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1. Identification of Potential Biomarkers of Chronic Kidney Disease in Individuals with Diabetes: Protocol for a Cross-sectional Observational Study

Author

Lecamwasam, Ashani R, Mohebbi, Mohammadreza, Ekinci, Elif I, Dwyer, Karen M, and Saffery, Richard

Subjects
Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundThe importance of identifying people with diabetes and progressive kidney dysfunction relates to the excess morbidity and mortality of this group. Rates of cardiovascular disease are much higher in people with both diabetes and kidney dysfunction than in those with only one of these conditions. By the time these people are identified in current clinical practice, proteinuria and renal dysfunction are already established, limiting the effectiveness of therapeutic interventions. The identification of an epigenetic or blood metabolite signature or gut microbiome profile may identify those with diabetes at risk of progressive chronic kidney disease, in turn providing targeted intervention to improve patient outcomes. ObjectiveThis study aims to identify potential biomarkers in people with diabetes and chronic kidney disease (CKD) associated with progressive renal injury and to distinguish between stages of chronic kidney disease. Three sources of biomarkers will be explored, including DNA methylation profiles in blood lymphocytes, the metabolomic profile of blood-derived plasma and urine, and the gut microbiome. MethodsThe cross-sectional study recruited 121 people with diabetes and varying stages (stages 1-5) of chronic kidney disease. Single-point data collection included blood, urine, and fecal samples in addition to clinical data such as anthropometric measurements and biochemical parameters. Additional information obtained from medical records included patient demographics, medical comorbidities, and medications. ResultsData collection commenced in January 2018 and was completed in June 2018. At the time of submission, 121 patients had been recruited, and 119 samples remained after quality control. There were 83 participants in the early diabetes-associated CKD group with a mean estimated glomerular filtration rate (eGFR) of 61.2 mL/min/1.73 m2 (early CKD group consisting of stage 1, 2, and 3a CKD), and 36 participants in the late diabetic CKD group with a mean eGFR of 23.9 mL/min/1.73 m2 (late CKD group, consisting of stage 3b, 4, and 5), P

Published
2020
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2. Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth

Author

Ghantous, Akram, Nusslé, Semira Gonseth, Nassar, Farah J., Spitz, Natalia, Novoloaca, Alexei, Krali, Olga, Nickels, Eric, Cahais, Vincent, Cuenin, Cyrille, Roy, Ritu, Li, Shaobo, Caron, Maxime, Lam, Dilys, Fransquet, Peter Daniel, Casement, John, Strathdee, Gordon, Pearce, Mark S., Hansen, Helen M., Lee, Hwi-Ho, Lee, Yong Sun, de Smith, Adam J., Sinnett, Daniel, Håberg, Siri Eldevik, McKay, Jill A., Nordlund, Jessica, Magnus, Per, Dwyer, Terence, Saffery, Richard, Wiemels, Joseph Leo, Munthe-Kaas, Monica Cheng, and Herceg, Zdenko

Published
2024
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5. Male autism spectrum disorder is linked to brain aromatase disruption by prenatal BPA in multimodal investigations and 10HDA ameliorates the related mouse phenotype

Author

Symeonides, Christos, Vacy, Kristina, Thomson, Sarah, Tanner, Sam, Chua, Hui Kheng, Dixit, Shilpi, Mansell, Toby, O’Hely, Martin, Novakovic, Boris, Herbstman, Julie B., Wang, Shuang, Guo, Jia, Chia, Jessalynn, Tran, Nhi Thao, Hwang, Sang Eun, Britt, Kara, Chen, Feng, Kim, Tae Hwan, Reid, Christopher A., El-Bitar, Anthony, Bernasochi, Gabriel B., Delbridge, Lea M. Durham, Harley, Vincent R., Yap, Yann W., Dewey, Deborah, Love, Chloe J., Burgner, David, Tang, Mimi L. K., Sly, Peter D., Saffery, Richard, Mueller, Jochen F., Rinehart, Nicole, Tonge, Bruce, Vuillermin, Peter, Ponsonby, Anne-Louise, and Boon, Wah Chin

Published
2024
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6. Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy

Author

Hjort, Line, Bredgaard, Sandra Stokholm, Manitta, Eleonora, Marques, Irene, Sørensen, Anja Elaine, Martino, David, Grunnet, Louise Groth, Kelstrup, Louise, Houshmand-Oeregaard, Azadeh, Clausen, Tine Dalsgaard, Mathiesen, Elisabeth Reinhardt, Olsen, Sjurdur Frodi, Saffery, Richard, Barrès, Romain, Damm, Peter, Vaag, Allan Arthur, and Dalgaard, Louise Torp

Published
2024
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7. Age-dependent associations of human milk oligosaccharides with body size and composition up to 4 years of age.

