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Introduction The absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional ‘step-up’ therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis.Methods and analysis NORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure.Ethics and dissemination Ethical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences.Trial registration number NCT05180175; Pre-results. EudraCT number: 2019-002942-19.

Abstract Neutrophils play a significant role in sustaining chronic inflammation in Inflammatory Bowel Disease. The intestinal basement membrane acts as a barrier for immunological homeostasis, where the α3 and α4 chains of type IV collagen are expressed on the mucosal surface. We wanted to develop a biomarker reflecting early tissue injury, providing an opportunity for intervention. Two competitive enzyme-linked immunosorbent assays (ELISAs) quantifying human neutrophil elastase (HNE) degraded neo-epitopes of COL4A3 and COL4A4 were developed and investigated in two observational cohorts (n = 161, n = 100). A biomarker of MMP-mediated degradation of COL4A1 (C4M) was used for comparison. In Cohort 1, patients with mild endoscopic ulcerative colitis showed elevated levels of C4A3-HNE compared to those with severe disease. C4M had a strong positive correlation with disease activity. C4A3-HNE/C4M provided superior discrimination between mild and severe endoscopic disease and negatively correlated to disease activity. In Cohort 2, C4A4-HNE and C4A4-HNE/C4M showed similar trends. C4A3-HNE and C4A4-HNE possibly reflect early intestinal tissue injury. Combining the markers with a biomarker of another α-chain of the same collagen provides information on two distinct stages of mucosal damage. These biomarkers may be used to monitor disease flare-up in patients in remission, reducing the need for frequent endoscopic procedures.

Introduction Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is ‘severe IBD’ within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death.Methods and analysis We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits.Ethics and dissemination This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.Clinical trial registration number NCT05414578; Pre-results.

Abstract Background Inflammatory bowel disease (IBD), Crohn’s disease, and ulcerative colitis are chronic autoimmune lifelong diseases with fluctuating activity over time. The treatment includes medical therapy and surgery, however, there is no definite cure. Therefore, the quest for new and supplementary treatment options is imperative to improve patients’ general health and quality of life. Physical activity and exercise have been suggested to be elements in both the prevention and supplementary treatment of IBD; however, this is based on limited underpowered trials. Thus, the role of exercise as a treatment option still has to be settled. We aim to investigate the effect of a 12-week exercise intervention in adult patients with moderately active IBD on three categories of outcomes (1) disease-specific health-related quality of life (IBDQ); (2) general health status of the patients, i.e., waist circumference, disease activity by clinical scorings systems (Harvey Bradshaw Index, Simple Clinical Colitis Activity Index), blood pressure, blood lipids, and non-disease specific quality of life (EQ5D) scores; and (3) explorative outcomes on biomarkers (C-reactive protein and fecal calprotectin) plus different biomarkers of immunology (cytokine panel). Methods We will apply a superiority design in this open-label randomized clinical trial including 150 patients equally allocated to intervention and usual care. The intervention will be based on a 12-week aerobic exercise program and will include two supervised exercise sessions of 60 min per week, combined with one weekly home training session. We have defined a moderate exercise level as 60–80% of patients’ maximum heart rate. The patients in the intervention group will also be offered an online video lesson of 15–25 min on lifestyle guidance, and the same online video lesson will be offered in the comparator group. Questionnaires on quality of life will be forwarded electronically both at inclusion and at the end of the study, and the patients will have blood samples, and fecal samples for calprotectin at baseline, weeks 4 and 8, as well as after 12 weeks (study end). Discussion This will be a clinical trial investigating the effect of exercise on patients with Crohn’s disease and ulcerative colitis. This trial will add to the evidence on the possible effect of exercise and might clarify whether exercise can benefit as a supplementary treatment addendum. Thus, the trial may provide a new patient-active disease management approach. Trial registration ClinicalTrials.gov NCT04816812. Date of first registration: March 23, 2021.

