Bone Mineral Density in Transgender Individuals After Gonadectomy and Long-Term Gender-Affirming Hormonal Treatment

IntroductionEstablishing the influence of long-term, gender-affirming hormonal treatment (HT) on bone mineral density (BMD) in transgender individuals is important to improve the therapeutic guidelines for these individuals.AimTo examine the effect of long-term HT and gonadectomy on BMD in transgender individuals.Methods68 transwomen and 43 transmen treated with HT who had undergone gonadectomy participated in this study. Dual-energy x-ray absorptiometry (DXA) scans were performed to measure BMD at the lumbar spine and total hip. Laboratory values related to sex hormones were collected within 3 months of performing the DXA scan and analyzed.Main Outcome MeasureBMD and levels of sex hormones in transwomen and transmen.ResultsIn transwomen, the mean BMD values at the lumbar spine and total hip at the first DXA scan were, respectively, 0.99 ± 0.15 g/cm² (n = 68) and 0.94 ± 0.28 g/cm² (n = 65). In transmen, the mean BMD values at the lumbar spine and total hip at the first DXA scan were, respectively, 1.08 ± 0.16 g/cm² (n = 43) and 1.01 ± 0.18 g/cm² (n = 43). A significant decrease in total hip BMD was found in both transwomen and transmen after 15 years of HT compared with 10 years of HT (P = .02).ConclusionIn both transwomen and transmen, a decrease was observed in total hip bone mineral density after 15 years of HT compared to the first 10 years of HT.Dobrolińska M, van der Tuuk K, Vink P, et al. Bone Mineral Density in Transgender Individuals After Gonadectomy and Long-Term Gender-Affirming Hormonal Treatment. J Sex Med 2019; 16:1469–1477.     

Lack of BIC and microRNA miR-155 expression in primary cases of Burkitt lymphoma

We previously demonstrated high expression of primary-microRNA BIC (pri-miR-155) in Hodgkin lymphoma (HL) and lack of expression in most non-Hodgkin lymphoma subtypes including some Burkitt lymphoma (BL) cases. Recently, high expression of BIC was reported in BL in comparison to pediatric leukemia and normal peripheral-blood samples. In this study, we extended our series of BL cases and cell lines to examine expression of BIC using RNA in situ hybridization (ISH) and quantitative RT-PCR (qRT-PCR) and of miR-155 using Northern blotting. Both BIC RNA ISH and qRT-PCR revealed no or low levels of BIC in 25 BL tissue samples [including 7 Epstein-Barr virus (EBV)-positive cases] compared to HL and normal controls. In agreement with these findings, no miR-155 was observed in BL tissues. EBV-negative and EBV latency type I BL cell lines also showed very low BIC and miR-155 expression levels as compared to HL cell lines. Higher levels of BIC and miR-155 were detected in in vitro transformed lymphoblastoid EBV latency type III BL cell lines. An association of latency type III infection and induction of BIC was supported by consistent expression of BIC in 11 and miR-155 in 2 posttransplantation lymphoproliferative disorder (PTLD) cases. In summary, we demonstrated that expression of BIC and miR-155 is not a common finding in BL. Expression of BIC and miR-155 in 3 latency type III EBV-positive BL cell lines and in all primary PTLD cases suggests a possible role for EBV latency type III specific proteins in the induction of BIC expression.     

Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN‐I responses

Acute or chronic viral infections can lead to generalized immunosuppression. Several mechanisms, such as immunopathology of CD8⁺ T cells, inhibitory receptors, or regulatory T (Treg) cells, contribute to immune dysfunction. Moreover, patients with chronic viral infections usually do not respond to vaccination, a finding that has not been previously explained. Recently, we reported that CD169⁺ macrophages enforce viral replication, which is essential for guaranteeing antigen synthesis and efficient adaptive immune responses. In the present study, we used a chronic lymphocytic choriomeningitis virus infection mouse model to determine whether this mechanism is affected by chronic viral infection, which may impair the activation of adaptive immunity. We found that enforced viral replication of a superinfecting virus is completely blunted in chronically infected mice. This absence of enforced viral replication in CD169⁺ macrophages is not explained by CD8⁺ T‐cell‐mediated immunopathology but rather by prolonged IFN‐I responses. Consequently, the absence of viral replication impairs both antigen production and the adaptive immune response against the superinfecting virus. These findings indicate that chronic infection leads to sustained IFN‐I action, which is responsible for the absence of an antiviral immune response against a secondary viral infection.     

Induced arginine transport via cationic amino acid transporter‐1 is necessary for human T‐cell proliferation

Availability of the semiessential amino acid arginine is fundamental for the efficient function of human T lymphocytes. Tumor‐associated arginine deprivation, mainly induced by myeloid‐derived suppressor cells, is a central mechanism of tumor immune escape from T‐cell‐mediated antitumor immune responses. We thus assumed that transmembranous transport of arginine must be crucial for T‐cell function and studied which transporters are responsible for arginine influx into primary human T lymphocytes. Here, we show that activation via CD3 and CD28 induces arginine transport into primary human T cells. Both naïve and memory CD4⁺ T cells as well as CD8⁺ T cells specifically upregulated the human cationic amino acid transporter‐1 (hCAT‐1), with an enhanced and persistent expression under arginine starvation. When hCAT‐1 induction was suppressed via siRNA transfection, arginine uptake, and cellular proliferation were impaired. In summary, our results demonstrate that hCAT‐1 is a key component of efficient T‐cell activation and a novel potential target structure to modulate adaptive immune responses in tumor immunity or inflammation.