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In this study, the investigators aim to identify novel targetable kinases in SR-a GvHD patient samples and investigate their role in different immune cell subtypes.
Corticosteroids are the first-line treatment of a GvHD, however many patients do not respond to corticosteroids. Patients with steroid-refractory a GvHD (SR-a GVHD) have a low 1-year survival rate. In this study, the investigators aim to identify and validate novel targetable kinases in SR-a GvHD patient peripheral blood mononuclear cells (PBMCs) by using a kinase-specific proteomic approach, and thereafter to investigate the role of the identified kinases in different immune cell subtypes by analyzing biopsies taken from SR- a GvHD patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Steroid-refractory a GvHD | Analysis of peripheral blood and intestinal biopsies of patients suffering from steroid-refractory a GvHD | ||
| Steroid-responsive a GvHD | Analysis of peripheral blood and intestinal biopsies of patients suffering from steroid-responsive a GvHD |
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| Measure | Description | Time Frame |
|---|---|---|
| Identification of differentially regulated kinases | Bead-based Kinase Assay enrichment (Knet beads) of PBMC lysates | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Analysis of protein expression | Analysis of PBMC lysates by western blot | 3 years |
| Analysis of immune cell subtype | Immunohistochemistry of intestinal biopsies |
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Inclusion Criteria:
Exclusion Criteria:
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Adult patients with acute GvHD, steroid-refractory or steroid-responsive
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| Name | Affiliation | Role |
|---|---|---|
| Robert Zeiser, Prof. Dr. | University Medical Center Freiburg | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26228813 | Background | Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lubbert M, Wasch R, Scheid C, Stolzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Graff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kroger N, Passweg J, Halter J, Socie G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct;29(10):2062-8. doi: 10.1038/leu.2015.212. Epub 2015 Jul 31. | |
| 29463561 |
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| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| 3 years |
| Background |
| Hulsdunker J, Ottmuller KJ, Neeff HP, Koyama M, Gao Z, Thomas OS, Follo M, Al-Ahmad A, Prinz G, Duquesne S, Dierbach H, Kirschnek S, Lammermann T, Blaser MJ, Fife BT, Blazar BR, Beilhack A, Hill GR, Hacker G, Zeiser R. Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset. Blood. 2018 Apr 19;131(16):1858-1869. doi: 10.1182/blood-2017-10-812891. Epub 2018 Feb 20. |
| 29171820 | Background | Zeiser R, Blazar BR. Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. N Engl J Med. 2017 Nov 30;377(22):2167-2179. doi: 10.1056/NEJMra1609337. No abstract available. |
| 24836575 | Background | Schwab L, Goroncy L, Palaniyandi S, Gautam S, Triantafyllopoulou A, Mocsai A, Reichardt W, Karlsson FJ, Radhakrishnan SV, Hanke K, Schmitt-Graeff A, Freudenberg M, von Loewenich FD, Wolf P, Leonhardt F, Baxan N, Pfeifer D, Schmah O, Schonle A, Martin SF, Mertelsmann R, Duyster J, Finke J, Prinz M, Henneke P, Hacker H, Hildebrandt GC, Hacker G, Zeiser R. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med. 2014 Jun;20(6):648-54. doi: 10.1038/nm.3517. Epub 2014 May 18. |