Author

Mansell, Toby, Furst, Annalee, OHely, Martin, Chang, Melinda, Ponsonby, Anne-Louise, Vuillermin, Peter, Tang, Mimi, Burgner, David, Saffery, Richard, and Bode, Lars

Subjects
2’FL, adiposity, anthropometry, growth, human milk oligosaccharides, secretor, Infant, Female, Child, Humans, Milk, Human, Oligosaccharides, Mothers, Body Size, Postpartum Period
Abstract

BACKGROUND: Human milk oligosaccharides (HMOs) are major components of human milk that may mediate its beneficial effects on infant growth. OBJECTIVES: To investigate relationships between HMO concentrations in milk at 6 wk postpartum and anthropometry to 4 y of age in human milk-fed infants. METHODS: Milk samples were collected from 292 mothers at 6 wk (median 6.0 wk; range 3.3, 11.1] postpartum in a longitudinal, population-derived cohort. Of the infants, 171 were exclusively human milk-fed to 3 mo of age and 127 to 6 mo. Concentrations of 19 HMOs were quantified using high-performance liquid chromatography. Maternal secretor status (n = 221 secretors) was determined from 2-fucosyllactose (2FL) concentration. We calculated z-scores for child weight, length, head circumference, summed triceps and subscapular skinfold thicknesses, and weight-for-length at 6 wk, 6 mo, 12 mo, and 4 y. We investigated associations of secretor status and each HMO measure with change from birth for each z-score using linear mixed-effects models. RESULTS: Maternal secretor status was not associated with anthropometric z-scores up to 4 y of age. Several HMOs were associated with z-scores at 6 wk and 6 mo, predominantly within secretor status subgroups. Higher levels of 2FL were associated with greater weight [β = 0.91 increase in z-score per SD increase log-2FL, 95% CI (0.17, 1.65)] and length [β = 1.22, (0.25, 2.20)] in children born to secretor mothers, but not body composition measures. Higher lacto-N-tetraose was associated with greater weight [β = 0.22, (0.02, 0.41)] and length (β = 0.30, (0.07, 0.53)] among children born to nonsecretor mothers. Several HMOs were associated with anthropometric measures at 12 mo and 4 y of age. CONCLUSIONS: Milk HMO composition at 6 wk postpartum is associated with several anthropometry measures up to 6 mo of age in a potential secretor status-specific manner, with largely different HMOs associating with anthropometry from 12 mo to 4 y of age.

Published
2023

8. Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

Keck, Michaela-Kristina, Sill, Martin, Wittmann, Andrea, Joshi, Piyush, Stichel, Damian, Beck, Pengbo, Okonechnikow, Konstantin, Sievers, Philipp, Wefers, Annika K, Roncaroli, Federico, Avula, Shivaram, McCabe, Martin G, Hayden, James T, Wesseling, Pieter, Øra, Ingrid, Nistér, Monica, Kranendonk, Mariëtte EG, Tops, Bastiaan BJ, Zapotocky, Michal, Zamecnik, Josef, Vasiljevic, Alexandre, Fenouil, Tanguy, Meyronet, David, von Hoff, Katja, Schüller, Ulrich, Loiseau, Hugues, Figarella-Branger, Dominique, Kramm, Christof M, Sturm, Dominik, Scheie, David, Rauramaa, Tuomas, Pesola, Jouni, Gojo, Johannes, Haberler, Christine, Brandner, Sebastian, Jacques, Tom, Sexton Oates, Alexandra, Saffery, Richard, Koscielniak, Ewa, Baker, Suzanne J, Yip, Stephen, Snuderl, Matija, Ud Din, Nasir, Samuel, David, Schramm, Kathrin, Blattner-Johnson, Mirjam, Selt, Florian, Ecker, Jonas, Milde, Till, von Deimling, Andreas, Korshunov, Andrey, Perry, Arie, Pfister, Stefan M, Sahm, Felix, Solomon, David A, and Jones, David TW

