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- Mahajna, H., et al.
(author)
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Idiopathic Thrombocytopenic Purpura associated with Inflammatory Bowel Disease : a multi-centre ECCO CONFER case series
- 2022
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In: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 16:Suppl. 1, s. I561-I561
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Journal article (other academic/artistic)abstract
- Background: Idiopathic Thrombocytopenic Purpura (ITP) is an acquired haematological disorder with an incidence of 1 to 6 per 100.000, with reported comorbidity in patients with Inflammatory Bowel Disease (IBD). The current study aimed to evaluate the clinical presentation and outcome of ITP in IBD patients.Methods: This multicenter retrospective case series was performed as part of the ECCO Collaborative Network of Exceptionally Rare case reports (CONFER) project. Cases of patients with ITP and IBD were collected by participating investigators. Clinical data were recorded in a standardised collection form.Results: This report includes 20 patients with concurrent ITP and IBD: 15 were males, median age was 34 [Interquartile range (IQR) 25–56]. 12 subjects had a diagnosis of ulcerative colitis and 8 of Crohn’s disease. The diagnosis of IBD preceded the ITP diagnosis in 17 patients (median time between diagnosis was 7 years [IQR 1–14 years]). Among those, 10 patients were in IBD clinical remission at ITP diagnosis. Nine were treated with mesalamine, one with thiopurine, 4 with tumor necrosis factor-alpha (TNF) blockers, and 3 with no treatment. The mean platelet count at the presentation of ITP was 41.7±38.6 × 109/L. 6 patients had rectal bleeding, 8 had purpura, 6 had mucosal petechia, 2 had epistaxis, and 6 patients were asymptomatic. Regarding ITP treatment, 11 were treated with corticosteroids, 1 with Anti-RhD immunoglobulin, 7 with intravenous immunoglobulins (IVIG), 2 with rituximab and 2 patients eventually required splenectomy. All patients whose first presentation of ITP was rectal bleeding were treated medically with successful control of the ITP and IBD, None of them required splenectomy. 3 patients required colectomy with long-term follow-up, indicated by the IBD and not due to massive bleeding as a complication of ITP. With long-term follow-up, all patients had thrombocytes count above 50 × 109/L, and 18 were in IBD clinical remission.Conclusion: Most ITP cases in this case series occurred after the IBD diagnosis and responded well to regular ITP treatment. The course of the ITP in the IBD patients follows a regular course, including response to medical therapy and low rates of splenectomy.
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- Salomon, Benita, 1993-, et al.
(author)
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The serum protein profile across the IBD spectrum : Results from the COLLIBRI consortium
- 2024
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In: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I674-I676
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Journal article (other academic/artistic)abstract
- Background: Inflammatory bowel disease (IBD) is a heterogeneous disorder. Both subtypes, i.e., Crohn’s disease (CD) and ulcerative colitis (UC), differ in disease behaviour and inflamed gastrointestinal segments. Despite this, randomized controlled trials stratify patients based on CD and UC. Molecular characterization could uncover subtype-specific differences that could guide treatment and thereby overcome current therapeutic limitations. Therefore, we aimed to examine differences in serum inflammatory protein profiles across the IBD spectrum.Methods: This was a cross-sectional multicentre study of adult patients (≥18 years) with IBD from one Belgian and eight Swedish hospitals in the COLLIBRI consortium. IBD diagnosis and classification was based on international criteria, according to the Montreal classification. Relative serum protein levels were assessed using proximity extension assay technology (Olink Proteomics, Uppsala, Sweden; inflammation panel). We adopted smoothly clipped absolute deviation penalized logistic regression models to discriminate CD and UC patients. Using fitted CD vs UC logistic models, we estimated probability scores of CD vs UC for each patient based on their serum protein profiles. Scores ranged from 0 to 1, where lower scores indicated a higher molecular resemblance to UC. We evaluated the performance using