CD4+ immune response as a potential biomarker of patient reported inflammatory bowel disease (IBD) activity

Brandhorst, Gunnar; Weigand, Sebastian; Eberle, Christoph; Roggenbuck, Dirk; Karaus, M.; Oellerich, Michael; Walson, Philip D.

doi:10.1016/j.cca.2013.02.016

Cited by 11 publications

(9 citation statements)

References 25 publications

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“…Inflammatory bowel diseases (IBDs) are a collection of chronic inflammatory disorders of the gastrointestinal tract in human and animals. The major symptoms are visceral hypersensitivity (VH) (visceral pain, altered bowel movement, increased mucosal secretion) with weight loss, malnutrition, fever and lack of appetite [ 1 , 2 ]. VH is one of the important symptoms in about 50–70 % of patients experiencing the initial onset of IBD.…”

Section: Introductionmentioning

confidence: 99%

A novel model for studying ileitis-induced visceral hypersensitivity in goats

et al. 2015

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BackgroundVisceral hypersensitivity (VH) is a common condition in many gastrointestinal disorders such as inflammatory bowel diseases (IBDs) in human and animals. Most studies often induce Crohn’s disease/colitis to investigate VH in small experimental animals. Although farm animals commonly suffer from IBDs, their VH has not been investigated so far. Because goats can suffer from Johne’s disease, a naturally occurring Crohn’s-like disease, they may be suitable to be used for studying the mechanism underlying VH in common intestinal disorders of large animals. In the present study, 60 healthy goats of either sex were equally divided into a 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) group and saline group. A volume of 1.2 ml of TNBS-ethanol solution (30 mg TNBS in 40 % ethanol) or an equal volume of isotonic saline was injected into the wall of the terminal ileum through laparotomy. The severity of the developing ileitis was determined according to macro- and microscopic pathologic scores and the levels of myeloperoxidase, interleukin-1β, interleukin-6 and tumor necrosis factor-α, and VH was evaluated with visceromotor responses (VMR) to colorectal distension on days 3, 7, 14, 21 and 28. VMRs were assessed with a continuous ramp distention mode with 6 s for each pressure (20, 40, 60, 80 and 100 mmHg).ResultsCompared to the saline group, the TNBS-treated goats showed apparent transmural pathological changes and a significant increase (P < 0.05) in macroscopic and microscopic change scores, and levels of myeloperoxidase, interleukin-1β, interleukin-6 and tumor necrosis factor-α in the ileum, and VMR to colorectal distension. The goats exhibited apparent ileitis at days 3 to 21, and VH at days 7 to 28 following TNBS treatment.ConclusionThis experiment successfully established a reproducible ileitis and VH with administration of TNBS-ethanol solution in the ileal wall of goats. This model is useful for studying the pathogenesis of the IBD and the mechanism underlying VH, and for evaluating the efficacy of new therapeutic regimens.

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Section: Introductionmentioning

confidence: 99%

A novel model for studying ileitis-induced visceral hypersensitivity in goats

et al. 2015

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“…The antitumor effect and reactivity against alloantigen could be used as surrogate markers for retention of overall host immune function (32). Here, the recipient T cells from the KaAPCs group and PBS group presented comparable proliferation levels in response to the SPCs from naïve BALB/c mice (Figures S9A,B in Supplementary Material), suggesting that the native T cell repertoires of recipient mice retained the third-party reactivity after KaAPCs treatment.…”

Section: Resultsmentioning

confidence: 99%

An Antigen-Presenting and Apoptosis-Inducing Polymer Microparticle Prolongs Alloskin Graft Survival by Selectively and Markedly Depleting Alloreactive CD8+ T Cells

Wang

Shahzad

et al. 2017

Front. Immunol.