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Pediatric, Genetics, Rare Diseases, Pediatric Cancer, Cancer, Pediatric Research Initiative, Neurosciences, Brain Cancer, Brain Disorders, Child, Child, Preschool, Female, Humans, Infant, Male, Cell Cycle Proteins, Central Nervous System Neoplasms, DNA Methylation, DNA-Binding Proteins, Neuroectodermal Tumors, Primitive, RNA-Binding Proteins, Transcription Factors, Tumor Suppressor Proteins, Wnt Signaling Pathway, PLAGL1, PLAGL2, Molecular neuro-oncology, Pediatric cancer, Clinical Sciences, Neurology & Neurosurgery
Abstract

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.

Published
2023

14. A genome catalog of the early-life human skin microbiome

Author

Shen, Zeyang, Robert, Lukian, Stolpman, Milan, Che, You, Allen, Katrina J., Saffery, Richard, Walsh, Audrey, Young, Angela, Eckert, Jana, Deming, Clay, Chen, Qiong, Conlan, Sean, Laky, Karen, Li, Jenny Min, Chatman, Lindsay, Kashaf, Sara Saheb, Kong, Heidi H., Frischmeyer-Guerrerio, Pamela A., Perrett, Kirsten P., and Segre, Julia A.

Published
2023
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16. Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study

Author

Elhakeem, Ahmed, Ronkainen, Justiina, Mansell, Toby, Lange, Katherine, Mikkola, Tuija M., Mishra, Binisha H., Wahab, Rama J., Cadman, Tim, Yang, Tiffany, Burgner, David, Eriksson, Johan G., Järvelin, Marjo-Riitta, Gaillard, Romy, Jaddoe, Vincent W. V., Lehtimäki, Terho, Raitakari, Olli T., Saffery, Richard, Wake, Melissa, Wright, John, Sebert, Sylvain, and Lawlor, Deborah A.

Published
2023
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18. Early Life Environmental Factors Associated with Autism Spectrum Disorder Symptoms in Children at Age 2 Years: A Birth Cohort Study

Author

Pham, Cindy, Symeonides, Christos, O'Hely, Martin, Sly, Peter D., Knibbs, Luke D., Thomson, Sarah, Vuillermin, Peter, Saffery, Richard, and Ponsonby, Anne-Louise

Abstract

Mounting evidence finds that early life environmental factors increased the probability of autism spectrum disorder. We estimated prospective associations between early life environmental factors and autism spectrum disorder symptoms in children at the age of 2 years in a population-derived birth cohort, the Barwon Infant Study. Autism spectrum disorder symptoms at the age of 2 years strongly predicted autism spectrum disorder diagnosis by the age of 4 years (area under curve = 0.93; 95% CI (0.82, 1.00)). After adjusting for child's sex and age at the time of behavioural assessment, markers of socioeconomic disadvantage, such as lower household income and lone parental status; maternal health factors, including younger maternal age, maternal pre-pregnancy body mass index, higher gestational weight gain and prenatal maternal stress; prenatal alcohol; environmental air pollutant exposures, including particulate matter < 2.5 [mu]m at birth, child secondhand tobacco smoke exposure at 12 months, dampness/mould and home heating with oil, kerosene or diesel heaters at 2 years postnatal. Lower socioeconomic indexes for area, later birth order, higher maternal prenatal depression, and maternal smoking frequency had a dose-response relationship with autism spectrum disorder symptoms. Future studies on environmental factors and autism spectrum disorder should consider the reasons for the socioeconomic disparity and the combined impact of multiple environmental factors through common mechanistic pathways. [Written with the Barwon Infant Study Investigator Group.]

