Effects of Double Filtration Plasmapheresis on Nocturnal Respiratory Function in Myasthenic Patients

Assessment of respiratory function using combined oximetry‐cutaneous capnography has never been evaluated in patients with myasthenia gravis (MG). We investigated the effects of double filtration plasmapheresis (DFPP) on respiratory status in 18 MG patients. Results of combined oximetry and transcutaneous capnography, MG scores, and acetylcholine receptor antibody titers before and after DFPP treatment were compared. The respiratory monitoring was performed at three time periods (morning, afternoon, and sleep). Mean MG score was markedly lower after DFPP treatment (5.7) than before treatment (7.9). Before DFPP, the minimum pulse oximetric saturation (SpO₂) level obtained during the night session was significantly lower (P = 0.0513 and P = 0.0199) than the levels obtained during the two daytime sessions. A similar phenomenon was noted for maximum transcutaneous carbon dioxide tension (PtcCO₂). After DFPP treatment, the maximum and mean PtcCO₂ levels were significantly higher (P = 0.0056) in the morning than in the afternoon. Of all the respiratory function parameters measured, only minimum SpO₂ levels obtained during morning sessions before DFP treatment differed significantly from those obtained after DFPP treatment (P = 0.0322). Overall, however, minimum SpO₂ levels as well as mean and maximum PtcCO₂ levels improved significantly during sleep after DFPP. In conclusion, we found that respiratory function abnormalities were common in myasthenic patients without clinical respiratory symptoms. DFPP treatment resulted in minimal improvement of respiratory parameters.     

Plasmapheresis Does Not Affect Polysomnographic Parameters in Patients With Myasthenia Gravis: A Case Series Study

The purpose of this study was to evaluate the influence of plasmapheresis on sleep in patients with generalized myasthenia gravis and no respiratory symptoms. Seven myasthenia gravis patients, four women and three men, aged 24–52 years, underwent plasmapheresis treatment because of recent worsening of clinical weakness and poor response to previous treatments. We prospectively recorded the myasthenia gravis score, measured acetylcholine‐receptor antibody concentration, performed polysomnography, and checked the Epworth Sleepiness Scale at baseline and 1 day after completion of the last session of plasmapheresis. Myasthenic weakness was ameliorated following plasmapheresis in all patients with a median decrease in myasthenia gravis score of 2 points (P = 0.0002) and a median clearance of 43.3% of acetylcholine‐receptor antibody. However, there was no significant change in polysomnographic parameters, except for a trend toward shorter duration of the longest apnea period (P = 0.0763) following the treatment. Plasmapheresis did not affect polysomnographic parameters despite improved clinical weakness along with decreased myasthenia gravis score and acetylcholine‐receptor antibody concentration.     

Significance of low-level DSA detected by solid-phase assay in association with acute and chronic antibody-mediated rejection

We sought to clarify the controversial issue of whether detecting low‐level anti‐donor‐specific HLA antibody (HLA‐DSA) by single‐antigen flow‐bead assay (SAFB) may have a potential role in reducing acute and chronic antibody‐mediated rejection (AMR). We retrospectively studied the preoperative serum of ABO‐compatible living kidney transplantation recipients transplanted between 2001 and 2004 by SAFB using a Luminex platform. HLA‐DSA was detected only by SAFB in 24 patients, although all of them showed negative T‐cell and B‐cell complement‐dependent cytotoxicity (CDC) crossmatches. The HLA‐DSA patients went on to have surprisingly high levels of acute and chronic AMR despite being only weakly sensitized (acute AMR, 33.3%; chronic AMR, 41.7%). After 2005, we implemented SAFB routinely and any patient having a positive HLA‐DSA was considered to be a desensitization candidate. The 52 patients found to have HLA‐DSA underwent kidney transplantation after prior treatment with a single dose of rituximab (RIT) and three or four sessions of double‐filtration plasmapheresis (DFPP) in addition to regimens commonly used between 2001 and 2004. After 2005, there was a significant reduction in the occurrence of acute and chronic AMR (acute AMR, 4.7%, P < 0.001; chronic AMR, 4.7%, P < 0.001). The 5‐year graft survival rate also improved after implementing SAFB (83.3–98.1%, P = 0.032). The RIT/DFPP‐induction protocol may improve graft survival even in patients with low‐level DSA.     

