抗HLA和抗MICA抗体的表达对移植肾功能和急性排斥反应的预示作用

Objective To investigate the prediction of anti-human leukocyte antigen antibodies (HLA) and anti-major histocompatibility complex class I-related chain A antibodies (MICA) to the development of acute rejection (AR) and kidney allograft function. Methods Forty-one kidney transplant patients were prospectively tested for anti-HLA and anti-MICA. Thirty-seven patients were screened using Luminex/single-antigen beads to determine the HLA and MICA-specific antibody levels at 0,30,90, 180,360,720 and 1080 days post-transplantation. The patients and donors of HLA and MICA allele typing were determined by PCR-SSOP, and donor specific antibody (DSA) and non-donor specific antibody (NDSA) were identified.Simultaneously,their serum creatinine (SCr) levels and clinical data were analyzed. Results Nine patients (21.95 % ,9/41 ) had pre-existing anti-HLA and(or) anti-MICA, including 6 cases of anti-MICA,2 cases of anti-HLA, and one case of anti-MICA and anti-HLA. Nine patients had pre-existing DSA and NDSA. In the 37 patients, 6 patients (16.2% ) developed de novo anti-HLA, and 3 (8.1%) developed de novo antiMICA. In patients positive for de novo anti-HLA, the titer of antibody was gradually increased during the follow-up of three years. Four patients out of 9 patients with pre-existing antibodies were suffered from AR (44.4%); In 6 patients positive for de novo anti-HLA,three cases (50.0%) were suffered from AR; In three patients positive for de novo anti-MICA,no AR occurred (P＜0.05). In two patients positive for DSA of HLAⅡ antibody detected at the third and seventh day after transplantation, the renal grafts were renovecd due to rejection. The Scr levels in patients positive for pre-existing MICA with AR were higher than in those positive for pre-existing MICA without AR at each scheduled time point during the follow-up period (P＜0.05). The Scr levels in patients negative for antibodies pre-transplantation and having AR were higher than in those having no AR at each scheduled time point during the follow-up period (P＜0. 01 ). The Scr levels in patients positive for de novo HLA and MICA and having AR one month following transplantation were higher than in those negative for antibodies and having no AR (P＜0.01 ). Conclusion Pre-existing and de novo anti-HLA were the irnportant factors for the development of AR, but the mismatch of HLA and MICA alleles in donors and patients was primary causes for generation of de novo antibodies.     

致敏肾移植受者抗MICA抗体的表达对术后早期排斥反应和肾功能的影响

Objective To explore the expression of anti-MICA antibodies and evaluate its influence on acute rejection and renal function in early period after renal transplantation. Methods A total of 29 sensitized subjects (PRA＞20 %) were enrolled in this study. All the patients underwent protein A immunoabsorption treatment and the expression of anti-MICA antibodies was detected before and after treatment. Triple immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil (MMF) and steroid was given to prevent graft rejection. The correlation between the expression of anti-MICA antibodies and acute rejection or serum creatinine (SCr) level was analyzed.Results The expression of anti-MICA antibodies was detected in 8 candidates (27. 6 % ,8/29) ,and 6 kinds of anti-MICA antibodies simultaneously expressed were found in one individual, 3 kinds in one case,and sole kind in 6 patients. There was no significant difference in acute rejection rate between positive anti-MICA antibodies group and negative group [37.5 % (3/8) vs 38. 1% (8/21), P＞0.05). The positive expression rate of anti-MICA antibodies in the recipients with PRA ≥40% was higher than that in those with PRA ＜40% [43. 8 % (7/16) vs 7. 7 % (1/13),P＜0.05]. The SCr level in patients positive for anti-MICA antibodies was markedly higher than that in those negative anti-MICA antibodies at the 1st week postoperatively ( 135.4 ± 21.4 vs 108. 6 -+ 31.6 μmol/L, P＜0.05). The SCr level in the patients with positive anti-MICA antibodies, however, was reduced to the normal range at the 2nd week after surgery (P＞0.05). The levels of anti-MICA antibodies were continuously decreased in the candidates undergoing protein A irnmunoadsorption treatment. Conclusion Higher expression of anti-MICA antibodies exists in sensitized recipients and possesses an influence on the recovery of renal function in early postoperative period. Protein A immunoadsorption can eliminate anti-MICA antibodies effectively in sensitized recipients.     

