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001-es BibID:BIBFORM077046
035-os BibID:(WoS)000485146200010 (Scopus)85070584761
Első szerző:Deutschmann, Claudia
Cím:Identification of Chitinase-3-like protein 1 as a novel neutrophil antigenic target in Crohn's disease / Deutschmann Claudia, Sowa Mandy, Murugaiyan Jayaseelan, Roesler Uwe, Röber Nadja, Conrad Karsten, Laass Martin, Bogdanos Dimitrios, Sipeki Nora, Papp Maria, Rödiger Stefan, Roggenbuck Dirk, Schierack Peter
Dátum:2019
ISSN:1873-9946
Megjegyzések:Background and Aims: There is an increasing incidence of inflammatory bowel disease [IBD]. Autoimmune responses are involved in the pathophysiology of IBD, but their underlying pathways and target antigens have not yet been fully elucidated. Methods: Autoantigenic targets in IBD were identified after separation of whole cell proteins isolated from neutrophils using two-dimensional electrophoresis and matrix assisted laser desorption ionization - time of flight mass spectrometry-based protein identification of the spots that displayed Western blotting signals with anti-neutrophil cytoplasmic antibody-positive sera. The prevalence of IgG, IgA and secretory IgA [sIgA] to chitinase 3-like protein 1 [CHI3L1] was analysed by enzyme-linked immunosorbent assays using recombinant CHI3L1 in 110 patients with Crohn's disease [CD], 95 with ulcerative colitis [UC], 126 with coeliac disease [CeD] and 86 healthy controls [HCs]. Results: The 18-glycosylhydrolase family member CHI3L1 was identified as a neutrophil autoantigenic target. CD patients displayed significantly higher levels of IgG to CHI3L1 than patients with UC and CeD (p < 0.0001, respectively). IgA and sIgA to CHI3L1 was significantly higher in CD than in UC, CeD and HCs [p < 0.0001, respectively]. IgA and sIgA to CHI3L1 demonstrated the highest prevalence in CD [25.5%, 28/110; and 41.8%%, 46/110] compared to HCs [2.3%, 2/86; and 4.7%%, 4/86; p < 0.0001, respectively] and are associated with a more complicated progression of CD. Conclusion: CHI3L1 is a novel neutrophil autoantigenic target in CD. IgA and sIgA to CHI3L1 may serve as novel markers for CD and may facilitate the serological diagnosis of IBD.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
inflammatory bowel disease
chitinase-3 like protein 1
autoantibody
Crohn's disease
enzyme-linked immunosorbent assay
Megjelenés:Journal of Crohns & Colitis. - 13 : 7 (2019), p. 894-904. -
További szerzők:Sowa, Mandy Murugaiyan, Jayaseelan Roesler, Uwe Röber, Nadja Conrad, Karsten Laass, Martin Bogdanos, Dimitrios P. Sipeki Nóra (1987-) (általános orvos) Papp Mária (1975-) (belgyógyász, gasztroenterológus) Rödiger, Stefan Roggenbuck, Dirk Schierack, Peter
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2.

001-es BibID:BIBFORM083946
Első szerző:Lopens, Steffi
Cím:The search for the Holy Grail : autoantigenic targets in primary sclerosing cholangitis associated with disease phenotype and neoplasia / Steffi Lopens, Marcin Krawczyk, Maria Papp, Piotr Milkiewicz, Peter Schierack, Yudong Liu, Ewa Wunsch, Karsten Conrad, Dirk Roggenbuck
Dátum:2020
ISSN:2038-0305 2038-3274
Megjegyzések:Unlike in other autoimmune liver diseases such as autoimmune hepatitis and primary biliary cholangitis, the role and nature of autoantigenic targets in primary sclerosing cholangitis (PSC), a progressive chronic immune-mediated, life threatening, genetically predisposed, cholestatic liver illness, is poorly elucidated. Although anti-neutrophil cytoplasmic antibodies (ANCA) have been associated with the occurrence of PSC, their corresponding target(s) have not yet been identified entirely. Genome wide association studies recently revealed a significant number of immune-related and even disease-modifying susceptibility loci for PSC. However, they did not allow to discern a clear autoimmune pattern nor do therapy options and male gender preponderance in PSC support a pathogenic role of autoimmune responses. Yet, there is growing evidence that PSC is closely linked to the co-occurrence of inflammatory bowel disease (IBD) phenotypes. The identification of novel autoantigenic targets interacting with the gut microbiota in IBD such as the major zymogen granule membrane glycoprotein 2 (GP2) or the detection of high-sensitive proteinase 3 (PR3) autoantibodies have refocused the interest on a putative association of loss of tolerance with the IBD phenotype. Not surprisingly, the report of GP2 IgA to be associated with fibrosis in PSC and disease severity gave new impetus to autoantibody research for autoimmune liver illnesses and might usher in a new era of serological research in this field. The mucosal loss of tolerance against the microbiota-sensing GP2 modulating innate and adaptive intestinal immunity and its putative role in the pathogenesis of PSC will be discussed along with other potential PSC-related autoantigenic targets such as the neutrophil PR3 in this review. GP2 IgA may represent a group of new pathogenic antibodies which share characteristics of both type 2 and 3 of antibody-mediated hypersensitive reactions according to Coombs and Gell.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
primary sclerosing cholangitis
microbiota
ulcerative colitis
Crohn's disease
inflammatory bowel disease
cirrhosis
cholangiocarcinoma
immunoglobulin A
Megjelenés:Autoimmunity Highlights. - 11 : 1 (2020), p. 1-14. -
További szerzők:Krawczyk, Marcin Papp Mária (1975-) (belgyógyász, gasztroenterológus) Milkiewicz, Piotr Schierack, Peter Liu, Yudong Wunsch, Ewa Conrad, Karsten Roggenbuck, Dirk
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3.

