| BACKGROUNDPrevious studies on the relationship between autoantibody profile andprogression of primary biliary cirrhosis remain unknown. In addition, circulating andhepatic T cells are often involved in the development of primary biliary cirrhosis,skewed frequency as well as the ratio of T cells may lead to proliferation ofautoreactive of T cells and immune disorder in PBC patients, but the relationshipbetween T cells of PBC patients and the clinical markers are elusive. Currently,ursodeoxycholic acid (UDCA) is the only approved first-line drug for PBC patients.Response to UDCA treatment in PBC patients can effectively slow down the diseaseprogression and prolong survival duration, however, more than40%of the patientsare with incomplete response to UDCA therapy. At present, novel effective regimenfor the incomplete response patients is urgently necessary.AIM1. To investigate the correlation between autoantibody profile and the clinicalmanifestation as well as the progression of PBC patients.2. Analyze the change of T cells subsets between PBC and HC and furtherdetect the relationship between the changes and the clinical marker. The changes of Tcells subsets in different stage of cirrhosis PBC patients should also be examined.3. To conduct a preliminary study on the safety and efficacy of UC-MSCstransfusion in7PBC patients with incomplete response to UDCA.METHODS1. Peripheral autoantibodies (ANA, AMA) such as AMA-M2, anti-PML, anti-gp210, anti-Sp100, anti-BPO, anti-Ro-52in123PBC patients were detected byindirect immunofluorescence assay and Western blot. The clinical data, laboratoryparameters, type-B ultrasonic and imaging results of patients were also checked.2. Flow cytometry were performed to analyze the frequency changes ofperipheral T cells in49PBC patients.3. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) transfused to7PBC patients with an incomplete response to UDCA and observed the evaluation forthe safety and efficacy of UC-MSCs treatment.RESULTS1. Expression of ANA、AMA、AMA-M2、anti-PML、anti-SP100、anti-52KDhad no significant statistically differences between two groups of PBC patients. Theanti-gp210positive patients were significantly higher in cirrhosis PBC patients thanin non-cirrhosis groups. The serum level of aminotransferase, bilirubin and alkalinephosphatase were significantly higher and the serum level of cholinesterase andalbumin levels were lower in anti-gp210positive patients than in negative patients.2. Compared with HC, the frequencies of peripheral CD4+T cells, the ratio ofCD4/CD8were significantly increased and the frequencies of peripheral CD8+Tcells were significantly decreased in PBC patients. Further studies revealed thatCD4/CD8T-cell ratio were significantly higher in PBC patients in decompensatedstage than in compensated stage; peripheral frequency of CD8+T cell hadsignificantly positive correlation with ALB, CHE, PA, while a significant negativecorrelation with the PT and INR; CD4/CD8ratio had significant positive correlationwith PT and INR but had significant negative correlation with ALB, PA and CHE.Frequency of Th1cells were positively correlated with CHE, the number ofautoantibodies and negative correlated with TBA, PT and INR. Frequency of Th17cell subsets had positive correlation with number of autoantibodies and negativelycorrelated with ALB and ALB/GLO.3. No obvious recent and long-termed side-effects were found in the patientstreated with UC-MSCs. There was a significant decrease in serum alkaline phosphatase levels in patients transfused with UC-MSCs. The Mayo risk score, aprognostic index, was also stable during the treatment and follow-up period.Transfusion of UC-MSCs could also improved the quality of life of patients withPBC, reduced fatigue and skin itching. In some patients the liver function andclinical symptoms were also improved.CONCLUSIONS：1. We found that compared with anti-gp210negative patients, anti-gp210positive patients exhibit severe cholestasis and impaired liver function, anti-gp210might represent a predictive marker for the progression of PBC.2. Peripheral frequencies of CD8+T cells significantly decreased in patientswith PBC, especially in decompensated stage patients, thus contributing to theprogression of PBC. In addition, elevated peripheral frequencies of CD4+T cells arelikely to indirectly undermine the synthetic function of the liver. Th17cells maynegatively affect the protein synthesis function in patients with PBC.3. UC-MSCs transfusion is well tolerated in PBC patients who respond onlypartially to UDCA treatment,... |
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