致敏肾移植受者抗MICA抗体的表达对术后早期排斥反应和肾功能的影响

Objective To explore the expression of anti-MICA antibodies and evaluate its influence on acute rejection and renal function in early period after renal transplantation. Methods A total of 29 sensitized subjects (PRA＞20 %) were enrolled in this study. All the patients underwent protein A immunoabsorption treatment and the expression of anti-MICA antibodies was detected before and after treatment. Triple immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil (MMF) and steroid was given to prevent graft rejection. The correlation between the expression of anti-MICA antibodies and acute rejection or serum creatinine (SCr) level was analyzed.Results The expression of anti-MICA antibodies was detected in 8 candidates (27. 6 % ,8/29) ,and 6 kinds of anti-MICA antibodies simultaneously expressed were found in one individual, 3 kinds in one case,and sole kind in 6 patients. There was no significant difference in acute rejection rate between positive anti-MICA antibodies group and negative group [37.5 % (3/8) vs 38. 1% (8/21), P＞0.05). The positive expression rate of anti-MICA antibodies in the recipients with PRA ≥40% was higher than that in those with PRA ＜40% [43. 8 % (7/16) vs 7. 7 % (1/13),P＜0.05]. The SCr level in patients positive for anti-MICA antibodies was markedly higher than that in those negative anti-MICA antibodies at the 1st week postoperatively ( 135.4 ± 21.4 vs 108. 6 -+ 31.6 μmol/L, P＜0.05). The SCr level in the patients with positive anti-MICA antibodies, however, was reduced to the normal range at the 2nd week after surgery (P＞0.05). The levels of anti-MICA antibodies were continuously decreased in the candidates undergoing protein A irnmunoadsorption treatment. Conclusion Higher expression of anti-MICA antibodies exists in sensitized recipients and possesses an influence on the recovery of renal function in early postoperative period. Protein A immunoadsorption can eliminate anti-MICA antibodies effectively in sensitized recipients.     

肾移植术后血清抗MICA抗体与慢性排斥反应的相关性

Objective To explore the relationship of serum anti-MICA antibody and development of chronic rejection (CR) after renal transplantation. Methods The enrolled 105 patients included 43 cases of CR, and 62 cases of functioning renal allograft as controls. Data including PRA level before transplantation, HLA mismatch, cold ischemic time, SCr at discharge, immunosuppressive regimen,and months after transplantation were analyzed. Blood samples were collected immediately after grouping for anti-MICA antibodies, SCr determination. Acute rejection episodes and renal allograft function which was evaluated by △SCr/M [(SCr at present - SCr at discharge) /months after transplantation) were compared between anti-MICA-antibody positive patients and anti-MICA-antibody negative patients. Results There was no significant difference in gender, age, HLA mismatch, cold ischemic time, immunosuppressive regimen, SCr at discharge, months after transplantation between CR and control groups (P＞0.05). Serum creatinine level and number of antiMICA-antibody positive patients in CR group were significantly increased as compared with those in control group (P＜0.01 ). Acute rejection episodes during the first 3 months after transplantation in anti-MICA-antibody positive patients were significantly more than those in anti-MICA-antibody negative patients (P＜0.05),and the △SCr/M in the former was higher than that in the latter (8.3 +3.6 vs 2.4 ± 2.6, P＜0.05). Conclusion Humoral immunoreaction mediated by MICA partly participates the development of CR after renal transplantation. MICA antibody is a risk factor affecting long-term allograft function.     