Lymphocyte subsets and natural killer cell cytotoxicity after laparoscopically assisted resection of rectosigmoid carcinoma

Background: Laparoscopically assisted resection of colorectal carcinoma is technically feasible and minimally invasive. Postoperative immunosuppression also may be reduced. This study compared the lymphocyte subsets and natural killer (NK) cell cytotoxicity in patients after laparoscopically assisted resection with those after open resection of rectosigmoid carcinoma. Methods: In this study, 40 patients with rectosigmoid carcinoma, but no evidence of metastasis, were randomized to receive either laparoscopically assisted or conventional open resection of the tumor. Blood was collected before the operation, then 24 h, 72 h, and 8 days after the operation for studies of lymphocyte subsets and NK cell cytotoxicity. Results: The lymphocyte subsets and NK cell cytotoxicity of both groups showed typical suppression after surgery. The suppression of T cell activation and NK-like T cells was significantly less after laparoscopically assisted resection than in after open resection, whereas the difference in other lymphocyte subsets and NK cell cytotoxicity was not significant. Conclusion: This study showed that some cellular components of the immune system are less suppressed after laparoscopically assisted than after conventional open resection of rectosigmoid carcinoma. This may have implications for tumor recurrence and long-term patient survival.     

The prognostic value of peripheral blood lymphocyte subsets in patients with bladder carcinoma treated using neoadjuvant M-VEC chemotherapy

OBJECTIVES: To assess the prognostic value of peripheral blood lymphocyte subsets in patients with bladder cancer who were treated with neoadjuvant chemotherapy. PATIENTS, SUBJECTS AND METHODS: Thirty patients with a histological diagnosis of invasive bladder transitional cell carcinoma and 30 age-matched controls with no evidence of cancer and immunological disorders were evaluated. Peripheral blood samples were assessed in both groups using monoclonal antibodies. Patients with bladder cancer who achieved complete or partial responses and those who had progression of the disease after systemic chemotherapy with methotrexate, vinblastine, epirubicin and cisplatin were compared according to the pretreatment values of the peripheral blood lymphocyte subsets. RESULTS: There were no significant differences in B lymphocyte levels between the groups. In patients with bladder cancer, the percentages of T lymphocytes (P<0.01), natural killer (NK) cells (P<0.05) and the CD4+/CD8+ ratio (P<0.05) were significantly lower than in the control group. In patients who responded to the chemotherapy regimen, the pretreatment values of T lymphocytes (P<0.001), the CD4+/CD8+ ratio (P<0.01) and NK cell levels (P<0.01) were significantly higher than in the patients who did not. CONCLUSION: In patients with invasive bladder carcinoma, cell-mediated immunity may have a role in the resistance to this malignancy and in these patients the pretreatment levels of T lymphocyte subsets may be an indicator of the potential response to chemotherapy.     

淋巴细胞亚群对乳腺癌新辅助化疗疗效的预测价值

目的 本研究旨在探讨治疗前淋巴细胞亚群对乳腺癌新辅助化疗(NAC)疗效的预测价值.方法 本研究选取2016年4月至2020年6月在中山大学孙逸仙纪念医院接受NAC的乳腺癌患者109例.采用卡方检验及logistics回归分析不同淋巴细胞亚群比例与病理完全缓解(pCR)的相关性,并通过Kaplan-Meier曲线评估其与...     

Immunophenotypic Profile and Increased Risk of Hospital Admission for Infection in Infants Born to Female Kidney Transplant Recipients

Children born to female kidney recipients are exposed to immunosuppressive drugs during gestation. Little is known about their immune system at birth or in the long term. Twenty‐eight children born to female kidney recipients and 40 full‐term children born to healthy mothers were evaluated. T, B, NK, NKT, γδT cells were assessed by flow cytometry and functional evaluation of T and dendritic cells after in vitro activation was performed at birth and at 8 months of age. At birth, infants born to female kidney recipients showed lower numbers of CD4+ T, NKT and intense reduction of B cells (median cells/mm³, transplant: 153.7 X control: 512.4; p < 0.001). There was also a reduced percentage of activated CD8+ T and of CD4+ regulatory T cells. Activated memory and exhausted memory B cells showed higher percentages among children exposed to immunosuppressors when compared to control group. At 8 months, most immune alterations were no longer observed, but four children still had low numbers of some lymphocyte subsets at this age. Children born to female kidney recipients had 4.351 (95% CI: 1.026–15.225; p = 0.046) higher risk of hospital admission in the first months of life—some, with severe clinical manifestations—than those born to healthy women.     

Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome

T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of the study was to determine whether the activity of T-helper-1 (Th1) and T-helper-2 (Th2) cells and the distribution of the lymphocyte subsets, namely CD45RA+CD4+ (”naive” helper T cells, suppressor-inducer), CD45RA+CD8+ (”naive” suppressor T cells, suppressor-effector), CD45RO+CD4+ (”memory” helper T cells), are predictive for steroid sensitivity in children with primary NS. These parameters were assessed at the onset of disease, before initiation of steroid therapy. Two groups of NS children were retrospectively formed according to steroid sensitivity (SS) or resistance (SR). The activity of Th1 and Th2 cells was defined by the production of interleukin-2 (IL-2), interferon-γ, IL-4, and IL-10 in the supernatants of CD4+ T cell cultures activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were determined using double- or triple-color flow cytometry. In SS children with NS we found a decreased proliferative response of CD4+ T cells to TT stimulation, cytokine synthesis indicating the predominance of Th2 activity, and an increased percentage of activated suppressor-inducer (CD45RA+ CD4+CD25+, 5.18±0.8, P<0.001) and suppressor-effector (CD45RA+CD8+CD25+, 2.05±0.6, P<0.01) cells, with the concomitant reduction of activated memory cells (CD45RO+CD4+CD25+, 0.2±0.1, P<0.001). In children with SRNS we found an increased proliferative response of CD4+ T cells to TT, a rise in activated memory (CD45RO+CD4+CD25+, 3.82±0.7, P<0.01) and suppressor-inducer peripheral T cells (CD45RA+ CD4+CD25+, 3.85±0.6, P<0.01), but a low percentage of activated suppressor-effector (CD45RA+CD8+ CD25+, 0.5±0.2, P<0.05) T cells. We conclude that prior to treatment the distribution of lymphocyte subpopulations in peripheral blood together with Th1 and Th2 cell activity provides a useful tool for evaluating the likelihood of steroid sensitivity in patients with primary NS. Received: 3 November 1998 / Revised: 1 September 1999 / Accepted: 8 September 1999     

A prospective observational study of immune reconstitution following transplantation with post‐transplant reduced‐dose cyclophosphamide from HLA‐haploidentical donors

Allogeneic hematopoietic cell transplantation (HCT) from HLA‐haploidentical donors with post‐transplantation high‐dose cyclophosphamide (PT/Cy‐haplo) now predominates worldwide. However, to our knowledge, no prospective study has compared immune reconstitution after PT/Cy‐haplo with that after conventional HCT. The mechanism by which chronic graft‐versus‐host disease (GVHD) is inhibited by PT/Cy‐haplo also remains unknown. We prospectively compared immune recovery patterns of lymphocyte subsets among four groups of adult patients with hematological disease who received HCT from either HLA‐matched related or HLA‐matched unrelated donors, cord blood transplantation, or reduced‐dose PT/Cy‐haplo. Counts of CD4+ T‐cell subsets, CD8+ T‐cell subsets, and NK cells on days 30 and 60 were often lower in PT/Cy‐haplo than those in HLA‐matched related HCT. The immune recovery pace in PT/Cy‐haplo subsequently caught up with that of the other grafts. The regulatory T cells (Tregs) to conventional CD4+ T‐cell (Tcon) ratio was significantly higher until day 90 in PT/Cy‐haplo. In multivariate analysis, a higher Tregs‐to‐Tcon ratio on day 60 was significantly associated with a lower incidence of chronic GVHD (P < 0.01). The preservation of Tregs by PT/Cy in the early phase might have resulted in a lower incidence of chronic GVHD.     

