Interleukin-22 levels are increased in gastrointestinal graft-<i>versus</i>-host disease in children

Lounder, Dana T.; Khandelwal, Pooja; Gloude, Nicholas J.; Dandoy, Christopher E.; Jodele, Sonata; Medvedovic, Mario; Denson, Lee A.; Lane, Adam; Lake, Kelly E; Litts, Bridget; Wilkey, Alyss; Davies, Stella M.

doi:10.3324/haematol.2017.174771

Cited by 7 publications

(3 citation statements)

References 13 publications

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“…In this context, the upregulation of IL22 appears to compensate or counter-regulate ongoing inflammation as already seen for Foxp3 (21), IDO (22) and GPR (23) in gastric or colonic biopsies of GvHD patients. A previous study by Lounder and colleagues analyzed serum IL-22 in pediatric SCT patients and showed an association with higher serum IL-22 with subsequent GI-GvHD but not with the incidence of TRM (24). In contrast, we found a significant reduction of intestinal IL22 in patients with subsequent TRM.…”

Section: Discussioncontrasting

confidence: 61%

Low Intestinal IL22 Associates With Increased Transplant-Related Mortality After Allogeneic Stem Cell Transplantation

et al. 2022

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The role of IL-22 in adult patients undergoing allogeneic stem cell transplantation (SCT) is of major interest since animal studies showed a protective and regenerative effect of IL-22 in graft versus host disease (GvHD). However, no clinical data exist on the tissue expression. Here we demonstrate that patients not suffering from transplant-related mortality (TRM) show significantly upregulated IL22 expression during histological and clinical GI-GvHD (p = 0.048 and p = 0.022, respectively). In contrast, in GvHD patients suffering from TRM, IL22 was significantly lower (p = 0.007). Accordingly, lower IL22 was associated with a higher probability of TRM in survival analysis (p = 0.005). In a multivariable competing risk Cox regression analysis, low IL22 was identified as an independent risk factor for TRM (p = 0.007, hazard ratio 2.72, 95% CI 1.32 to 5.61). The expression of IL22 seemed to be microbiota dependent as broad-spectrum antibiotics significantly diminished IL22 expression (p = 0.019). Furthermore, IL22 expression significantly correlated with G-protein coupled receptor (GPR)43 (r = 0.263, p = 0.015) and GPR41 expression (r = 0.284, p = 0.009). In conclusion, our findings reveal an essential role of IL-22 for the prognosis of patients undergoing allogeneic SCT.

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Section: Discussioncontrasting

confidence: 61%

Low Intestinal IL22 Associates With Increased Transplant-Related Mortality After Allogeneic Stem Cell Transplantation

et al. 2022

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“…To evaluate plasma biomarkers of GVHD, in addition to IL6R as described above, samples were analyzed using ELISAs for regenerating family member 3 alpha (REG3A) (MBL Cat#5323/5310) [ 26 – 28 ]: REG3A is an anti-microbial peptides (AMP) and has been identified and validated as a diagnostic biomarker of gastrointestinal (GI) GVHD [ 24 , 29 ]. Plasma REG3A plasma concentrations have been reported to be higher in GI GVHD patients [ 24 , 30 ].…”

Section: Methodsmentioning

confidence: 99%

Evaluating immune response and metabolic related biomarkers pre-allogenic hematopoietic stem cell transplant in acute myeloid leukemia

et al. 2022

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Although hematopoietic stem cell transplantation (HCT) is the only curative treatment for acute myeloid leukemia (AML), it is associated with significant treatment related morbidity and mortality. There is great need for predictive biomarkers associated with overall survival (OS) and clinical outcomes. We hypothesized that circulating metabolic, inflammatory, and immune molecules have potential as predictive biomarkers for AML patients who receive HCT treatment. This retrospective study was designed with an exploratory approach to comprehensively characterize immune, inflammatory, and metabolomic biomarkers. We identified patients with AML who underwent HCT and had existing baseline plasma samples. Using those samples (n = 34), we studied 65 blood based metabolomic and 61 immune/inflammatory related biomarkers, comparing patients with either long-term OS (≥ 3 years) or short-term OS (OS ≤ 1 years). We also compared the immune/inflammatory response and metabolomic biomarkers in younger vs. older AML patients (≤30 years vs. ≥ 55 years old). In addition, the biomarker profiles were analyzed for their association with clinical outcomes, namely OS, chronic graft versus host disease (cGVHD), acute graft versus host disease (aGVHD), infection and relapse. Several baseline biomarkers were elevated in older versus younger patients, and baseline levels were lower for three markers (IL13, SAA, CRP) in patients with OS ≥ 3 years. We also identified immune/inflammatory response markers associated with aGVHD (IL-9, Eotaxin-3), cGVHD (Flt-1), infection (D-dimer), or relapse (IL-17D, bFGF, Eotaxin-3). Evaluation of metabolic markers demonstrated higher baseline levels of medium- and long-chain acylcarnitines (AC) in older patients, association with aGVHD (lactate, long-chain AC), and cGVHD (medium-chain AC). These differentially expressed profiles merit further evaluation as predictive biomarkers.

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“…During aGVHD, Brüggen et al observed an increase in IL-22 messenger RNA and IL-22-producing CD4 + T cells in the skin (98). Similarly, Lounder et al reported that higher plasma IL-22 level is positively correlated with the incidence of Gut-GVHD in children (99). In cGVHD, on the other hand, Gartlan et al showed that donor CD4 + T cell-derived IL-22 significantly exacerbated cutaneous cGVHD, and high levels of both IL-17A and IL-22 expressions were present in the skin of cGVHD patients (100).…”

Section: Dual Role Of Il-22 In Promoting Tissue Regeneration and Infl...mentioning

confidence: 96%

Steroid-Refractory Gut Graft-Versus-Host Disease: What We Have Learned From Basic Immunology and Experimental Mouse Model

2022

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Intestinal graft-versus-host disease (Gut-GVHD) is one of the major causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). While systemic glucocorticoids (GCs) comprise the first-line treatment option, the response rate for GCs varies from 30% to 50%. The prognosis for patients with steroid-refractory acute Gut-GVHD (SR-Gut-aGVHD) remains dismal. The mechanisms underlying steroid resistance are unclear, and apart from ruxolitinib, there are no approved treatments for SR-Gut-aGVHD. In this review, we provide an overview of the current biological understanding of experimental SR-Gut-aGVHD pathogenesis, the advanced technology that can be applied to the human SR-Gut-aGVHD studies, and the potential novel therapeutic options for patients with SR-Gut-aGVHD.

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Interleukin-22 levels are increased in gastrointestinal graft-versus-host disease in children

Cited by 7 publications

References 13 publications

Low Intestinal IL22 Associates With Increased Transplant-Related Mortality After Allogeneic Stem Cell Transplantation

Low Intestinal IL22 Associates With Increased Transplant-Related Mortality After Allogeneic Stem Cell Transplantation

Evaluating immune response and metabolic related biomarkers pre-allogenic hematopoietic stem cell transplant in acute myeloid leukemia

Steroid-Refractory Gut Graft-Versus-Host Disease: What We Have Learned From Basic Immunology and Experimental Mouse Model

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