| 51. |
- Lakshmikanth, Tadepally, et al.
(författare)
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Immune system adaptation during gender-affirming testosterone treatment
- 2024
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 633:8028, s. 155-164
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Tidskriftsartikel (refereegranskat)abstract
- Infectious, inflammatory and autoimmune conditions present differently in males and females. SARS-CoV-2 infection in naive males is associated with increased risk of death, whereas females are at increased risk of long COVID, similar to observations in other infections. Females respond more strongly to vaccines, and adverse reactions are more frequent, like most autoimmune diseases. Immunological sex differences stem from genetic, hormonal and behavioural factors but their relative importance is only partially understood. In individuals assigned female sex at birth and undergoing gender-affirming testosterone therapy (trans men), hormone concentrations change markedly but the immunological consequences are poorly understood. Here we performed longitudinal systems-level analyses in 23 trans men and found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. These findings in trans men are corroborated by sex-divergent responses in public datasets and illustrate the dynamic regulation of human immunity by sex hormones, with implications for the health of individuals undergoing hormone therapy and our understanding of sex-divergent immune responses in cisgender individuals.
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| 52. |
- Landberg, Eva, 1966-, et al.
(författare)
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Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration
- 2007
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 376:1-2, s. 220-225
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin.MethodsA method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin.ResultsThe recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (rs = 0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (rs = 0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration.ConclusionsUltrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.
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| 53. |
- Landegren, Nils, et al.
(författare)
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Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1
- 2016
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE's selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.
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| 54. |
- Lethin, Kajsa, et al.
(författare)
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Effects of 12 Months' Treatment with Testosterone Undecanoate on Markers for Erythropoietic Activity and Safety Aspects in Transgender and Cisgender Hypogonadal Men
- 2023
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Ingår i: The Journal of Applied Laboratory Medicine. - : OXFORD UNIV PRESS INC. - 2576-9456 .- 2475-7241.
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Tidskriftsartikel (refereegranskat)abstract
- Background To investigate the erythropoietic activity and safety aspects of testosterone undecanoate (TU) injections in transgender men, assigned female at birth.Methods Twenty-three men (13 hypogonadal cisgender men and 10 transgender men) who initiated TU at the study start (naive) and 15 men (10 hypogonadal cisgender men and 5 transgender men) on steady-state treatment with TU (non-naive) were included in this prospective 1-year observational study. A control group of 32 eugonadal cisgender men was investigated once at baseline. Complete blood count, testosterone in serum and saliva, and plasma lipids, and liver enzymes were assessed.Results For naive transgender men, a significant increase in hemoglobin concentration was noted (mean (SD)), 141 (8) g/L to 151 (13) g/L, while no increase was seen in naive hypogonadal cisgender men. At the end of the study, naive transgender men exhibited comparable levels of hemoglobin, hematocrit, and testosterone levels in serum and saliva to hypogonadal cisgender men, as well as to the eugonadal cisgender men. During the study, HDL-cholesterol decreased significantly in naive transgender men, 1.4 (0.4) mmol/L to 1.2 (0.4) mmol/L, P = 0.03, whereas no significant change was noted in naive hypogonadal cisgender men. Liver enzymes remained unchanged in all groups.Conclusions After 12 months of treatment with TU in naive transgender men, hemoglobin and hematocrit increased to levels within the cisgender male reference range. A slight decrease in HDL-cholesterol was seen in naive transgender men but liver enzymes remained unchanged.
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| 55. |
- Lind, Alexander, et al.