Less Impaired Cell-Mediated Immune Response in the Murine Peritoneal Cavity After CO<Subscript>2</Subscript> Pneumoperitoneum

Purpose. We compared changes in the populations of peritoneal T lymphocytes and natural killer (NK) cells after CO₂ pneumoperitoneum and laparotomy to clarify whether pneumoperitoneum affects cell-mediated immune responses in the peritoneal cavity. Methods. We analyzed and compared populations of T lymphocytes and NK cells among peritoneal exudative cells (PECs) collected from 185 female mice subjected to pneumoperitoneum, laparotomy, or anesthesia only. PECs were collected postoperatively, and the populations of T lymphocytes and NK cell subsets were analyzed by flow cytometry. The NK cell cytotoxicity (NKCC) of PECs and splenocytes was measured. Results. The populations of CD3⁺, CD4⁺, and CD8⁺ lymphocytes in the PECs continued to increase up until postoperative day (POD) 7 after laparotomy. The CD4/8 ratio on POD 3 was significantly lower after laparotomy than after pneumoperitoneum. The percentages of NK cells in the pneumoperitoneum group were significantly lower than those in the laparotomy group. On POD 1, the NKCC of splenocytes was less impaired in the pneumoperitoneum group than in the laparotomy group (10.3% vs 5.0%, P 0.05). Conclusion. Laparoscopic surgery is preferable to open surgery because it results in less impairment of systemic and intraperitoneal cell-mediated immune responses.     

Expression and Prognostic Value of MG7-Ag in Patients With Surgically Resectable Esophageal Squamous Cell Carcinoma

Purpose MG7-Ag is a human gastric-carcinoma-associated antigen. The expression of MG7-Ag was found to increase gradually with the development and progression of gastric cancer. Moreover, a poorer prognosis was found in MG7-Ag positive gastric-carcinoma patients than in MG7-Ag negative patients. However, neither MG7-Ag expression nor its clinical significance has been previously examined in squamous cell carcinoma (SCC) of the esophagus. In this study, we examined the expression of MG7-Ag in esophageal squamous cell carcinomas to assess its value as a prognostic indicator. Methods The expression of MG7-Ag was detected in 112 cases of esophageal squamous cell carcinoma (SCC) by immunohistochemical analysis. The relation of MG7-Ag staining with various clinicopathological features was statistically analyzed. Results The staining of MG7-Ag was detected in SCC, while not in normal epithelial cells. In esophageal SCC, MG7-Ag was found significantly correlated with depth of invasion (P = .012), in T4, T3 carcinomas but not in T2, T1 carcinomas, lymph node metastases (P = .029), pathological stage (P = .005). Consistently, the survival rate tended to be statistically lower in patients with MG7-Ag positive SCCs than in MG7-Ag negative SCCs (P = .005). However, no significant difference was observed between MG7-expression and patient age, sex, tumor location, differentiation, distant metastasis, and lymphatic invasion. Conclusion MG7-Ag might play a positive role in the process of carcinogenesis and progression of esophageal SCC, and it could be considered as one valuable prognostic indicator in esophageal SCC.     

Compartment‐specific expression of natural killer cell markers in renal transplantation: immune profile in acute rejection

Natural killer (NK) cells have been implicated in graft dysfunction. Here, we formulated hypothesis that distinct patterns of expression NK cells markers correlated with acute rejection in kidney transplantation. Therefore, we studied the pattern of NK cell markers CD56, CD57, and CD16 in different compartments of biopsies obtained from recipients diagnosed with acute graft rejection, with or without donor‐specific antibodies (DSA). DSA‐negative biopsies‐from patients with acute T‐cell mediated rejection (aTCMR) had an increased expression of CD56+ and CD57+ cells (P = 0.004 and P = 0.001) in the interstitial compartment in comparison with DSA‐positive biopsies from patients acute antibody‐mediated rejection (aABMR) with (aABMR C4d+) and without C4d deposition (aABMR C4d‐). CD16+ cells was increased (P = 0.03) in the glomerular compartment in DSA‐positive biopsies. We assume that CD16+ expression and antibody‐dependent cellular cytotoxicity (ADCC) in microvascular injury can be associated with aABMR. IFN‐γ release from cytoplasmic granules of NK cell could be associated with aTCMR. Our findings suggest that NK cells need to be carefully evaluated because variations in NK cell marker expression might imply the involvement of different immune system pathways in graft rejection.     

