Insufficient supply of organ for allotransplantation made the study on finding new organ resources from animal progress. Pig is regarded as one of the optimal donor animals for human. The major obstacle in this field is hyperacute reaction (HAR), which is triggered after the xenogenic natural antibodies preexisting in recipient blood combine to the antigens on the surface of the endothelium and activate the complement system. alpha-Galactose residues (alpha-Gal) on the endothelial cell have been identified as the major xenoantigens. NJZ Pig has been closely breed since 1938, whose family history is clear. Tissue samples from heart, liver, kidney, pancreas, lung, small intestine, skin, spleen, thymus and lymph node were obtained and embedded in paraffin. The sections were performed the immunohistochemical staining with the sera from health volunteers (including all the blood types) as the primary antibodies as well as the biotin labeled bandeirae simplicifolia I isolectin B4 (BS I-B4), which has specific affinity to alpha-galactose. All the staining sections were compared with the tissues digested with alpha-galactosidase. There was no difference between the antigens recognized by sera of different blood types. alpha-Gal was still the major xenoantigen on the endothelial cells. There might exist non-alpha-Gal antigens on the distal convoluted tubules and collecting tubules of the kidney. There was no alpha-Gal distributing on the secreting part of pancreas, either the islet cells or the matrix cells, but surely on pancreatic duct and vessels. All the antigenity was destroyed after the enzyme digestion except that the small intestine gland still positive with the BS I-B4. alpha-Gal is the major xenogenic antigen in NJZ Pigs. There exist some unknown antigens on the distal convoluted tubules and collecting ducts of the kidney. The blood type of recipient is not the first affair to be considered in pig-to-human xenotransplantation. The specificity of BS I-B4 for the alpha-galactose needs more detail research.
Limitation of donor source for allograft makes the research on xenograft progress. Pig is regarded as one of the ideal donor animals. The major obstacle in xenograft is hyperacute rejection, which is caused by complements after they are activated by xenogeneic antigens combined with natural antibodies. It has been confirmed that alpha-Gal is the major target antigen, whose expression is incharged by alpha-1,3 galactosyltransferase (alpha-GT). The approaches to overcome hyperacute rejection against alpha-Gal included: immunoadsorption of xenogeneic natural antibodies, lysis of antigen by enzyme and genetic manupilation to obtain animal lack of alpha-GT. Besides alpha-Gal, there were other antigens binding to human serum antibody, such as gp65 and gp100, which was expressed on PAEC after induced by TNF, the A-like antigen. But their function was still unknown. It was debatable on the role of MHC in xenograft. Both direct and indirect pathway were involved in cellular response in xenograft.
ObjectiveTo evaluate the effect of autoantibody on the efficacy and safety of pegylated interferonα-2a (Peg-IFNα-2a) and ribavirin on chronic hepatitis C (HCV). MethodsWe enrolled 106 chronic HCV infected patients, who were divided into autoantibody-positive group and negative group based on the baseline autoantibody detection. The patients were treated for 48 weeks. The anti-viral response and adverse effects were observed. Data analyses were reported using the SPSS 20.0 statistical package. ResultsThe prevalence of any autoantibody in chronic hepatitis C patients amounted to 31.1%, and serum anti-nuclear antibody was positive in 24 patients. Difference in age, sex, serum alanine transaminase level, aspartate transaminase level, total bilirubin level, thyroid function and HCV RNA level between autoantibody-positive group and negative group was not significant (P > 0.05). The level of hemoglobin in autoantibody-positive group was significantly lower than the negative group (P=0.018). Of the 106 patients, 82 patients achieved sustained virological response (SVR), 56 achieved rapid virological response (RVR), 98 achieved ealy virological response (EVR) and 8 were non-responders. There were no significant differences between RVR, EVR and SVR in autoantibody-positive group and negative group (P > 0.05). The most common adverse effects in this study were fatigue, weight loss, hair loss and fever, and no significant differences in adverse effects were observed between the two groups (P > 0.05). ConclusionAutoantibody positivity may not affect the treatment response and is safe in chronic HCV infected patients with combination therapy of pegylated interferonα-2a plus ribavirin.