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Selectively depleting the pathogenic T cells is a fundamental strategy for the treatment of allograft rejection and autoimmune disease since it retains the overall immune function of host. The concept of killer artificial antigen-presenting cells (KaAPCs) has been developed by co-coupling peptide–major histocompatibility complex (pMHC) multimer and anti-Fas monoclonal antibody (mAb) onto the polymeric microparticles (MPs) to induce the apoptosis of antigen-specific T cells. But little information is available about its in vivo therapeutic potential and mechanism. In this study, polyethylenimine (PEI)-coated poly lactic-co-glycolic acid microparticle (PLGA MP) was fabricated as a cell-sized scaffold to covalently co-couple H-2Kb-Ig dimer and anti-Fas mAb for the generation of alloantigen-presenting and apoptosis-inducing MPs. Intravenous infusions of the biodegradable KaAPCs prolonged the alloskin graft survival for 43 days in a single MHC-mismatched murine model, depleted the most of H-2Kb-alloreactive CD8+ T cells in peripheral blood, spleen, and alloskin graft in an antigen-specific manner and anti-Fas-dependent fashion. The cell-sized KaAPCs circulated throughout vasculature into liver, kidney, spleen, lymph nodes, lung, and heart, but few ones into local allograft at early stage, with a retention time up to 36 h in vivo. They colocalized with CD8+ T cells in secondary lymphoid organs while few ones contacted with CD4+ T cells, B cells, macrophage, and dendritic cells, or internalized by phagocytes. Importantly, the KaAPC treatment did not significantly impair the native T cell repertoire or non-pathogenic immune cells, did not obviously suppress the overall immune function of host, and did not lead to visible organ toxicity. Our results strongly document the high potential of PLGA MP-based KaAPCs as a novel antigen-specific immunotherapy for allograft rejection and autoimmune disorder. The in vivo mechanism of alloinhibition, tissue distribution, and biosafety were also initially characterized, which will facilitate its translational studies from bench to bedside.

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“…(17) Recent studies evaluating the use of cell-mediated immune function assay in non-transplant patient population like inflammatory bowel disease and rheumatoid arthritis are emerging. (18) (19) Although the immune assay did not show any correlation with disease activity, it was helpful in identifying patients at increased risk of infection in these studies. Specifically, the immune assay level was significantly lower in patients with infection when compared to patients without.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of cell-mediated immune function in risk stratification for patients with advanced heart failure

Nagarajan

Hernandez

Cauthen

et al. 2017

American Heart Journal

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Background Although heightened inflammation and autoimmune responses have been well-described in patients with heart failure, the role of cell-mediated immune function in the pathogenesis and progression of heart failure is unclear. The aim of our study is to evaluate the prognostic role of cell-mediated immune function in patients with advanced heart failure. Methods We studied patients with advanced heart failure referred for evaluation of candidacy for advanced heart failure therapies between 2007 and 2010. Cell-mediated immune response was categorized into three groups – low or poor immune response (≤ 225 ng/ml), moderate or normal immune response (226 – 524 ng/ml) and strong immune response (≥ 525ng/ml) using a phytohemagglutinin-stimulated T-cell response assay. Results Out of 368 patients, 41 patients (11.1%) had poor immune function, 258 patients (70.1%) had normal immune function, and 69 patients (18.7%) had strong immune function. The primary outcome of all-cause mortality or cardiac transplantation occurred in 63.4%, 45.3% and 34.8% in the poor immunity, normal immunity and strong immune function groups, respectively. In univariate analysis, cell-mediated immune function was strongly associated with the primary outcome (p=0.014). Poor immune function portended worse prognosis (Hazard ratio=2.18, 95%CI 1.01–4.70, p=0.047) and strong immune function was associated with better survival (Hazard ratio = 0.67, 95% CI 0.43–1.04). However, when adjusted for multiple variables in multivariate analysis, immune function status lost its overall significance to predict primary outcome (p=0.11), but the direction to an increased risk of primary outcome was maintained in the poor immune function group. Conclusion Poor cell-mediated immune function measured by a clinically available assay could be associated with more adverse long-term prognosis in patients with advanced heart failure.

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CD4+ immune response as a potential biomarker of patient reported inflammatory bowel disease (IBD) activity

Cited by 11 publications

References 25 publications

A novel model for studying ileitis-induced visceral hypersensitivity in goats

A novel model for studying ileitis-induced visceral hypersensitivity in goats

An Antigen-Presenting and Apoptosis-Inducing Polymer Microparticle Prolongs Alloskin Graft Survival by Selectively and Markedly Depleting Alloreactive CD8+ T Cells

Usefulness of cell-mediated immune function in risk stratification for patients with advanced heart failure

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