The number of circulating recent thymic emigrants is severely reduced 1 year after a single dose of alemtuzumab in renal transplant recipients

To better understand the kinetics of the delayed reconstitution of peripheral CD4+ T‐cells after depletion with a single administration of alemtuzumab (AL) for renal transplantation, we evaluated in these patients the percentage and absolute number of recent thymic emigrants (RTEs) CD4+ T cells, together with naive and memory subsets, defined by the analysis of CD31, CD45RA and CCR7 expression, and compared with patients treated with a nondepleting protocol based on basiliximab, and with healthy controls. In AL‐treated patients, the number of circulating CD4+ T cells was greatly reduced 1 year after the infusion (P < 0.01), but the proportions of central memory, effector memory and terminally differentiated effector memory subsets among CD4+ cells were significantly increased. On the contrary, the proportion and the absolute number of naïve CD4+ T cells, although progressively increasing with time, were severely reduced. In particular, the absolute number of RTEs had only very slight increase with time (P = 0.049) and was dramatically low 1 year after the therapy (P < 0.01 vs. healthy controls; P < 0.05 vs. basiliximab‐treated transplant recipients). These data suggest that a prolonged defective thymic output after AL therapy in renal transplant recipients is one of the main causes of the persistent CD4+ T‐cell lymphopenia observed in these patients.     

不同全麻对口腔恶性肿瘤患者免疫功能的影响

目的 评价不同全麻对口腔恶性肿瘤患者免疫功能的影响.方法 择期拟行口腔恶性肿瘤根治术患者60例,年龄49～64岁,体重50～71kg,ASA分级Ⅰ或Ⅱ级,采用随机数字表法,将患者随机分为3组(n=20):Ⅰ组采用全凭静脉麻醉,静脉注射眯达唑仑、瑞芬太尼、顺阿曲库铵和异丙酚麻醉诱导,静脉输注异丙酚和瑞芬太尼维持麻醉;Ⅱ组采用静吸复合麻醉,麻醉诱导同Ⅰ组,吸入七氟醚或静脉输注异丙酚复合瑞芬太尼维持麻醉;Ⅲ组采用吸入全麻,吸入七氟醚,静脉注射瑞芬太尼和顺阿曲库铵麻醉诱导,吸入七氟醚,静脉输注瑞芬太尼维持麻醉.于麻醉诱导前30 min(T0)、麻醉后1、3、5 h、术毕、术后24、48、72 h(T2～7)时采集外周静脉血,采用流式细胞仪测定T淋巴细胞亚群及NK细胞、B淋巴细胞百分比.结果 与T0时比较,Ⅰ组～Ⅲ组T1-5时CD3+、CD4+、CD4+/CD8+比值、NK细胞百分比和B淋巴细胞百分比降低,Ⅱ组和Ⅲ组T6时CD3+、CD4+、CD4+/CD8+比值及NK细胞百分比降低(P＜0.05或0.01);与Ⅰ组比较,Ⅱ组T2,3,6时CD4+、CD4+/CD8+比值和Ⅲ组T2～6时CD3+、CD4+、CD4+/CD8+比值及NK细胞百分比降低(P＜0.05或0.01);与Ⅱ组比较,Ⅲ组T4.5时CD4+、CD4+/CD8+比值及NK细胞百分比降低(P＜0.05).结论 与吸人麻醉和静吸复合麻醉比较,咪达唑仑、瑞芬太尼和异丙酚全凭静脉麻醉对口腔恶性肿瘤患者免疫功能的抑制程度较低.