ObjectiveTo explore the clinical features of myasthenia gravis (MG) harboring both acetylcholine receptor antibody (AChRAb) and muscle-specific tyrosine kinase antibody (MuSKAb) positivity.MethodsWe searched PubMed, Web of Science, Embase and China National Knowledge Infrastructure databases (from inception to November 2016), to collect the case reports of MG with both AChRAb and MuSKAb positivity. Along with one case discovered in Department of Neurology, West China Hospital, the clinical data of the cases were retrospectively analyzed.ResultsA total of 13 double-seropositive MG patients were enrolled in this study, demonstrating a marked female predominance (including 1 male and 12 females) and a younger age at onset [(31.07±24.77) years]. During the disease course, 10 of the included patients presented severe bulbar involvement, dyspnea and neck weakness, with myasthenic crisis in 6 individuals. Among the 11 patients with detailed records, abnormal thymus glands comprised 4 thymus hyperplasia and one thymoma. While the response to oral pyridostigmine was unsatisfactory in 11 double-seropositive MG patients, ranging from mild benefit to overt intolerance; the patients treated with plasma exchange (3/3), rituximab (1/1) or corticosteroid (7/12) improved dramatically, with other immumosuppressants and intravenous immunoglobulin partially responsive. Moreover, 5 patients undergoing thymectomy improved markedly or partially.ConclusionsCompared with MG patients with MuSKAb positivity merely, the condition of the double-seropositive MG patients seem to be more severe and further inclined to myasthenic crisis. The incidence of abnormal thymus, such as thymus hyperplasia, is higher. Thymectomy may be an effective treatment for such patients.
【Abstract】ObjectiveTo study the specific cytotoxicity of amygdalin(a new prodrug) to LoVo cells in antibody directed enzyme prodrug therapy (ADEPT). MethodsThe specific activation of amygdalin by anti-CEA McAb-β-glucosidase conjugate and the cytotoxicity of amygdalin to LoVo cells were assessed throughTrypan blue exclusion. ResultsThe cytotoxicity of amygdalin itself to LoVo cells was low. However, when amygdalin was combinated with anti-CEA McAb-β-glucosidase conjugate, its cytotoxic effect was enhanced by nearly 40 times, and that effect was specific to to LoVo cells expressing CEA . When LoVo cells and MCF-7 cells were co-cultured in various ratios, the cytotoxic effect of amygdalin combinated with anti-CEA McAb-β-glucosidase conjugate was measured. The survival rate of cultured cells decreased while the percentage of LoVo cells increased, suggesting the cytotoxic effect to be specific to LoVo cells. ConclusionThe toxicity of amygdalin is low，and it can be activated by anti-CEA McAb-β-glucosidase conjugate effectively to kill targetd cells specifically which may be a new way for colorectal tumor therapy.
ObjectiveTo investigate the effects of thyroid globulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) statuses on central lymph node (CLN) metastasis in patients with differentiated thyroid cancer (DTC).MethodsA retrospective analysis was performed on 526 patients with DTC confirmed by pathology from nine participating institutions, who underwent the bilateral thyroidectomy plus bilateral CLN dissection. The clinicopathologic characteristics of different TGAb and TPOAb statuses of patients with DTC were compared, and whether the TGAb and TPOAb statuses were the independent risk factors of CLN metastasis in DTC patients or not was analyzed.ResultsAll of 526 patients with DTC were included in this study, 152 were males and 374 were females. The age was (44±11) years old. There were 63 cases of TgAb＋TPOAb＋, 60 cases of TgAb＋TPOAb－, 30 cases of TgAb－TPOAb＋, and 373 cases of TgAb－TPOAb－. It was found that there was a significant difference in the gender among the four different antibody statuses of patients, that was, women with abnormal antibodies were more common (P<0.001), not found that there were related to the tumor size, blood vessel invasion, nerve invasion, CLN metastasis, tumor multifocality, and bilateral tumor or not (P>0.050). In this study, there were 389 cases of CLN with metastasis and 137 cases of CLN without metastasis. The results of multivariate analysis found that the age and gender of the patients were the independent risk factors (P<0.001), but didn’t find the TgAb and TPOAb Statuses and other factors were related to the CLN metastasis (P>0.050).ConclusionsStatuses of TGAb and TPOAb aren’t obviously associated with CLN metastasis in patients with DTC, which is inconsistent with other studies. It needs to be further researched after expanding existing sample size and determining new predictive factors.