Objective We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate‐treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT). Methods This exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate‐to‐high peripheral PsA disease activity, despite at least 3 months of methotrexate‐treatment, were included in a 26‐week, double‐blind, 1:1 randomized, sham‐controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose‐to‐mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using 1H Nuclear Magnetic Resonance. Results Trial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017‐0.33]) vs. 0.012 [0‐0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P

Objectives The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins.Methods This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel).Results Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p

This paper demonstrates the connections between certain cultural traits of Scandinavia, a scholarly interest in rhetorical practice and the workings of rhetoric, and a recent interest in audience-oriented research methods. Scandinavia is characterised by a tradition of practical rhetoric, egalitarianism, high trust, and low scores on power distance and masculinity in Hofstede’s culture comparison tool. This, I suggest, is reflected in an interest in the everyday pragmatic functions and workings of rhetoric, paving the way for the use of audience research.

Abstract Objectives Physical activity in paediatric and young adult patients suffering from inflammatory bowel disease (IBD) may play an important role in the overall health status. However, physical activity in these patients has not been reported using objective methods. We aimed to describe accelerometry-measured physical activity levels in paediatric and young adult IBD patients with either ulcerative colitis (UC) or Crohn’s disease (CD). Methods We recruited Danish patients with IBD aged 10–20 years in clinical remission and with a faecal calprotectin below 200 µg/mg. Physical activity was assessed using tri-axial wrist accelerometry over seven days and quantified using the activity-related acceleration derived as the conventional Euclidian Norm Minus One (ENMO) metric expressed in milli-gravity units (mg). Time spent in Moderate-to-Vigorous Physical Activity (MVPA) was classified as ENMO > 210 mg in 5 s epoch resolution (unbouted). Results We included 61 patients with a median age of 17 years [Inter Quartile Range, IQR 14–19]. The total volume of activity expressed as average acceleration (ENMO) per day was 31.5 mg (95% CI 29.1–33.9). Time spent in unbouted MVPA was 32 min per day (95% CI 26–37). There was no significant difference in activity volume between patients with UC to patients with CD, the adjusted linear regression coefficient was − 1.7 mg (95% CI –6.2–2.7). Activity volume was higher for males (36.2 mg, 95% CI 31.9–40.5) than for females (27.8 mg, 95% CI 25.6–30.0), and younger patients were more active than older patients; Activity volume in 10–13 year olds was 37.2 mg (95% CI 28.6–45.7), whereas it was 28.5 mg (95% CI 25.2–31.7) for those aged 18–20 years. Conclusions We collected tri-axial accelerometry in young patients with IBD in clinical remission, and described their level of physical activity by the conventional ENMO measure. We found no statistically significant difference in patients with UC compared to patients with CD. The volume of physical activity was higher in males compared to females, and inversely associated with age.

Background and study aims Recent evidence supports the use of pan-enteric capsule endoscopy (CE) for the diagnosis and follow-up of Crohn’s disease (CD). The aim of this study was to examine the agreement between CE and ileocolonoscopy (IC) for determining the severity and classification of lesions in ileocolonic CD. Patients and methods In a prospective blinded multicenter study, patients with suspected CD were examined with CE and IC within 2 weeks. Ninety-nine participants with a full IC and CE were included in the analysis. The ileocolonic disease severity was assessed with the Simple Endoscopic Score for Crohn’s Disease (SES-CD). Results CD was diagnosed in 30 patients with IC and CE. The mean SES-CD was 9.8 (CI 7.9–11.8) and 10.6 (CI 8.2–13.1), respectively (P = 0.69). There was a substantial agreement (ICC 0.83, CI 0.68–0.92) and a strong correlation between SES-CD assessed with IC and CE (rs = 0.78, P

Abstract Objective Convalescent plasma has been tried as therapy for various viral infections. Early observational studies of convalescent plasma treatment for hospitalized COVID-19 patients were promising, but randomized controlled studies were lacking at the time. The objective of this study was to investigate if convalescent plasma is beneficial to hospitalized patients with COVID-19. Results Hospitalized patients with confirmed COVID-19 and an oxygen saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to standard of care or standard of care only. The primary outcome was number of days of oxygen treatment to keep saturation above 93% within 28 days from inclusion. The study was prematurely terminated when thirty-one of 100 intended patients had been included. The median time of oxygen treatment among survivors was 11 days (IQR 6–15) for the convalescent plasma group and 7 days (IQR 5–9) for the standard of care group (p = 0.4, median difference -4). Two patients in the convalescent plasma group and three patients in the standard of care group died (p = 0.64, OR 0.49, 95% CI 0.08–2.79). Thus no significant differences were observed between the groups. Trial registration ClinicalTrials NCT04600440, retrospectively registered Oct 23, 2020.