Abstract：

Objective To investigate the effects of different general anesthesia protocols on immune function in patients with oral malignant tumor. Methods Sixty ASA Ⅰ or Ⅱ patients undergoing elective radical operation for oral malignant tumor were randomly divided into 3 groups ( n = 20 each): group Ⅰ total intravenous anesthesia (TIVA); group Ⅱ combined intravenous-inhalational anesthesia (IV-INH) and group Ⅱ inhalational anesthesia (INN). Anesthesia was induced and maintained with propofol and remifentanll in group Ⅰ; with sevoflurane,propofol and remifentanil in group Ⅱ and with sevoflurane and remifentanil in group Ⅲ. Peripheral venous blood samples were taken at 30 min before (To) and 1 h (T1), 3 h (T2 ) and 5 h (T3) after induction of anesthesia, the end of operation (T4 ) and at 24 h (T5 ), 48 h (T6 ) and 72 h (T7) after operation for determination of the percentages of T lymphocyte subsets (CD3+ , CD4+ , CD8+ , CD4+/CD8+ ratio). Natural killer (NK) cells (CD16+ ,CD56+ ) and B lymphocyte (CD19+ ) with flow cytometer. Results The percentages of CD3+ , CD4+ , NK cells, B lymphocyte and CD4+/CD8+ ratio were significantly decreased during and after operation at T1-5 in all groups and the percentges of CD3+ ,CD4+ ,NK cells and CD4+/CD3+ ratio were decreased at T6 in groups Ⅱ and Ⅲ as compared with the baseline values before anesthesia at To. The percentage of CD4+ cells and CD4+/CD8+ratio were significantly lower during anesthesia at T2,3,6 in group Ⅱ than in group Ⅰ . The percentages of CD4 +and NK cells and CD4+/CD8+ ratio were significantly higher after operation at T4,5 in group Ⅱ than in group Ⅲ.The percentages of CD3 + , CD4 + , NK cells and CD4 +/CD8 + ratio were significantly lower at T2-6 in group Ⅲthan in group Ⅰ . Conclusion TIVA with midazolam, propofol and remifentanil has less impact on immune function than inhalational and combined intravenous-inhalational anesthesia in patients with oral malignant tumor under-going elective radical operation.     

肾移植术后稳定状态受者淋巴细胞亚群的动态变化及其与肾功能的相关性分析

目的  探讨肾移植术后稳定状态受者外周血淋巴细胞亚群的动态变化及其与肾功能的相关性。方法  筛选行首次肾移植且术后半年内移植肾功能稳定的受者45例, 采用流式细胞术(FCM)检测受者术后15 d及1、3、6个月共计180份外周血样本淋巴细胞亚群比例和绝对值。分析淋巴细胞亚群随术后时间延长的动态变化及其与血清肌酐(Scr)和血尿素氮(BUN)的相关性。结果  受者术后4个时间点Scr值比较, 差异均无统计学意义(均为P > 0.05)。术后15 d与术后1个月、术后1个月与术后3个月BUN比较, 差异均有统计学意义(P=0.002、P=0.001);术后15 d与术后1个月比较, CD3⁺CD8⁺T细胞、CD3⁺CD4⁺T细胞、自然杀伤(NK)细胞比例及CD4/CD8比值, 差异均有统计学意义(P=0.009、P=0.004、P < 0.001、P=0.004)。B细胞比例术后15 d与术后1个月比较、术后1个月与术后3个月比较, 差异均有统计学意义(均为P < 0.001)。CD3⁺T细胞、CD3⁺CD8⁺T细胞、CD3⁺CD4⁺T细胞和NK细胞绝对值术后15 d与术后1个月比较, 差异均有统计学意义(P=0.001、P=0.002、P=0.003、P < 0.001)。CD3⁺CD8⁺T细胞绝对值术后3个月和术后6个月比较, 差异有统计学意义(P=0.015)。B细胞绝对值术后1个月与术后3个月比较, 差异有统计学意义(P=0.001)。淋巴细胞亚群比例和绝对值与Scr均不相关(均为P > 0.05), CD3⁺CD8⁺T细胞、NK细胞比例和绝对值与BUN均呈负相关(P < 0.001~0.05), CD3⁺CD4⁺T细胞、B细胞比例与BUN均呈正相关(P < 0.001~0.05), CD3⁺T细胞绝对值与BUN呈负相关(P < 0.05)。结论  肾移植术后稳定状态受者的淋巴细胞亚群中T细胞和NK细胞术后1个月内升高至稳定状态, B细胞术后3个月内降低至稳定状态, 且淋巴细胞亚群的动态变化与BUN相关。     

