ABSTRACT
Objectives: To better understand the clinical profile of patients attending a large Australian pediatric gender service. Retrospective clinical audit of patients seen at the Royal Children's Hospital Gender Service (RCHGS) over 10 years (2007-16). Setting: The RCHGS: Australia's largest pediatric gender service. Participants: Patients were eligible for inclusion if they had an appointment with the RCHGS between January 2007 - December 2016, and had either a self-reported gender which differed from what was presumed for them at birth or sought guidance regarding gender identity/expression. Main outcome measures: Demographic/developmental history, clinical presentation including information about gender identity/dysphoria, comorbidities, self-harm, suicidal ideation, gender-affirming treatment, psychosocial functioning. Results: 359 patients were first seen during the study period. Assigned females (54%) slightly outnumbered assigned males (46%), and presented at an older age (14.8 vs 12.4 years. Patients predominantly identified as transgender (87.2%) or non-binary (7.2%). Across the cohort, gender diversity was evident from a young age (median age 3), and symptoms of gender dysphoria were noted earlier in assigned males (median age 4) than assigned females (median age 11). Although 81% of patients met eligibility for GD, rates of hormonal treatment were much lower, with 29% of young people ≥10 years of age receiving puberty blocking treatment and 38% of adolescents ≥ 16 years of age receiving gender-affirming hormones (i.e. testosterone or estrogen). Many patients had mental health difficulties and/or neurodevelopment disorders, including major depressive disorder/low mood (51%), self-harm (25%), suicidal ideation (30%) and autism spectrum disorder (16%). Conclusion: This audit illustrates the complex profile and needs of transgender and gender diverse children and adolescents presenting to specialist gender services. Supplemental data for this article is available online at https://doi.org/10.1080/26895269.2021.1939221 .
ABSTRACT
The human leukocyte antigen-independent immune-modulatory potential of human mesenchymal stem cells (hMSC) makes them a promising candidate for clinical cell therapy. A better understanding of their "immune-privileged" status is therefore of high priority. Here we used Ki-67-antigen staining to estimate T-cell alloreactivity in mixed lymphocyte cultures in the presence of hMSC as second or third party. We found that the allostimulatory activity of mesenchymal stem cells (MSC) leading to an increased T-cell proliferation and interleukin-2 secretion is measurable only at low MSC/effector ratios (< or =0.1:1). Moreover, this stimulating effect could be efficiently suppressed by MSC-conditioned medium. This suggests that the "immune-privileged" status of MSC exists only when MSC-mediated downregulation of immune cell activation can overrule their own allostimulatory potential. Thus the "immune-privileged" state of MSC represents a sensitive balance of suppressing and activating effects, which should be considered in a clinical setting with limited cell amounts.
Subject(s)
Lymphocyte Activation , Mesenchymal Stem Cells/immunology , T-Lymphocytes/immunology , Humans , Interferon-gamma/pharmacology , Interferon-gamma/physiology , Interleukin-2/pharmacology , Interleukin-2/physiology , Lymphocyte Activation/drug effects , Mesenchymal Stem Cell Transplantation , Reference Values , T-Lymphocytes/drug effects , Transplantation, Homologous/immunologyABSTRACT
We investigate the in vivo and ex vivo effect of rabbit antithymocyte globulin (ATG) on myeloid dendritic cells (MDCs) and plasmacytoid dendritic cells (PDCs). After incubation with ATG and complement, the mean number of MDCs and PDCs decreases from 3,168 to 739 x 10/mL (P=0.004) and from 5,314 to 790 x 10/mL (P=0.01), respectively. In vivo ATG given as part of the conditioning regimen before allogeneic stem-cell transplantation induces a stronger reduction of circulating MDCs and PDCs than chemotherapy alone (reduction: 100% vs. 78%-98%). These data show that ATG induces depletion of circulating MDCs and PDCs, which might be in addition to the T-cell depletion a further mechanism to reduce graft-versus-host disease after allogeneic stem-cell transplantation.