Abstract Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

BackgroundBiologic disease-modifying drugs have revolutionised the treatment of a number of chronic inflammatory diseases (CID). However, up to 60% of the patients do not have a sufficient response to treatment and there is a need for optimization of treatment strategies.ObjectiveTo investigate if the treatment outcome of biological therapy is associated with the habitual dietary intake of fibre and red/processed meat in patients with a CID.MethodsIn this multicentre prospective cohort study, we consecutively enrolled 233 adult patients with a diagnosis of Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis (RA), Axial Spondyloarthritis, Psoriatic Arthritis and Psoriasis, for whom biologic therapy was planned, over a 3 year period. Patients with completed baseline food frequency questionnaires were stratified into a high fibre/low red and processed meat exposed group (HFLM) and an unexposed group (low fibre/high red and processed meat intake = LFHM). The primary outcome was the proportion of patients with a clinical response to biologic therapy after 14–16 weeks of treatment.ResultsOf the 193 patients included in our primary analysis, 114 (59%) had a clinical response to biologic therapy. In the HFLM group (N = 64), 41 (64%) patients responded to treatment compared to 73 (56%) in the LFHM group (N = 129), but the difference was not statistically significant (OR: 1.48, 0.72–3.05). For RA patients however, HFLM diet was associated with a more likely clinical response (82% vs. 35%; OR: 9.84, 1.35–71.56).ConclusionHabitual HFLM intake did not affect the clinical response to biological treatment across CIDs. HFLM diet in RA patients might be associated with better odds for responding to biological treatment, but this would need confirmation in a randomised trial.Trial registration(clinicaltrials.gov), identifier [NCT03173144].

Abstract In inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with pathophysiological changes in Crohn’s disease (CD) and ulcerative colitis (UC). Serum from IBD patients (CD: n = 65; UC: n = 107; irritable bowel syndrome: n = 18; healthy subjects: n = 20) was investigated in this study. The serological biomarkers C6Ma3 (a matrix metalloproteinase (MMP) generated fragment of the type VI collagen α3 chain) and PRO-C6, also called endotrophin (the C-terminus of the released C5 domain of the type VI collagen α3 chain) were measured by ELISAs. Serum C6Ma3 was increased in CD patients with moderate to severe and mild endoscopically active disease compared to endoscopic remission (p = 0.002, p = 0.0048), respectively, and could distinguish endoscopically active disease from remission with an AUC of 1.0 (sensitivity: 100%, specificity: 100%) (p

Abstract Background This report addresses how patients with hereditary hemorrhagic telangiectasia (HHT) and high output cardiac failure (HOCF) due to hepatic vascular malformations, should be evaluated and could be treated. HHT is a genetic disorder, leading to vascular abnormalities with potentially serious clinical implications. In the liver, arteriovenous malformations occur in more than 70% of patients, but only about 8% present clinical symptoms such as HOCF with pulmonary hypertension and less commonly portal hypertension, biliary ischemia and hepatic encephalopathy. Results Three female patients with HHT type 2 and HOCF caused by severe arteriovenous malformations in the liver are presented in this case series. The patients were seen at the HHT-Centre at Odense University Hospital. Treatment with either orthotopic liver transplantation (one patient) or bevacizumab (two patients) was initiated. All patients experienced marked symptom relief and objective improvement. New York Heart Association—class were improved, ascites, peripheral edema and hence diuretic treatment was markedly reduced or discontinued in all three patients. Bevacizumab also resulted in notable effects on epistaxis and anemia. Conclusion Our findings substantiate the importance of identification of symptomatic arteriovenous malformations in the liver in patients with HHT. Bevacizumab may possibly, as suggested in this case series and supported by previous case studies, postpone the time to orthotopic liver transplantation or even make it unnecessary. Bevacizumab represents a promising new treatment option, which should be investigated further in clinical trials.