冷冻消融治疗软组织肉瘤后外周血T细胞亚群变化与患者生存期的相关性

目的 观察冷冻消融治疗软组织肉瘤(STS)后外周血T细胞亚群变化及其与患者生存期的相关性。方法 纳入22例接受冷冻消融治疗的晚期STS患者,比较治疗前、后外周血T细胞亚群变化,分析影响患者生存期的相关因素,以及总生存期(OS)和无进展生存期(PFS)与外周血T细胞亚群变化的相关性。结果 共对22个病灶实施冷冻消融。治疗后疾病客观缓解率为81.82%(18/22),患者中位OS为15个月,中位PFS为7个月。OS与肿瘤病理分级和消融效果相关(P均<0.01)。治疗后外周血CD4⁺T、Treg细胞较治疗前降低、自然杀伤(NK)细胞较前升高(P均<0.05);患者PFS与NK细胞水平呈正相关(r=0.539,P=0.010),OS与Treg细胞水平呈负相关(r=-0.463,P=0.030),PFS则与治疗前、后外周血CD4⁺T细胞差值呈正相关(r_s=0.424,P=0.049)。结论 冷冻消融治疗STS可在一定程度上改善机体免疫功能;治疗后血清NK、Treg细胞水平可用于评估患者生存期。     

Double-Filtration Plasmapheresis Plus Low-Dose Anti-thymocyte Globulin and Tacrolimus in Asian Living-Donor Kidney Transplantation With Donor-Specific Anti-HLA Antibody

BackgroundPretransplant desensitization protocols, including plasmapheresis, intravenous immunoglobulin, induction antibody therapy, and intensive maintenance immunosuppression, are generally employed in kidney transplant recipients who have positive status for donor-specific anti-HLA antibody (DSA). To avoid serious infectious complications, the authors designed a novel low-dose protocol in Thai patients undergoing DSA+ living-related kidney transplantation (LRKT).MethodsA retrospective cohort study of the patients who underwent DSA+ LRKT was conducted. The novel protocol consisted of 3 to 5 sessions of pretransplant double-filtration plasmapheresis (DFPP) with or without low-dose intravenous immunoglobulin together with low-dose anti-thymocyte globulin (ATG) induction (1-1.5 mg/kg/d for 3-4 days) and low-dose tacrolimus (Tac) (trough level 5-10 ng/mL), mycophenolate, and prednisolone.ResultsThe study included 17 patients. The lymphocyte crossmatch via complement-dependent cytotoxicity was negative in 12 patients and positive for B cell immunoglobulin M in 5 patients. The novel desensitization protocol resulted in a decrease of at least 50% of DSA mean fluorescence intensity from baseline (from 4320 ± 549 before DFPP to 1601 ± 350 before transplantation, P < .005) and successful kidney transplantation with good allograft function in all cases. Early DSA rebound was observed in 3 patients after transplantation, and kidney biopsy revealed subclinical antibody-mediated rejection in 1 patient and diffuse C4d staining without cell infiltration in 2 patients. There were good long-term outcomes in patient and graft survival (100% and 94.1%, respectively). Only 1 allograft loss occurred because of nonadherence. The majority of patients have stable allograft function with serum creatinine less than 1.5 mg/dL. However, infections, including CMV and other organisms, were commonly observed.ConclusionsDesensitization protocol with DFPP, low-dose ATG, and Tac provides excellent outcomes in living donor kidney transplantation in highly sensitized Asian populations.     