(författare)
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Anxiety, depression and quality of life in relation to SARS-CoV-2 antibodies in individuals living with diabetes during the second wave of COVID-19
- 2024
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Ingår i: Diabetes epidemiology and management. - : Elsevier. - 2666-9706. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The objective was to compare anxiety, depression, and quality of life (QoL) in individuals living with type 1 (T1D) and type 2 (T2D) diabetes with matched controls during the second wave of the COVID-19 pandemic.Methods: Via randomization, individuals living with diabetes T1D (n = 203) and T2D (n = 413), were identified during February-July 2021 through health-care registers. Population controls (n = 282) were matched for age, gender, and residential area. Questionnaires included self-assessment of anxiety, depression, QoL, and demographics in relation to SARS-CoV-2 exposure. Blood was collected through home-capillary sampling, and SARS-CoV-2 Nucleocapsid (NCP) and Spike antibodies (SC2_S1) were determined by multiplex Antibody Detection by Agglutination-PCR (ADAP) assays.Results: Younger age and health issues were related to anxiety, depression, and QoL, with no differences between the study groups. Female gender was associated with anxiety, while obesity was associated with lower QoL. The SARS-CoV-2 NCP seroprevalence was higher in T1D (8.9 %) compared to T2D (3.9 %) and controls (4.0 %), while the SARS-CoV-2 SC2_S1 seroprevalence was higher for controls (25.5 %) compared to T1D (16.8 %) and T2D (14.0 %).Conclusions: A higher SARS-CoV-2 infection rate in T1D may be explained by younger age and higher employment rate, and the associated increased risk for viral exposure.
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| 56. |
- Lobell, Anna, et al.
(författare)
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Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for. Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts. Methods: A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity. Results: We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-kappa B1 and IL23A genes in the UK and Italian cohorts respectively. Conclusions: Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
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| 57. |
- Lood, Yvonne, et al.
(författare)
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Determination of testosterone in serum and saliva by liquid chromatography-tandem mass spectrometry : An accurate and sensitive method applied on clinical and forensic samples
- 2021
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 195
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Tidskriftsartikel (refereegranskat)abstract
- A highly sensitive and accurate electrospray liquid chromatography tandem-mass spectrometry (ESI-LC-MS/MS) method for determination of testosterone in human serum and saliva was developed and validated. Accurate quantification of testosterone in human matrices is essential in diagnosis and management of androgen status in men, women and children, and in forensic investigations of suspected abuse of anabolic androgenic steroids. Chromatography was performed on an HSS-T3 C18 column with a total run-time of 5.5 min. The tandem mass spectrometry was operated in positive electrospray ionization mode with multiple reaction monitoring. Serum and saliva samples of 200 μL, were prepared by solid-phase extraction using a 96-well plate following precipitation with 200 μL methanol. 13C labeled testosterone was used as internal standard for quantification. The standard curve was linear within the range of 4-1000 pg/mL and the limit of quantification of both serum and salivary testosterone was 4 pg/mL. Accuracy were 99-101 % and 93-95 % with between-run imprecision in serum and saliva, respectively, and inter- and intra-assay coefficients of variation were less than 9.2 %. The method proved to be applicable for determination of testosterone over a wide range of concentrations in serum and saliva samples from clinical patients with various androgen disorders, healthy male and female adults as well as from forensic cases.
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| 58. |
- Lood, Yvonne, et al.
(författare)
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Relationship between testosterone in serum, saliva and urine during treatment with intramuscular testosterone undecanoate in gender dysphoria and male hypogonadism
- 2017
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Ingår i: Andrology. - Oxford : John Wiley & Sons. - 2047-2919 .- 2047-2927. ; 6:1, s. 86-93
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Tidskriftsartikel (refereegranskat)abstract
- Long-term testosterone replacement therapy is mainly monitored by trough levels of serum testosterone (S-T), while urinary testosterone (U-T) is used by forensic toxicology to evaluate testosterone doping. Testosterone in saliva (Sal-T) may provide additional information and simplify the sample collection. We aimed to investigate the relationships between testosterone measured in saliva, serum and urine during standard treatment with 1,000mg testosterone undecanoate (TU) every 12th week during 1year. This was an observational study. Males with primary and secondary hypogonadism (HG; n=23), subjects with gender dysphoria (GD FtM; n=15) and a healthy control group of men (n=32) were investigated. Sal-T, S-T and U-T were measured before and after TU injections. Sal-T was determined with Salimetrics((R)) enzyme immunoassay, S-T with Roche Elecsys((R)) testosterone II assay and U-T by gas chromatography-mass spectrometry. Sal-T correlated significantly with S-T and calculated free testosterone in both controls and patients (HG men and GD FtM), while Sal-T to U-T showed weaker correlations. Trough values of Sal-T after 12months were significantly higher in the GD FtM group (0.77 +/- 0.35nmol/L) compared to HG men (0.53 +/- 0.22nmol/L) and controls (0.46 +/- 0.15nmol/L), while no differences between S-T and U-T trough values were found. Markedly elevated concentrations of salivary testosterone, 7-14days after injection, were observed, especially in the GD FtM group. This study demonstrates that Sal-T might be a useful clinical tool to monitor long-term testosterone replacement therapy and might give additional information in forensic cases.