Synthesized Rb peptide was used as an antigen to immunize the BALB/C mice. After fusing and screening with ELISA and Western Blot, we got 3 hybridomas which secreted specific monoclonal antibodies against product of Rb gene. All of three kinds of antibodies were fourld to be IgG 1 through the appraisement. In addition,since we mixed three kinds of peptides as the antigens to immunize the mice,we have got three different hinds of monoclonal antibodies including one against Rb product and another two in the Same procedure. （Chin J Ocul Fundus Dis,1993,9:2-4）
Objective To explore clinical features and risk factors of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with pulmonary involvement. Methods A retrospectively study of clinical data of 113 AAV patients with pulmonary involvement was conducted in the First Affiliated Hospital of Soochow University from January 2015 to December 2020. The differences in general characteristics, treatment and prognosis of different types of AAV with pulmonary involvement were compared. In addition, the clinical characteristics and survival status between the pulmonary involvement group and the non-pulmonary involvement group (n=69) were analyzed. Multivariate logistic regression model was used to analyze the risk factors. Results A total of 113 patients (57 males and 56 females) of AAV with pulmonary involvement were enrolled, including 86 cases of microscopic polyangiitis (MPA), 21 cases of granulomatosis polyangiitis (GPA), 6 cases of eosinophilia granulomatosis (EGPA). The average age was (67±11) years old. There was no significant difference in the age and gender distribution. The clinical manifestations were non-specific. Interstitial lung disease was common imaging feature of MPA, multiple nodules or mass was common in GPA, the incidence of sinusitis in EGPA was significantly higher (P<0.05). Seventy-three patients were complicated with extrapulmonary involvement. The most common organ involved was the kidney, followed by the cardiovascular and nervous system. The most important organs involved in MPA, EGPA and GPA were kidney, heart, and ear, nose, throat respectively. Compared with the non-pulmonary involvement group, the proportions of Birmingham vasculitis activity score (BVAS) ≥15 points, higher antineutrophil cytoplasmic antibody titer and lower complement C3 or C4, pulmonary infection, mechanical ventilation and plasmapheresis in the pulmonary involvement group were significantly higher (P<0.05). Forty patients died during the follow-up. One-year cumulative survival was further calculated using the Kaplan-Meier method, which demonstrated that pulmonary involvement was a risk factor for higher mortality in AAV patients. Compared with the survival group, the proportions of coronary heart disease, multiple organs involvement (n≥3), BVAS≥15 points, serum creatinine≥500 μmol/L, hemoglobin≤90 g/L, C-reactive protein≥10 mg/L, pulmonary infection, requiring mechanical ventilation, continuous renal replacement therapy and plasmapheresis in the death group were significantly higher (P<0.05). Conclusions AAV with pulmonary involvement is more common in the elderly, the morbidity is similar between male and female, and the clinical manifestations are usually non-specific. The chest imaging manifestations are mainly pulmonary interstitial changes, multiple nodules and masses. Multiple organs involvement occurs more often. BVAS≥15 points is independent risk factor for pulmonary involvement in AAV patients. The prognosis of AAV patients with pulmonary involvement is relatively poor. Combined with coronary heart disease, pulmonary infection and CRP≥10 mg/L are independent risk factors of poor prognosis.
【Abstract】Objective To investigate the potential role of tumor necrosis factoralpha (TNFα) in apoptosis after combined liver and kidney transplantation in rats. MethodsEighty rats which had combined liver and kidney transplantation were randomly paired, were divided into study group (n=20) and control group (n=20). 40 ml of 4 ℃ sodium chloride and antiTNFα monoclonal antibody (30 ml was infused from portal veins to donated livers and 10 ml from renal arteries to donated kidneys) were infused to the study group (0.1 mg/kg weight),and the same quantity of 4 ℃ sodium chloride was infused the control group. Venous blood was drew at different phases after the transplantations to detect the function of kidney and liver. The level of TNFα and the cell apoptosis were detected in the transplanted tissues of liver and kidney by ELISA and terminal deoxynucleotidy transferase mediated dTUPbiotin nickend labeling (TUNEL). ResultsThe levels of AST, ACT, Cr and BUN in the study group were significantly lower than those of the control group at the same phases (P＜0.05). The level of TNFα in the transplanted tissues of kidney and liver was also significantly lower as compared with those of control group. The cell apoptosis index of the transplanted tissues of kidney and liver was significantly smaller in the study group （P＜0.05）. There was no dramatically pathological change in the tissues of transplanted kidney and liver, which were treated with antiTNFα monoclonal antibody, and the structures are almost normal. ConclusionAntiTNFα monoclonal antibody may reduce cell apoptosis and accelerate the restoration of function of liver and kidney after combined liver and kidney transplantation.