leave-one-out cross-validation and the area under the curve (AUC).Results: Relative levels of 86 serum inflammatory proteins were available from 1,551 patients with IBD (CD, N=883; UC, N=639 and IBD-U, N=29) (Table 1). CD vs UC probability scores based on protein estimates for patients with UC, IBDU and different CD phenotypes (ileal CD, L1; colonic CD, L2; ileocolonic CD L3) are shown in Figure 1A. We observed a spectrum of IBD patients based on their CD vs CD probability scores with most pronounced differences between ileal CD and UC. Probability scores also differed significantly between colonic CD and ileal CD, but not between ileal and ileocolonic CD. The model performance to discriminate CD and UC yielded an AUC of 0.75. Restricting the samples to only one CD phenotype vs UC respectively resulted in the highest AUC for ileal CD (0.81), followed by ileocolonic CD (0.75) and colonic CD (0.65). Key proteins in the CD vs. UC model with higher protein estimates in UC were IL-17A, MMP10, FGF19. Contrary, CSF1, and SLAMF1, were higher in CD (Figure 1B).Conclusion: Our results on inflammation related serum proteins advocate for a more nuanced classification of CD into ileal-predominant and colonic-predominant subtypes. Such stratification could advance our understanding of IBD pathophysiology and may provide guidance for future therapeutic approaches.
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- Sudhakar, P., et al.
(author)
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Biomarkers for IBD using OLINK Proteomics inflammation panel : Preliminary results from the COLLIBRI consortium
- 2022
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In: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 16:Suppl. 1, s. I123-I124
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Journal article (other academic/artistic)abstract
- Background: Circulating serum proteins have provided insights into disease pathogenesis and are being used to identify prognostic, diagnostic and therapeutic biomarkers for chronic inflammatory diseases. With this pilot project, the Collaborative IBD Biomarker Research Initiative (COLLIBRI) consortium aimed to unravel disease heterogeneity in inflammatory bowel disease (IBD).Methods: Serum samples were cross-sectionally obtained from 3,390 indi -viduals (Crohn’s disease (CD), n=1815; ulcerative colitis (UC), n=1170;healthy, n=405) recruited at nine centres from Sweden and Belgium. Relative levels of 92 proteins were analysed using the Proseek Multiplex Inflammation I Probe kit 96x96 (Olink Proteomics, Uppsala, Sweden) and reported as arbitrary units, i.e., normalised protein expression on a log2 scale. Using a multivariate integrative approach, we identified protein signatures distinguishing CD and UC samples and attempted to identify clusters or subgroups within patients. Recruiting centre, cohort and batch information were considered for the integrative analysis. Optimisation was performed for identifying the number of components and features per component using 5-fold cross-validation and Leave-One-Group-Out-Cross-Validation, respectively. Information on transcriptional regulators was retrieved from the ReMap project using the orthogonal regulatory resource ChEA3.Results: A panel of 8 proteins was identified which could segregate CD and UC patients (Figure 1). FGF19 exhibited a consistent trend of expression (downregulated in CD) across all batches of datasets. An integrated AUC of 72.5% was achieved across the different batches of samples used in the study with the highest AUC (79.2%, P-value 8.5e-07) being recorded for a single batch of samples (CD = 42, UC = 56). On a centre-specific dataset, the cross-centre integrated signature achieved an AUC of 75.1%. We identified three transcription factors (MEF2A, BATF, NFKB2), of which the two latter ones are known to modulate intestinal inflammation and which could potentially regulate the expression of at least half of the genes encoding the proteins in the predictive 8-protein panel.Conclusion: We identified an integrated proteomic biomarker panel capable of separating CD and UC patients. Through further integration of confounder variables along with using other supervised and unsupervised approaches, subsequent analyses may further refine the molecul arheterogeneity among CD and UC patients. Our results demonstrate the need for large datasets to identify relevant clusters of patients with IBD, since the diagnosis exhibits a high degree of clinical heterogeneity.
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