: The PBDX/XG gene encoding the Xga blood group antigen was described in 1994, but the genetic determinant of XG expression on RBCs was reported only in 2018. However, the frequencies of Xg(a-) individuals could not explain the rarity of anti-Xga makers. We therefore sought to elucidate the molecular basis of the Xg(a-) phenotype in people producing anti-Xga .Study Design and Methods: Two genomic DNA (gDNA) and 13 plasma-derived cell-free DNA (cfDNA) samples from anti-Xga makers were investigated (14 males and one female). PBDX/XG exon sequencing was attempted on one gDNA sample. Polymerase chain reaction assays were developed and bioinformatics used to define a suspected deletion in all samples.Results: Investigation of one gDNA sample revealed a 114-kb deletion (esv2662319) on the X chromosome that spans XG exons 4 through 10 and the downstream GYG2 gene. A 3555-bp fragment bridging this deletion was amplified to confirm its presence. Another deletion-specific polymerase chain reaction of 714 bp enabled identification of esv2662319 in both gDNA samples and eight cfDNA samples while ruling it out in one cfDNA. Males were hemizygous for esv2662319 and the female likely homozygous. Four cfDNA sample results were inconclusive, probably due to poor sample quality. Sanger sequencing recognized the recombination junctions as a heterogeneous LTR6B sequence.Conclusion: We identified a large deletion on the X chromosome, resulting in a true, tissue-wide Xgnull phenotype. This deletion was found in 10 of 11 anti-Xga makers from which DNA could be amplified. One sample remained unexplained, indicating further heterogeneity to be explored. [ABSTRACT FROM AUTHOR]