Transitional B Cells and TLR9 Responses Are Defective in Selective IgA Deficiency.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesSelective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected individuals suffering from an increased burden of autoimmunity, atopic diseases and infections. It has been shown that IgAD B cells can be induced with germinal center mimicking reactions to produce IgA. However, IgA is the most prevalent antibody in mucosal sites, where antigen-independent responses are important. Much interest has recently focused on the role of TLR9 in both naïve and mature B cell differentiation into IgA secreting plasma cells. Here, we analyze the phenotype and function of T and B cells in individuals with IgAD following IgA-inducing CpG-TLR9 stimulations. The IgAD individuals had significantly lower numbers of transitional B cells (CD19+CD24hiCD38hi) and class-switched memory B cells (CD20+CD27+IgD-) ex vivo. However, proportions of T cell populations ex vivo as well as in vitro induced T effector cells and T regulatory cells were comparable to healthy controls. After CpG stimulation, the transitional B cell defect was further enhanced, especially within its B regulatory subset expressing IL-10. Finally, CpG stimulation failed to induce IgA production in IgAD individuals. Collectively, our results demonstrate a defect of the TLR9 responses in IgAD that leads to B cell dysregulation and decreased IgA production.Icelandic Research Fund University hospital of Iceland research fun

Mapping of Signaling Pathways Linked to sIgAD Reveals Impaired IL-21 Driven STAT3 B-Cell Activation.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadObjectives: It has recently been shown that individuals with selective IgA deficiency (sIgAD) have defective B cell responses both to T cell dependent and independent mimicking stimulations. The complex intracellular signaling pathways from different stimuli leading to IgA isotype switching have not been fully elucidated. Thus, the main objective of this study was to delineate these pathways and their potential role in the immunopathology linked to sIgAD. Materials and Methods: PBMCs from 10 individuals with sIgAD and 10 healthy controls (HC) were activated in vitro via either a T cell dependent or independent mimicking stimulation. Intracellular phosphorylation of pSTAT3, pSTAT5, pSTAT6, and as pERK1/2 was evaluated in T and B cells using phosphoflow cytometry. Results: By evaluating T cell dependent cytokine driven pathways linked to IgA isotype induction we identified a defect involving an IL-21 driven STAT3 activation isolated to B cells in sIgAD individuals. However, all other signaling pathways studied were found to be normal compared to HC. In T cell dependent cytokine driven stimulations linked to IgA isotype induction the following patterns emerged: (i) IL-10 led to significant STAT3 activation in both T- and B cells; (ii) IL-4 stimulation was predominantly confined to STAT6 activation in both T- and B cells, with some effects on STAT3 activation in T-cells; (iii) as expected, of tested stimuli, IL-2 alone activated STAT5 and some STAT3 activation though in both cases only in T-cells; (iv) IL-21 induced significant activation of STAT3 in both T- and B cells, with some effects on STAT5 activation in T-cells; and finally (v) synergistic effects were noted of IL-4+IL-10 on STAT5 activation in T-cells, and possibly STAT6 in both T- and B cells. On the other hand, CPG induced T cell independent activation was confined to ERK1/2 activation in B cells. Conclusion: Our results indicate a diminished STAT3 phosphorylation following IL-21 stimulation solely in B cells from sIgAD individuals. This can represent aberrant germinal center reactions or developmental halt. Thus, our work provides further insight into the unraveling of the previously hypothesized role of IL-21 to reconstitute immunoglobulin production in primary antibody deficiencies.Icelandic Research Fund University hospital of Iceland research fun

Challenges in migrant women's maternity care in a high-income country: A population-based cohort study of maternal and perinatal outcomes

Introduction This study aims to explore maternal and perinatal outcomes of migrant women in Iceland.Material and methods This prospective population-based cohort study included women who gave birth to a singleton in Iceland between 1997 and 2018, comprising a total of 92 403 births. Migrant women were defined as women with citizenship other than Icelandic, including refugees and asylum seekers, and categorized into three groups, based on their country of citizenship Human Development Index score. The effect of country of citizenship was estimated. The main outcome measures were onset of labor, augmentation, epidural, perineum support, episiotomy, mode of birth, obstetric anal sphincter injury, postpartum hemorrhage, preterm birth, a 5-minute Apgar = 0.900) had similar or better outcomes compared with Icelandic women, whereas migrant women from countries with a lower Human Development Index score than that of Iceland (<0.900) had additionally increased odds of maternal and perinatal complications and interventions, such as emergency cesarean and postpartum hemorrhage.Conclusions Women's citizenship and country of citizenship Human Development Index scores are significantly associated with a range of maternal and perinatal complications and interventions, such as episiotomy and instrumental birth. The results indicate the need for further exploration of whether Icelandic perinatal healthcare services meet the care needs of migrant women

Antipsychotic use in pregnancy and risk of attention/ deficit-hyperactivity disorder and autism spectrum disorder: a Nordic cohort study

