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Mucosal and Systemic Immune Profiles Differ During Early and Late Phases of the Disease in Patients With Active Ulcerative Colitis

Artikel i vetenskaplig tidskrift
Författare Georgios Mavroudis
Maria K Magnusson
Stefan Isaksson
Johanna Sundin
Magnus Simrén
Lena Öhman
Hans Strid
Publicerad i Journal of Crohns & Colitis
Volym 13
Nummer/häfte 11
Sidor 1450-1458
ISSN 1873-9946
Publiceringsår 2019
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor 1450-1458
Språk en
Länkar dx.doi.org/10.1093/ecco-jcc/jjz072
Ämnesord Inflammatory bowel disease, ulcerative colitis, gut immunology, inflammatory-bowel-disease, crohns-disease, t-helper, cytokine, cells, expression, il-1, th1, pathogenesis, maintenance, Gastroenterology & Hepatology
Ämneskategorier Gastroenterologi

Sammanfattning

Background and Aims: Alterations in the immunopathogenesis in ulcerative colitis [UC] during the disease course have been proposed. We therefore aimed to determine mucosal and systemic immune profiles in individual patients at the time of diagnosis [early disease] and after 10 years [late disease]. Methods: Patients with UC provided serum and mucosal biopsies during a flare in early and in late disease. Serum samples were analysed using the Olink Proseek Inflammation panel. mRNA gene expression of biopsies was analysed using the Qiagen RT2 Profiler PCR Arrays Antibacterial response and T Helper Cell Differentiation. Results: Orthogonal projections to latent structures discriminant analyses [OPLS-DA] demonstrated that the profile of 15 serum proteins discriminated in early and late disease [R2 = 0.84, Q2 = 0.65] in 15 UC patients. Eight of these proteins were differently expressed between the groups [Q <0.05]. Further, OPLS-DA of the mRNA profiles in biopsies strongly discriminated early and late disease with high predictability [R2 = 0.96, Q2 = 0.89]; 42 genes were differently expressed at the two time points [Q <0.05]. Finally, principal component analysis showed that T helper [Th] 1- and Th2-related genes were associated with early disease and late disease, respectively, and hierarchical cluster analysis was able to cluster patients with early from late disease with only minor overlap. Conclusions: Mucosal and systemic immune profiles differ between early and late disease in patients with active UC, with a transition from a Th1- to a Th2-driven disease in the intestine. Improved understanding of the variation in immunopathogenesis during the disease course in UC is important to guide individualised treatment decision making.

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