Study On The Risk Factors And Diagnostic Biomarkers Of Chronic Graft-versus-host Disease

BackgroundAllogeneic hematopoietic stem cell transplantation(allo-HSCT)is an effective treatment for malignant and nonmalignant hematological diseases.The survival rate of patients with hematopoietic stem cell transplantation is significantly higher than before due to the optimization of transplantation scheme and the progress of supportive treatment.Chronic graft-versus-host disease(cGVHD)is the main factor that influences long-term survival and nonrecurrent death(NRD)in patients after allogeneic hematopoietic stem cell transplantation.It can affect multiple target organs,cause different degrees of damage,and even lead to disability,affecting the quality of patients'life extremely.The clinical manifestations of cGVHD are complex,similar to autoimmune disease.The pathogenesis is not clear,the main pathophysiological process is inflammatory response,the common pathological response is fibrosis.It is usually characterized by limited or extensive multiple organs involved,including skin,eyes,digestive tract,eyes,liver,lung,genital tract,fascia,joint,lymphopoietic system,etc.The diagnosis of cGVHD dominatly depends on clinical symptoms,pathological examination and 2014 National Institutes of health(NIH)diagnostic criteria.In the course of cGVHD,there is no specific manifestations and effective diagnostic methods,especially when the symptoms overlap with acute graft-versus-host disease(aGVHD).It would effectively improve the survival rate and quality of patients' life if cGVHD can be diagnosed and treated timely.Therefore,it is significant to search for specific biomarkers for the diagnosis of cGVHD.ObjectiveTo explore the risk factors of cGVHD,and to provide references for early prediction of cGVHD.To screen out the potential valuable biomarkers for the diagnosis of cGVHD,and to provide a theoretical basis for the diagnosis of cGVHD.MethodWe selected 112 patients with allo-HSCT from the Hematology Department of the First Affiliated Hospital of Zhengzhou University from January 2015 to October 2019,collected clinical data and blood samples.According to the occurrence of cGVHD,the patients were divided into two groups:69 patients in cGVHD group,18 patients in non cGVHD group,and 25 patients who lost or relapsed.Another 18 healthy control group were recruited.We analyzed the influence of age,gender,diagnosis,gender of the donor,type of the donor,HLA site consistency,preconditioning regimen and other factors on the occurrence of cGVHD.The expression levels of SGK1,Rock2,CCL15,TGF? and IL17 in the three groups were detected by enzyme-linked immunosorbent assay(ELISA),and the differences between the three groups were analyzed.Result1.Among the 112 patients,69 had cGVHD,the incidence was 61.6%,and among them,32 patients had moderate cGVHD(46.38%)and 20 patients had aGVHD(28.99%).The most involved organs of cGVHD were skin,liver,mucosa,digestive tract,lung,blood system and joint.2.The mean age of cGVHD group was 35.35 ± 11.02,the mean age of cGVHD group was 26.22 ± 5.725,the difference was statistically significant(P<0.05);the incidence of cGVHD in HLA matched patients was 69.57%(32/46),lower than that of HLA non-identical patients 90.24%(37/41),the difference was statistically significant(P<0.05).There was no significant difference in other factors such as gender,diagnosis,donor gender and type,preconditioning regimen(P>0.05).3.The expression of SGK1 and Rock2 in cGVHD group was significantly higher than that in non cGVHD group(P<0.05),and was higher in multiple organ affected patients than single organ affected patients(P<0.05).There was no difference in the expression of Rock2 and SGK1 in different target organs(P>0.05).The expression of Rock2 protein was high in severe cGVHD(P<0.05).4.The survival time of severe cGVHD patients was shorter than that of mild and moderate cGVHD patients(P<0.05).Age,HLA locus,SGK1 protein concentration and Rock2 protein concentration had no significant effect on the survival time(P>0.05).