肾移植术后血清抗MICA抗体与慢性排斥反应的相关性

Objective To explore the relationship of serum anti-MICA antibody and development of chronic rejection (CR) after renal transplantation. Methods The enrolled 105 patients included 43 cases of CR, and 62 cases of functioning renal allograft as controls. Data including PRA level before transplantation, HLA mismatch, cold ischemic time, SCr at discharge, immunosuppressive regimen,and months after transplantation were analyzed. Blood samples were collected immediately after grouping for anti-MICA antibodies, SCr determination. Acute rejection episodes and renal allograft function which was evaluated by △SCr/M [(SCr at present - SCr at discharge) /months after transplantation) were compared between anti-MICA-antibody positive patients and anti-MICA-antibody negative patients. Results There was no significant difference in gender, age, HLA mismatch, cold ischemic time, immunosuppressive regimen, SCr at discharge, months after transplantation between CR and control groups (P＞0.05). Serum creatinine level and number of antiMICA-antibody positive patients in CR group were significantly increased as compared with those in control group (P＜0.01 ). Acute rejection episodes during the first 3 months after transplantation in anti-MICA-antibody positive patients were significantly more than those in anti-MICA-antibody negative patients (P＜0.05),and the △SCr/M in the former was higher than that in the latter (8.3 +3.6 vs 2.4 ± 2.6, P＜0.05). Conclusion Humoral immunoreaction mediated by MICA partly participates the development of CR after renal transplantation. MICA antibody is a risk factor affecting long-term allograft function.     

肾移植术后监测受者抗HLA抗体的临床意义

目的 监测肾移植受者术后抗HLA抗体水平,探讨新生的抗HLA抗体对移植肾功能的影响.方法 共有384例肾移植受者术后进行了抗HLA抗体的监测,监测时间3～96个月,所有受者术前的抗HLA抗体水平均为阴性.使用莱姆德抗原板,采用酶联免疫吸附法(ELISA)检测抗HLA抗体,抗HLA抗体水平＞10%为阳性.对术后抗HLA抗体阳性者与阴性者间移植肾功能进行比较,观察新生抗HLA抗体对移植肾功能的影响.结果 术后抗HLA抗体阴性者318例(82.8%);阳性者66例(17.2%),其中抗HLA Ⅰ类抗体阳性者3例,抗HLAⅡ类抗体阳性者61例,抗HLA Ⅰ类和Ⅱ类抗体均为阳性者2例.HLA-DR位点0个抗原错配者92例受者中有7例新生抗HLA抗体,1～2个抗原错配者292例中有59例新生抗HLA抗体,二者比较,差异有统计学意义(P＜0.01).术后抗HLA抗体阴性者中移植肾功能良好者占87.4%(278/318),抗HLA抗体阳性者中移植肾功能良好者占65.2%(43/66),二者比较,差异有统计学意义(P＜0.05).结论 HLADR位点的抗原错配与肾移植后抗HLA抗体的产生密切相关,而新生抗HLA抗体会造成移植肾功能下降,从而降低移植存活率,肾移植术后监测抗HLA抗体有一定的临床意义.

Abstract：

Objective To detect de novo development of anti-HLA antibodies after renal transplantation, and to investigate their influence on graft function. Methods 384 kidney recipients,who were negative for anti-HLA antibody before transplantation, were monitored for anti-HLA antibodies over a period of 3-96 months, and a sensitive enzyme-linked immunosorbent assay (ELISA) was used to detect anti-HLA antibodies. HLA antibody ＞10 % was defined as positive levels. Results Among 384 recipients tested, 318 recipients (82. 8 %) were negative for anti-HLA antibody after transplantation; 66 recipients (17. 2 %) developed de novo HLA antibodies, 3 recipients with HLA class Ⅰ, 61 with HLA class Ⅱ, 2 with both HLA class Ⅰ and Ⅱ. According to amino acid residue matching, 7 cases developed de novo antibodies among 92 recipients with 0 HLA-DR mismatches,compared with 59 cases among 292 recipients with 1-2 mismatches, which showed significant difference between two groups (P＜0. 01 ). 87. 4 % (278/318) recipients negative for HLA antibodies after transplantation achieved good graft function, in comparison with 65. 2 % (43/66) recipients positive for HLA antibodies (P＜0. 05). Conclusion De novo production of HLA antibodies posttransplantation may be closely associated with HLA-DR mismatch. De novo HLA antibodies posttransplantation might damage graft function and reduce graft survival rate. The detection of de novo development of anti-HLA antibodies after renal transplantation has clinical significance for assessing renal allograft function.     