Published
2022
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20. Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits

Author

Andreassen, Ole A., Bartels, Meike, Boomsma, Dorret, Dale, Philip S., Ehli, Erik, Fernandez-Orth, Dietmar, Guxens, Mònica, Hakulinen, Christian, Harris, Kathleen Mullan, Haworth, Simon, de Hoyos, Lucía, Jaddoe, Vincent, Keltikangas-Järvinen, Liisa, Lehtimäki, Terho, Middeldorp, Christel, Min, Josine L., Mishra, Pashupati P., Njølstad, Pål Rasmus, Sunyer, Jordi, Tate, Ashley E., Timpson, Nicholas, van der Laan, Camiel, Vrijheid, Martine, Vuoksimaa, Eero, Whipp, Alyce, Ystrom, Eivind, ACTION Consortium, Barwon Infant Study investigator group, Verhoef, Ellen, Allegrini, Andrea G., Jansen, Philip R., Lange, Katherine, Wang, Carol A., Morgan, Angela T., Ahluwalia, Tarunveer S., Symeonides, Christos, Eising, Else, Franken, Marie-Christine, Hypponen, Elina, Mansell, Toby, Olislagers, Mitchell, Omerovic, Emina, Rimfeld, Kaili, Schlag, Fenja, Selzam, Saskia, Shapland, Chin Yang, Tiemeier, Henning, Whitehouse, Andrew J.O., Saffery, Richard, Bønnelykke, Klaus, Reilly, Sheena, Pennell, Craig E., Wake, Melissa, Cecil, Charlotte A.M., Plomin, Robert, Fisher, Simon E., and St. Pourcain, Beate

Published
2024
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21. Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years: a prospective birth cohort study

Author

Tang, Mimi L.K., Gray, Lawrence, Ranganathan, Sarath, Sly, Peter, Mueller, Jochen, Dwyerm, Terry, Carlin, John, Vacy, Kristina, Thomson, Sarah, Moore, Archer, Eisner, Alex, Tanner, Sam, Pham, Cindy, Saffery, Richard, Mansell, Toby, Burgner, David, Collier, Fiona, Vuillermin, Peter, O’Hely, Martin, Boon, Wah Chin, Meikle, Peter, Burugupalli, Satvika, and Ponsonby, Anne-Louise

Published
2024
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22. Emotional symptoms and inflammatory biomarkers in childhood: Associations in two Australian birth cohorts

Author

Lange, Katherine, Pham, Cindy, Fedyszyn, Izabela E., Cook, Fallon, Burgner, David P., Olsson, Craig A., Downes, Marnie, Priest, Naomi, Mansell, Toby, Tang, Mimi L.K., Ponsonby, Anne-Louise, Symeonides, Christos, Loughman, Amy, Vuillermin, Peter, Kerr, Jessica A., Gray, Lawrence, Sly, Peter D., Lycett, Kate, Carlin, John B., Saffery, Richard, Wake, Melissa, and O'Connor, Meredith

Published
2024
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23. Correction to: Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

Keck, Michaela-Kristina, Sill, Martin, Wittmann, Andrea, Joshi, Piyush, Stichel, Damian, Beck, Pengbo, Okonechnikow, Konstantin, Sievers, Philipp, Wefers, Annika K., Roncaroli, Federico, Avula, Shivaram, McCabe, Martin G., Hayden, James T., Wesseling, Pieter, Øra, Ingrid, Nistér, Monica, Kranendonk, Mariëtte E. G., Tops, Bastiaan B. J., Zapotocky, Michal, Zamecnik, Josef, Vasiljevic, Alexandre, Fenouil, Tanguy, Meyronet, David, von Hoff, Katja, Schüller, Ulrich, Loiseau, Hugues, Figarella-Branger, Dominique, Kramm, Christof M., Sturm, Dominik, Scheie, David, Rauramaa, Tuomas, Pesola, Jouni, Gojo, Johannes, Haberler, Christine, Brandner, Sebastian, Jacques, Tom, Sexton Oates, Alexandra, Saffery, Richard, Koscielniak, Ewa, Baker, Suzanne J., Yip, Stephen, Snuderl, Matija, Ud Din, Nasir, Samuel, David, Schramm, Kathrin, Blattner-Johnson, Mirjam, Selt, Florian, Ecker, Jonas, Milde, Till, von Deimling, Andreas, Korshunov, Andrey, Perry, Arie, Pfister, Stefan M., Sahm, Felix, Solomon, David A., and Jones, David T. W.