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| 59. |
- Lood, Yvonne
(författare)
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Testosterone Use and Abuse : Methodological Aspects in Forensic Toxicology and Clinical Diagnostics
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abuse of anabolic androgenic steroids (AAS) is widespread in society and is today a major public health problem, associated with mental and somatic adverse effects and risk behavior, such as use of other illicit drugs and criminality. Testosterone, the most important endogenous male androgen, is therapeutically used in replacement therapy but is also extensively used as a doping agent. Traditionally, testosterone abuse is detected in urine in forensic cases and in serum in clinical diagnosis and monitoring, and free bioavailable serum testosterone is calculated by formulas. Salivary testosterone is however an attractive biomarker, as testosterone in saliva is supposed to reflect free testosterone in serum. The aim of this thesis was to investigate the abuse of AAS from a forensic perspective, particularly focusing on testosterone and methodological problems and potential alternative matrices for measurements of testosterone in forensic and clinical assessments. In the first study the toxicological findings in individuals suspected of doping offences, registered in the Swedish national forensic toxicology database were investigated (paper I). In paper II, testosterone levels in serum, saliva, and urine in clinical patients during replacement therapy with testosterone undecanoate (Nebido®) were studied. Further, the sensitivity of the current procedure for detection of testosterone abuse was investigated by method comparison using isotope ratio measurement (paper III) and a quantitative LC-MS/MS method for testosterone in serum and saliva was developed and presented (paper IV). It was found that testosterone was most frequently detected in the forensic cases and co-abuse of narcotics was common among AAS abusers. Methodological problems in detection of testosterone abuse using the present procedures was identified, indicating a need for new analytical strategies. A sensitive and highly specific LC-MS/MS method was developed for determination of testosterone in serum and saliva, which was shown suitable for analysis of forensic and clinical samples. Salivary testosterone was shown to correlate well with free serum testosterone in both male and female, and a sensitive marker in testosterone therapy, especially in females. In conclusion, it was found that saliva might have a potential as an alternative matrix for detection of illicit administration of testosterone and for diagnosis and monitoring of androgenic status.
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| 60. |
- Ludvigsson, Johnny, 1943-, et al.
(författare)
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Diabetes-related autoantibodies in cord blood from children of healthy mothers have disappeared by the time the child is one year old
- 2002
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 958, s. 289-292
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies found in cord blood in children who later develop diabetes might be produced by the fetus. If so, continuous autoantibody production would still be expected in these children at one year of age. We decided to determine autoantibodies in cord blood and to see whether they persisted in these children at one year. Autoantibodies against GAD65 (glutamic acid decarboxylase) and IA-2 (tyrosine phosphatase) in cord blood were determined in 2,518 randomly selected children. Forty-nine (1.95%) were positive for GAD65 antibodies, 14 (0.56%) were positive for IA-2 antibodies, and 3 of them were positive for both GAD and IA-2. Four of the mothers of children with GAD65 autoantibodies in cord blood (8.2%) had type 1 diabetes as did 5 mothers of children with IA-2 antibodies (35.7 %), but only 0.4% of the mothers had type 1 diabetes in the autoantibody-negative group (P < 0.001). Information on infections during pregnancy was available in 2,169 pregnancies. In the autoantibody-positive group, 31.5% had an infection during pregnancy, which was more common than in the autoantibody-negative group of 500 children with the lowest values (20.1%; P < 0.04). At one year follow-up nobody of those with positive cord blood had GAD65 or IA-2 autoantibodies. We conclude that most autoantibodies found in cord blood samples of children are probably passively transferred from mother to child. Antibody screening of cord blood cannot be used to predict diabetes in the general population. Infections during pregnancy may initiate an immune process related to diabetes development.
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