下肢动脉缺血性患者假性高压的鉴别及临床意义

Objective To evaluate the diagnosis of and management for pseudo-high blood pressure in patients with lower limb ischemia. Methods From March 2006 to March 2007, 182 cases with lower limb ischemia were admitted, and they were divided into three groups. In group 1 pseudo-high blood pressure did not exist, in group 2, patients had pseudo-high blood pressure with ABI<1.3, in group 3, patients had pseudo-high blood pressure and with ABI≥1.3. ABI and TBI were compared with color Doppler, angiography, MRA and CTA. Results In all those 182 patients, there were 102(56.0%)cases having no pseudo-high blood pressure, and 27.5% with concomitant diabetes. Seventy-two cases(39.6%) had pseudo-high blood pressure (ABI<1.3) with 44.4% having diabetes. Eight cases (4.4%) (ABI≥ 1.3) manifested pseudo-high blood pressure with the ratio concomitant diabetes being 75%. Conclusions In diabetic patients with lower limb's ischemia there is increased ratio of pseudo-high blood pressure.     

肾移植患者术前输血与再次移植致抗体生成的比较

Objective To compare the incidence of HLA antibody production between transfusion and second renal transplant ation.Methods A total of 1810 patients were tested panel reactive antibody(PRA,April.2002-December 2006)before renal transplant,509 patients experienced 200 mL blood transfusion,185 males,324 females;136 patients experienced second renal transplant ation,93 males,43 females.PRA was screened using HLA-Ⅰ and HLA-Ⅱ antigen tray(One lanmbda;GTI),PRA type was identified using One lanmbda LAT-1240.Result 509 patients experienced transfusion,88 patients showed PRA positive (17.28%),4.32%male,12.97%female.136 second renal transplant ation patients,97 showed PRA positive(71.32%),male 50.0%,female 21.32%.Transfusion caused higher PRA incidence.High incidence HLA-Ⅰ antibodies were A1,A2,A3,A11,A24;B13,B27,B60,B22,B51,B17.No high incidence HLA-Ⅱ antibody werefound.High incidence HLA-Ⅰ and Ⅱ antibodies were A2,A11,A24;B13,135,B40 and DRI,DR4,DR7,DR8,DR15 in second renal transplant patients.Conclusion The incidence of PRA production was higher in second renal transplant patients than that in blood transfusion patients,what's more,HLA antibody intensity and type were much more complicated,that's why second transplant caused rejection more easily.     