Published
2023
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29. Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts

Author

Silventoinen, Karri, Li, Weilong, Jelenkovic, Aline, Sund, Reijo, Yokoyama, Yoshie, Aaltonen, Sari, Piirtola, Maarit, Sugawara, Masumi, Tanaka, Mami, Matsumoto, Satoko, Baker, Laura A., Tuvblad, Catherine, Tynelius, Per, Rasmussen, Finn, Craig, Jeffrey M., Saffery, Richard, Willemsen, Gonneke, Bartels, Meike, van Beijsterveldt, Catharina E. M., Martin, Nicholas G., Medland, Sarah E., Montgomery, Grant W., Lichtenstein, Paul, Krueger, Robert F., McGue, Matt, Pahlen, Shandell, Christensen, Kaare, Skytthe, Axel, Kyvik, Kirsten O., Saudino, Kimberly J., Dubois, Lise, Boivin, Michel, Brendgen, Mara, Dionne, Ginette, Vitaro, Frank, Ullemar, Vilhelmina, Almqvist, Catarina, Magnusson, Patrik K. E., Corley, Robin P., Huibregtse, Brooke M., Knafo-Noam, Ariel, Mankuta, David, Abramson, Lior, Haworth, Claire M. A., Plomin, Robert, Bjerregaard-Andersen, Morten, Beck-Nielsen, Henning, Sodemann, Morten, Duncan, Glen E., Buchwald, Dedra, Burt, S. Alexandra, Klump, Kelly L., Llewellyn, Clare H., Fisher, Abigail, Boomsma, Dorret I., Sørensen, Thorkild I. A., and Kaprio, Jaakko

Published
2022
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30. Contributors

Author

Anguera, Montserrat C., primary, Anreiter, Ina, additional, Becker, Maria, additional, Caporale, Nicolò, additional, Cheng, Stephanie, additional, Cheroni, Cristina, additional, Cheung, Stephanie, additional, Ciechanover, Aaron, additional, Collar-Fernández, Coralina, additional, Dennison, Jasmine, additional, Entringer, Sonja, additional, Feldberg, Dov, additional, Fennell, Katie A., additional, Gabory, Anne, additional, Gemmati, Donato, additional, Glezerman, Marek, additional, Gorchkova, Mila, additional, Gorobets, Denis, additional, Green, Mark, additional, Halliday, Jane, additional, Hannan, Anthony J., additional, Hoffmann, Lucas B., additional, Junien, Claudine, additional, Kocur, Olena M., additional, Lahti, Jari M., additional, Legato, Marianne J., additional, Lewis, Sharon, additional, Novakovic, Boris, additional, Ornoy, Asher, additional, Ozanne, Susan, additional, Palermo, Gianpiero D., additional, Pang, Terence Y., additional, Patel, Zeenal H., additional, Peedicayil, Jacob, additional, Pisani, Luciana Pellegrini, additional, Rosenwaks, Zev, additional, Saffery, Richard, additional, Sapozhnikov, Daniel, additional, Singh, Keshav K., additional, Sokolowski, Marla B., additional, Soreq, Hermona, additional, Stucchi, Sarah, additional, Szyf, Moshe, additional, Testa, Giuseppe, additional, Tisato, Veronica, additional, Vaura, Felix, additional, Warhaftig, Gal, additional, Weinstein-Fudim, Liza, additional, Xie, Philip, additional, and Yadid, Gal, additional

Published
2023
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40. Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: a mother-offspring cohort study

Author

Mir, Sartaj Ahmad, Chen, Li, Burugupalli, Satvika, Burla, Bo, Ji, Shanshan, Smith, Adam Alexander T., Narasimhan, Kothandaraman, Ramasamy, Adaikalavan, Tan, Karen Mei-Ling, Huynh, Kevin, Giles, Corey, Mei, Ding, Wong, Gerard, Yap, Fabian, Tan, Kok Hian, Collier, Fiona, Saffery, Richard, Vuillermin, Peter, Bendt, Anne K., Burgner, David, Ponsonby, Anne-Louise, Lee, Yung Seng, Chong, Yap Seng, Gluckman, Peter D., Eriksson, Johan G., Meikle, Peter J., Wenk, Markus R., and Karnani, Neerja

Published
2022
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48. Impact of Distinct Antiandrogen Exposures on the Plasma Metabolome in Feminizing Gender-affirming Hormone Therapy.