静脉铁剂影响肾性贫血小鼠组织中T淋巴细胞亚群分布的实验研究

目的：观察并比较低分子右旋糖酐铁、蔗糖铁两种常用的静脉铁剂对肾性贫血小鼠不同组织中T淋巴细胞亚群分布的影响。方法：构建肾性贫血小鼠模型,尾静脉注射静脉铁剂24h后,分离小鼠外周血、肝脏、脾脏、肾脏中单个核细胞,利用流式细胞仪分析辅助性T（Thelp、T）细胞、抑制性T（Ts、Ts）细胞、自然杀伤（natural killer,NK）细胞在不同组织中的分布。结果：接受静脉铁剂后,小鼠肝脏和肾脏中Th细胞的比例下调,差异有统计学意义（P〈0.05）,同时铁剂在脾脏、肝脏和肾脏中还不同程度地提高T细胞向Ts细胞分化的比例,同样差异有统计学意义（P〈0.05）。另外,静脉铁剂还抑制了外周血、肝脏和脾脏中NK细胞的分布,差异有统计学意义（P〈0.05）。结论：静脉铁剂可以单独也可协同尿毒症一起导致机体多脏器中免疫微环境的紊乱。     

外周血淋巴细胞亚群绝对值和功能的动态监测在肾移植术后早期病毒感染风险预测中的价值

目的  探讨不同淋巴细胞亚群的绝对值和功能对于评估肾移植受者术后早期发生病毒感染风险的预测和诊断价值。方法  将95例肾移植受者纳入前瞻性观察队列研究,根据术后的免疫状态分为稳定组（77例）和感染组（18例）。分别于术前、术后2周、术后1个月、术后2个月、术后6个月采集外周血样本进行流式细胞检测。比较两组CD4⁺T细胞、CD8⁺T细胞、自然杀伤（NK）细胞绝对值的动态变化,通过检测干扰素（IFN）-γ⁺CD4⁺T细胞、IFN-γ⁺CD8⁺T细胞、IFN-γ⁺NK细胞比例分析两组受者淋巴细胞亚群功能,评估淋巴细胞亚群绝对值和功能在肾移植术后早期对病毒感染的预测和诊断价值。结果  在病毒感染时,感染组的CD4⁺T细胞、CD8⁺T细胞、NK细胞绝对值整体处于相对较低的水平;在术后2个月时,感染组的CD4⁺T细胞、NK细胞绝对值均低于稳定组;在术后6个月时,感染组的CD4⁺T细胞、CD8⁺T细胞绝对值均低于稳定组（均为P < 0.05）。在病毒感染时,感染组的IFN-γ⁺CD4⁺T细胞、IFN-γ⁺CD8⁺T细胞、IFN-γ⁺NK细胞比例均处于相对较低的水平,尤以IFN-γ⁺CD8⁺T细胞比例降低最为显著;在术后2个月,感染组的IFN-γ⁺CD8⁺T细胞、IFN-γ⁺NK细胞比例显著高于稳定组;在术后6个月,感染组的IFN-γ⁺CD4⁺T细胞、IFN-γ⁺CD8⁺T细胞比例均高于稳定组（均为P < 0.05）。logistic回归分析结果显示,术后2个月时,IFN-γ⁺CD8⁺T细胞和IFN-γ⁺NK细胞比例的升高与病毒感染风险增加均相关（均为P < 0.05）。受试者工作特征（ROC）曲线结果表明,淋巴细胞亚群绝对值联合其IFN-γ分泌功能对于免疫状态低下的受者病毒感染的诊断价值显著高于单用淋巴细胞亚群绝对值（P < 0.05）。结论  动态监测淋巴细胞亚群绝对值和功能的变化对病毒感染的预测、诊断及指导用药具有重要参考价值。     

CIMETIDINE PRESERVES NON-SPECIFIC IMMUNE FUNCTION AFTER COLONIC RESECTION FOR CANCER

Fifty consecutive patients undergoing resection of colorectal cancer were randomized to either receive cimetidine at a dose of 400 mg bd for a minimum of 5 pre-operative days, then intravenously for 2 postoperative days, or to act as controls. Baseline immune function was determined in all patients by in vitro testing of lymphocyte proliferation (LP) in response to mitogen, skin testing for cell mediated immunity (CMI) and measurement of lymphocyte subsets. Immune function was retested in both groups on the second postoperative day. In control patients the mean postoperative LP value was 41% of pre-operative levels (P < 0.0001) and the mean CMI reduced to 29% (P < 0.0001). Patients treated with cimetidine had no significant fall in these parameters. Numbers of T and natural killer (NK) cells fell after surgery in both groups, and B cell numbers were maintained in the cimetidine group. It is concluded that cimetidine reduces the immunosuppression that follows colonic resection.