Background and study aims Small bowel ulcerations are efficiently detected with deep learning techniques, whereas the ability to diagnose Crohnʼs disease (CD) in the colon with it is unknown. This study examined the ability of a deep learning framework to detect CD lesions with pan-enteric capsule endoscopy (CE) and classify lesions of different severity. Patients and methods CEs from patients with suspected or known CD were included in the analysis. Two experienced gastroenterologists classified anonymized images into normal mucosa, non-ulcerated inflammation, aphthous ulceration, ulcer, or fissure/extensive ulceration. An automated framework incorporating multiple ResNet-50 architectures was trained. To improve its robustness and ability to characterize lesions, image processing methods focused on texture enhancement were employed. Results A total of 7744 images from 38 patients with CD were collected (small bowel 4972, colon 2772) of which 2748 contained at least one ulceration (small bowel 1857, colon 891). With a patient-dependent split of images for training, validation, and testing, ulcerations were diagnosed with a sensitivity, specificity, and diagnostic accuracy of 95.7 % (CI 93.4–97.4), 99.8 % (CI 99.2–100), and 98.4 % (CI 97.6–99.0), respectively. The diagnostic accuracy was 98.5 % (CI 97.5–99.2) for the small bowel and 98.1 % (CI 96.3–99.2) for the colon. Ulcerations of different severities were classified with substantial agreement (κ = 0.72). Conclusions Our proposed framework is in excellent agreement with the clinical standard, and diagnostic accuracies are equally high for the small bowel and colon. Deep learning approaches have a great potential to help clinicians detect, localize, and determine the severity of CD with pan-enteric CE.

Abstract Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col‐16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col‐16 in serum may therefore have biomarker potential in GI disorders such as colorectal cancer (CRC) and ulcerative colitis (UC). The aim of this study was to determine whether col‐16 can serve as a biomarker for altered ECM remodeling in patients with CRC and UC. A monoclonal antibody was raised against the C‐terminal end of col‐16 (PRO‐C16), and a competitive enzyme‐linked immunosorbent assay (ELISA) was developed and technically validated. Levels of PRO‐C16 were measured in serum from patients with CRC (before (n = 50) and 3 months after (n = 23) tumor resections), UC (n = 39) and healthy controls (n = 50). The PRO‐C16 ELISA was specific toward the C‐terminal of col‐16. PRO‐C16 was significantly elevated both in serum from patients with CRC (P = 0.0026) and UC (P 0.999). Levels of PRO‐C16 identified patients with a GI disorder with a positive predictive value of 0.9 and an odds ratio of 12 (95%CI = 4.5‐29.5, P

Objective methods for examination of pouch function are warranted for a better understanding of the functional result and treatment of dysfunction. The objective of this study was to evaluate the results of scintigraphic intestinal transit time and defaecography compared to the results of pouch function, mucosal condition and a questionnaire on quality of life (QoL). This cross-sectional study included 21 patients. Scintigraphic transit time and defaecography was determined with the use of Tc-99m. Pouch function was assessed by number of bowel movements, pouch volume, and continence. Pouch mucosal condition was evaluated by endoscopy and histology. Median transit time was 189 min (105–365). Median ejection fraction at defaecography (EF) was 49% (3–77) and 62% (17–98) after first and second defecation. Median pouch volume was 223 mL (100–360). A median daily stool frequency of nine (4–25) was reported and three (14%) patients suffered from daytime incontinence. No patients had symptomatic or endoscopic pouchitis; however, the histology showed unspecific inflammation in 19 (90%) patients. There was no correlation between transit time, evacuation fraction (EF) and pouch function in univariate analysis. However, we found a high body mass index (BMI) and a low bowel movement frequency to be associated with a longer transit time by multivariate analysis. Scintigraphic determination of transit time and defaecography are feasible methods in patients with ileal pouch anal anastomosis, but the clinical relevance is yet doubtful.

Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD). However, the differences in extracellular matrix remodelling (ECM) in Crohn's disease (CD) and ulcerative colitis (UC) are not well described. An increased understanding of the inflammatory processes may provide optimized disease monitoring and diagnostics. We investigated the tissue remodelling in IBD and IBS patients by using novel blood-based biomarkers reflecting ECM remodelling.Five ECM biomarkers (VICM, BGM, EL-NE, C5M, Pro-C5) were measured by competitive ELISAs in serum from 72 CD patients, 60 UC patients, 22 patients with irritable bowel syndrome (IBS), and 24 healthy donors. One-way analysis of variance, Mann-Whitney U-test, logistic regression models, and receiver operator characteristics (ROC) curve analysis was carried out to evaluate the diagnostic accuracy of the biomarkers.The ECM remodelling was significantly different in UC compared to CD. The best biomarker combination to differentiate UC from CD and colonic CD was BGM and VICM (AUC = 0.98, P5mg/mL), correlation of Pro-C5 (r = 0.36) with CDAI was slightly improved compared to CRP (r = 0.27) corrected for the use of immunosuppressant. Furthermore, BGM and EL-NE biomarkers were highly associated with colon inflammation in CD patients.ECM fragments of tissue remodelling in IBD affect UC and CD differently, and may aid in differentiating IBD from IBS (EL-NE, BGM, Pro-C5), and UC from CD patients (BGM, VICM). Formation of type V collagen is related to the level of inflammation in CD and may reflect disease activity in CD.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that may cause severe bleeding complications with risk of perinatal death or lifelong disability. The main cause of FNAIT is maternal antibodies against human platelet antigen (HPA)-1a. Both fetomaternal bleeding and transplacental trafficking of fetal cells during pregnancy could be the cause of alloimmunization. Persistence of fetal cells in the mother (fetal microchimerism) and maternal cells in the child (maternal microchimerism) are well-recognized phenomena. Thus, it could be envisaged that fetal exposure to the HPA-1a antigen could tolerize an HPA-1a negative female fetus and prevent production of anti-HPA-1a antibodies later in life if she becomes pregnant with an HPA-1a positive fetus. The objective of the current study was to assess if the risk of producing anti-HPA-1a antibodies and the severity of neonatal thrombocytopenia in HPA-1a negative women with HPA-1a positive mothers (i.e. the mother is HPA-1a/b), was lower than in HPA-1a negative women with HPA-1a negative mothers. HPA-1a negative women with HPA-1a antibodies, identified from a Norwegian screening study (1996-2004), where HPA-1 genotype of their mothers was available, were included in the study. The frequency of HPA-1a positive mothers to HPA-1a immunized daughters were compared to the calculated frequency in the general population. We did not find any difference in the frequency of HPA-1ab among mothers to daughters with HPA-1a antibodies as compared with the general population. Furthermore, acknowledging sample-size limitations, we neither found an association between the mothers' HPA type and their daughters' anti-HPA-1a antibody levels or any difference between the two groups of mothers (HPA-1ab vs HPA-1bb), with respect to frequency of thrombocytopenia in the children of their daughters with HPA-1a antibodies. Hence, there was no indication of tolerance against fetal HPA-1a antigen in HPA-1bb women who had been exposed to HPA-1a antigen during fetal development.

Chronic inflammatory diseases (CIDs), including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.

Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT). In a study of 100, 448 pregnant women in Norway during 1995–2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25–0.75). Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side.

Background Neonatal alloimmune thrombocytopenia is most commonly due to transplacental passage of maternal anti-HPA 1a antibodies. A prospective study was carried out to evaluate the pattern and quantity of maternal anti-HPA 1a antibodies in order to predict the level of thrombocytopenia in the neonates.Design and Methods A monoclonal antibody immobilization of platelet antigen assay was used to detect antibodies in maternal samples from 1,990 HPA 1bb women. HLA DRB3*0101 typing was performed in all immunized women by sequencing the HLA DRB3 gene when present.Results Primary immunization more often took place in connection with delivery than during the first pregnancy. There was a strong correlation between maternal antibody levels and the platelet counts in the newborn (R2=0.49, p

Alloimmunization is a common phenomenon after transfusion, with an estimated incidence of 0.5% increasing to 20–60% in chronically transfused patients. In recently transfused patients, serological typing can be hampered by mixed field agglutination. We established RT-PCR methods for RHD, RHC/c and RHE/e typing using mRNA from reticulocytes. Molecular typing was performed soon after 51 separate mismatched transfusion events involving 30 patients. Accurate identification of the transfused patients’ phenotype was confirmed in all cases. Reticulocyte maturation studies revealed that temperature is a crucial parameter for transition into mature red blood cells.