001-es BibID:BIBFORM115819
Első szerző:Sipeki Nóra (általános orvos)
Cím:Location-based prediction model for Crohn's disease regarding a novel serological marker, anti-chitinase 3-like 1 autoantibodies / Nora Sipeki, Patricia Juliannna Kovats, Claudia Deutschmann, Peter Schierack, Dirk Roggenbuck, Maria Papp
Dátum:2023
ISSN:1007-9327
Megjegyzések:Abstract BACKGROUND Defective neutrophil regulation in inflammatory bowel disease (IBD) is thought to play an important role in the onset or manifestation of IBD, as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens. Like neutrophils in the context of innate immune responses, immunoglobulin A (IgA) as an acquired immune response partakes in the defense of the intestinal epithelium. Under normal conditions, IgA contributes to the elimination of microbes, but in connection with the loss of tolerance to chitinase 3-like 1 (CHI3L1) in IBD, IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms. The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target, the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear. AIM To determine the predictive potential of Ig subtypes of a novel serological marker, anti-CHI3L1 autoantibodies (aCHI3L1) in determining the disease phenotype, therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients. METHODS Sera of 257 Crohn's disease (CD) and 180 ulcerative colitis (UC) patients from a tertiary IBD referral center of Hungary (Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen) were assayed for IgG, IgA, and secretory IgA (sIgA) type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1, along with 86 healthy controls (HCONT). RESULTS The IgA type was more prevalent in CD than in UC (29.2% vs 11.1%) or HCONT (2.83%; P < 0.0001 for both). However, sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT (39.3% and 32.8% vs 4.65%, respectively; P < 0.0001). The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement (P < 0.0001 and P = 0.038, respectively) in patients with CD. Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity (57.1% vs 36.0%, P = 0.009). IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group (46.9% vs 25.7%, P = 0.005). In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis, positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models. This association disappeared after merging subgroups of different disease locations. CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD. The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Chitinase 3-like 1 autoantibodies
Crohn's disease
Ulcerative colitis
Disease progression
Immunoglobulin subtypes
Enzyme-linked immunosorbent assay
Megjelenés:World Journal of Gastroenterology. - 29 : 42 (2023), p. 5728-5750. -
További szerzők:Kováts Patrícia (1995-) Deutschmann, Claudia Schierack, Peter Roggenbuck, Dirk Papp Mária (1975-) (belgyógyász, gasztroenterológus)
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4.

001-es BibID:BIBFORM074575
035-os BibID:(cikkazonosító)1959 (WoS)000442936400001 (Scopus)85068120394
Első szerző:Sowa, Mandy
Cím:Mucosal autoimmunity to cell-bound GP2 isoforms is a sensitive marker in PSC and associated with the clinical phenotype / Mandy Sowa, Rafał Kolenda, Daniel Baumgart, Johann Pratschke, Maria Papp, Tamas Tornai, Jaroslaw Suchanski, Dimitrios Bogdanos, Maria Mytilinaiou, Jutta Hammermann, Martin Laass, Karsten Conrad, Christoph Schramm, Andre Franke, Dirk Roggenbuck, Peter Schierack
Dátum:2018
ISSN:1664-3224
Megjegyzések:Introduction: Zymogen granule glycoprotein 2 (GP2) was demonstrated as first autoimmune mucosal target in primary sclerosing cholangitis (PSC) associated with disease severity. Autoantibodies to four GP2 isoforms (aGP21-4) were found in patients with inflammatory bowel diseases but reactivity against specific GP2 epitopes has not been investigated in PSC yet. Hence, the prevalence of aGP21-4 and their association with the PSC phenotype for risk prediction were examined.Methods: GP2 isoforms were stably expressed as glycosylphosphatidylinositol- anchored molecules in the membrane of HEp-2-cells and used as autoantigenic targets in indirect immunofluorescence assay (IFA). aGP21-4 IgA and IgG were detected by IFA in 212 PSC patients of four European university hospitals and 145 controls comprising 95 patients with cystic fibrosis and 50 healthy subjects.Results: Combined aGP21 and aGP24 IgA testing with a sensitivity of 66.0% and a specificity of 97.9% resulted in the best diagnostic performance (Youden index: 0.64) regarding all aGP2 and combinations thereof. aGP24 IgA positivity is significantly associated with the presence of cirrhosis in PSC (p=0.0056). Logistic regression revealed the occurrence of aGP21 IgA (odds ratio [OR] 1.38, 95% confidence interval [CI]: 1.03-1.86) and aGP24 IgA (OR 1.52, 95%CI: 1.07-2.15) along with male gender (OR 0.51, 95%CI: 0.27-0.97) and older age (OR 1.03 95%CI: 1.01-1.05) as significant risks for the concomitant presence of cirrhosis in PSC.Conclusions: Combined aGP21 and aGP24 IgA analysis is preferred to single aGP2 isoform analysis for sensitive PSC autoantibody testing. Positivity for aGP21 and aGP24 IgA is associated with cirrhosis in PSC and could be used for risk stratification.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
zymogen granule glycoprotein 2
primary sclerosing cholangitis
cirrhosis
cholangiocarcinoma
immunoglobulin A
Megjelenés:Frontiers in Immunology. - 9 (2018), p. 1-10. -
További szerzők:Kolenda, Rafał Baumgart, Daniel Pratschke, Johann Papp Mária (1975-) (belgyógyász, gasztroenterológus) Tornai Tamás István (1984-) (belgyógyász) Suchanski, Jaroslaw Bogdanos, Dimitrios P. Mytilinaiou, Maria Hammermann, Jutta Laass, Martin Conrad, Karsten Schramm, Christoph Franke, Andre Roggenbuck, Dirk Schierack, Peter
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