Author

Shepherd, Rebecca, Angus, Lachlan M, Mansell, Toby, Arman, Bridget, Kim, Bo Won, Lange, Katherine, Burgner, David, Kerr, Jessica A, Pang, Ken, Zajac, Jeffrey D, Saffery, Richard, Cheung, Ada, and Novakovic, Boris

Subjects
TRANS women, SEXUAL dimorphism, AMINO acids, HORMONE therapy, SEX hormones
Abstract

Context The plasma metabolome is a functional readout of metabolic activity and is associated with phenotypes exhibiting sexual dimorphism, such as cardiovascular disease. Sex hormones are thought to play a key role in driving sexual dimorphism. Objective Gender-affirming hormone therapy (GAHT) is a cornerstone of transgender care, but longitudinal changes in the plasma metabolome with feminizing GAHT have not been described. Methods Blood samples were collected at baseline and after 3 and 6 months of GAHT from transgender women (n = 53). Participants were randomized to different anti-androgens, cyproterone acetate or spironolactone. Nuclear magnetic resonance-based metabolomics was used to measure 249 metabolic biomarkers in plasma. Additionally, we used metabolic biomarker data from an unrelated cohort of children and their parents (n = 3748) to identify sex- and age-related metabolite patterns. Results We identified 43 metabolic biomarkers altered after 6 months in both anti-androgen groups, most belonging to the very low- or low-density lipoprotein subclasses, with all but 1 showing a decrease. We observed a cyproterone acetate-specific decrease in glutamine, glycine, and alanine levels. Notably, of the metabolic biomarkers exhibiting the most abundant "sex- and age-related" pattern (higher in assigned female children and lower in assigned female adults, relative to assigned males), 80% were significantly lowered after GAHT, reflecting a shift toward the adult female profile. Conclusion Our results suggest an anti-atherogenic signature in the plasma metabolome after the first 6 months of feminizing GAHT, with cyproterone acetate also reducing specific plasma amino acids. This study provides novel insight into the metabolic changes occurring across feminizing GAHT. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Humoral and cellular immune responses in vaccinated and unvaccinated children following SARS‐CoV‐2 Omicron infection.

Author

Toh, Zheng Quan, Anderson, Jeremy, Mazarakis, Nadia, Quah, Leanne, Nguyen, Jill, Higgins, Rachel A, Do, Lien Anh Ha, Ng, Yan Yung, Jalali, Sedi, Neeland, Melanie R, McMinn, Alissa, Saffery, Richard, McNab, Sarah, McVernon, Jodie, Marcato, Adrian, Burgner, David P, Curtis, Nigel, Steer, Andrew C, Mulholland, Kim, and Pellicci, Daniel G

Subjects
VACCINATION of children, SARS-CoV-2 Omicron variant, IMMUNOLOGIC memory, IMMUNE response, ANTIBODY formation
Abstract

Objectives: The immune response in children elicited by SARS‐CoV‐2 Omicron infection alone or in combination with COVID‐19 vaccination (hybrid immunity) is poorly understood. We examined the humoral and cellular immune response following SARS‐CoV‐2 Omicron infection in unvaccinated children and children who were previously vaccinated with COVID‐19 mRNA vaccine. Methods: Participants were recruited as part of a household cohort study conducted during the Omicron predominant wave (Jan to July 2022) in Victoria, Australia. Blood samples were collected at 1, 3, 6 and 12 months following COVID‐19 diagnosis. Humoral immune responses to SARS‐CoV‐2 Spike proteins from Wuhan, Omicron BA.1, BA.4/5 and JN.1, as well as cellular immune responses to Wuhan and BA.1 were assessed. Results: A total of 43 children and 113 samples were included in the analysis. Following Omicron infection, unvaccinated children generated low antibody responses but elicited Spike‐specific CD4 and CD8 T‐cell responses. In contrast, vaccinated children infected with the Omicron variant mounted robust humoral and cellular immune responses to both ancestral strain and Omicron subvariants. Hybrid immunity persisted for at least 6 months post infection, with cellular immune memory characterised by the generation of Spike‐specific polyfunctional CD8 T‐cell responses. Conclusion: SARS‐CoV‐2 hybrid immunity in children is characterised by persisting SARS‐CoV‐2 antibodies and robust CD4 and CD8 T‐cell activation and polyfunctional responses. Our findings contribute to understanding hybrid immunity in children and may have implications regarding COVID‐19 vaccination and SARS‐CoV‐2 re‐infections. [ABSTRACT FROM AUTHOR]

Published
2024
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