膝关节骨关节炎滑液和软骨骨桥蛋白水平与其病变程度的相关性

Objective To examine osteopontin (OPN) levels in both synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and to investigate their relationship with severity of the disease. Methods Fifty patients with knee OA and 10 healthy controls were enrolled in this study.There were 15 males and 35 females with an average age of 61.8±7.4 years in OA group. The control group included 4 males and 6 females with an average age of 63.2±6.0 years. Mankin score were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed using the Kellgren-Lawrence criteria. OPN levels in synovial fluid were measured using enzyme-linked immunosorbent assay. OPN levels in articular cartilage were assessed by immunohistochemical methods. Results Compared to healthy controls, the knee OA patients had higher OPN concentration in synovial fluid ([4519.60±1830.37] pg/ml vs. [1179.70±303.39] pg/ml) and articular cartilage([0.60±0.06] vs. [0.43 ±0.07]). In addition, synovial fluid OPN levels showed a positive correlation with articular cartilage OPN levels (r=0.411,P=0.003). Subsequent analysis showed that the OPN levels in synovial fluid significantly had been correlated with severity of disease using Kellgren-Lawrence criteria (r=0.581, P＜ 0.001). Furthermore,the levels of OPN in the articular cartilage also were correlated with disease severity using Mankin score (r=0.675, P＜ 0.001).Conclusion The data suggest that OPN in synovial fluid and articular cartilage is related to progressive joint damage and could be a predictive biomarker respect to disease severity and progression in knee OA.     

膝关节骨关节炎滑液和软骨骨桥蛋白水平与其病变程度的相关性

Objective To examine osteopontin (OPN) levels in both synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and to investigate their relationship with severity of the disease. Methods Fifty patients with knee OA and 10 healthy controls were enrolled in this study.There were 15 males and 35 females with an average age of 61.8±7.4 years in OA group. The control group included 4 males and 6 females with an average age of 63.2±6.0 years. Mankin score were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed using the Kellgren-Lawrence criteria. OPN levels in synovial fluid were measured using enzyme-linked immunosorbent assay. OPN levels in articular cartilage were assessed by immunohistochemical methods. Results Compared to healthy controls, the knee OA patients had higher OPN concentration in synovial fluid ([4519.60±1830.37] pg/ml vs. [1179.70±303.39] pg/ml) and articular cartilage([0.60±0.06] vs. [0.43 ±0.07]). In addition, synovial fluid OPN levels showed a positive correlation with articular cartilage OPN levels (r=0.411,P=0.003). Subsequent analysis showed that the OPN levels in synovial fluid significantly had been correlated with severity of disease using Kellgren-Lawrence criteria (r=0.581, P＜ 0.001). Furthermore,the levels of OPN in the articular cartilage also were correlated with disease severity using Mankin score (r=0.675, P＜ 0.001).Conclusion The data suggest that OPN in synovial fluid and articular cartilage is related to progressive joint damage and could be a predictive biomarker respect to disease severity and progression in knee OA.     

Rheoencephalography and the study of the pulsation of the cervical vascular network in the diagnosis of goiter and neck and mediastinal tumors

The authors have applied rheography of the brain and sphygmography of the vessels of the neck and mediastinum for the diagnosis of compression of the neck vessels and organs in goiter and tumors of retrosternal and deep cervical localization. The methods allow to recognize stenosing of the vessels in early stages and facilitate the diagnosis of these conditions.     

Ocular immunopathological characteristics and the involvement of the platelet-aggregation factor and the anti-PAF at the level of the eye

This lecture tries to systematize the data about PAF (platelet activating factor) complex implications in the different ocular immune responses, and about the therapeutical results of PAF antagonists ?n experimental and clinical inflammatory conditions.     

Relation between the structure of the annulus fibrosus and the function and failure of the intervertebral disc

A simple model is presented that explains the observed function and failure of the intervertebral disc in compression, torsion, and bending; this model is based upon the observed arrangement of collagenous fibers in the annulus fibrosus. The fibers are considered to have the same mechanical properties as tendon; thus the stresses required to produce a given deformation and which irreversibly damage the fibers can be predicted. Predictions of the mechanical behavior of the disc are in good agreement with published results for compression and torsion; no comparable experiments have been performed for bending. It is further predicted that torsion and bending are likely to cause annular failure and protrusion. Failure is likely to occur posteriorly because of the effect of forward bending and because in the flattened and reentrant discs of the lumbar spine, torsional stress is concentrated at the points of maximum curvature. The structure of the disc tends to protect the collagenous fibers in forward bending and torsion. Compression is predicted to cause end-plate fracture rather than annular failure.