Background Antipsychotics are increasingly used among women of childbearing age and during pregnancy. Objective To determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders. Design Population-based cohort study, including a sibling analysis. Setting Nationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016). Participants 4 324 086 children were eligible for inclusion to the study cohort. Intervention Antipsychotic exposure in utero, assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use. Main outcome measures Non-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors. Findings Among 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero. During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD. Discussion Our findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics. Clinical implications Results regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.publishedVersio

A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a-specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb(+) polymorphonuclear cells or FcγRIIIa(+) monocytes as effector cells, but not with FcγRIIIa(-) monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy.Sanquin/PPOC-09- 025 Landsteiner Foundation for Blood Transfusion/0721 info:eu-repo/grantAgreement/EC/FP7/27853

Samfunnsoppdrag og fagmiljø. Diskurser i arbeidet med regionalisering av legers utdanning

Opprettelsen av «Finnmarksmodellen» for medisinstudiet ved Universitetet i Tromsø er planlagt å starte høsten 2019. Denne desentraliseringen vil føre til at 12 studenter ved 5. og 6. studieår vil ha undervisning, praksis og avsluttende eksamen i Finnmark. Denne oppgaven tar for seg bakgrunnen for desentraliseringen, prosessen i forkant, en gjennomgang av aktørene som deltok og til slutt en diskursanalyse

The Icelandic child mental health study. An epidemiological study of Icelandic children 2–18 years of age using the child behavior checklist as a screening instrument

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe purpose of this study was to test the applicability of a standardised procedure for assessing Icelandic children's behaviour/emotional problems and competencies, and to identify differences related to demographic variables. This study focuses upon the method of using the Child Behavior Checklist (CBCL) by Achenbach to estimate the reported prevalence by parents and adolescents of emotional and behaviour problems in children from 2-16 years of age and self-reported prevalence of adolescents from 11-18 years, selected at random from the general population, both in urban and rural areas. The information was obtained by mailing checklists with a letter to parents of children 2-10 years of age. The checklists for adolescents 11-18 years of age were distributed by teachers in school. Those adolescents who were not in school received the checklists by mail at their homes. The Child Behavior Checklists used for analyses were completed by 109 parents of 2-3 year old children; 943 parents of 4-16 year old children, and 545 non-referred adolescents from the general population. The rate of response was lowest for the youngest age group, 47%, but increased to 62% with increasing age of the child. The response rate among the adolescents answering the Youth Self Report was 64%. Comparisons with the Child Behavior Checklist from this study are presented with Dutch, American, French, Canadian, German and Chilean samples and show striking similarities in four of these countries on the behaviour/emotional problems reported

Sono Osato (far right) as a Maiden, and artists of the company, in Protée, The Original Ballet Russe, Australian tour, His Majesty's Theatre, Melbourne, April 1940 (1) [picture] /

From: Protée : choreographic tableau / by David Lichine and Henry Clifford ; music by Claude Debussy from Danses sacree et profane.; Inscription: "3W/3 (10)".; Part of the collection: Hugh P. Hall collection of photographs, 1938-1940.; Choreography by Michel Fokine ; scenery and costumes by Giorgio de Chirico ; costumes executed by B. Karinska ; scenery executed by Prince A. Schervachidze.; Also available in an electronic version via the internet at: http://nla.gov.au/nla.pic-vn4194073. One of a collection of photographs taken by Hugh P. Hall of 28 ballet productions performed by the Covent Garden Russian Ballet (toured Australia 1938-1939) and the Original Ballet Russe (toured Australia 1939-1940). These are the second and third of the three Ballets Russes companies which toured Australasia between 1936 and 1940. The photographs were taken from the auditorium during a live performance in His Majesty's Theatre, Melbourne and mounted on cardboard for display purposes. For conservation and storage, the photographs have been demounted. The original arrangement of the photographs has been recorded, and details are available from the Pictures Branch of the National Library

Familial predisposition to monoclonal gammopathy of unknown significance, Waldenström's macroglobulinemia, and multiple myeloma

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe medical literature contains reports of around 130 families with two or more cases of MM, MGUS, or WM. An Icelandic family with multiple cases of MGUS, WM, and lymphoma was first described in 1978. In vitro testing of peripheral blood lymphocytes revealed increased production of immunoglobulins in response to poke-weed mitogen in 10 out of 35 family members, referred to as hyperresponders (HR). Enhanced B-cell survival after stimulation was associated with prolonged expression of Bcl-2. A population-based cancer registry study of 218 MM patients identified 7 additional families. Nine new cases of monoclonal gammopathy were detected by the screening of 350 family members. Further testing confirmed previously identified HR in the originally described family as well as detecting new cases. Only two HR were found in the recently identified families. The long-term aim is to identify the genetic background(s) and biology predisposing to the emergence of a persistent clone of immunoglobulin-producing cells