Increased HLA-A*11 in Chinese children with steroid-responsive nephrotic syndrome

Human leukocyte antigen (HLA) associations have been frequently reported in childhood steroid-responsive nephrotic syndrome (SRNS) in other populations. The aim of this study was to characterize the immunogenetic background of Singaporean Chinese patients with childhood SRNS. We determined the HLA class I (HLA-A* and HLA-B*) as well as class II (HLA-DRB1*, HLA-DQB1*) gene polymorphisms using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique, in patients with SRNS (n=64) and normal controls (n=236 for HLA-A*, n=80 for HLA-B*, HLA-DRB1* and HLA-DQB1*). The frequency of HLA-A*11 allele was significantly higher in the SRNS patients compared to controls (78.1% vs 54.2%, respectively; relative risk, RR=3.01, Pc=0.011). However, there was no significant difference in the allele frequencies of HLA-B*, HLA-DRB1* and HLA-DQB1* between the SRNS patients and controls, unlike that in previous studies. Our data suggest that the immunogenetic background of Singaporean Chinese with childhood SRNS was different from that in other populations. As HLA-A*11 has been strongly associated with other autoimmune diseases, it is conceivable that the HLA-A*11-specific motif may play a role in the development of the abnormal T-cell-mediated immune response that may be responsible for triggering the proteinuria seen in SRNS. Received: 24 April 2001 / Revised: 14 November 2001 / Accepted: 18 November 2001     

肾移植受者抗HLA抗体监测的临床意义

目的探讨动态监测肾移植受者抗HLA抗体的临床意义。方法采用酶联免疫吸附试验(ELISA)对1517例肾移植受者进行手术前、后血清群体反应性抗体(panel reactive antibody,PRA)强度动态监测,对PRA阳性受体进一步行抗HLA抗体分型并进行随访,观察PRA水平对移植物长期存活和移植肾功能的影响。结果1517例中,术前PRA阴性者1336例,阳性者181例。术前PRA阳性受者和阴性受者的移植物功能延迟恢复(DGF)发生率分别为34.8%、11.9%,两组比较差异有统计学意义(P0.01)。术前PRA阳性受者的移植肾1、3、5、8年存活率分别为94%、85%、73%和63%,术前PRA阴性受者相应为96%、87%、72%和65%,两组比较差异均无统计学意义(P0.05)。移植前及移植6个月后PRA均为阴性的265例受者中,血清肌酐水平异常者仅占19.6%,而术后PRA转为阳性的57例受者中,血清肌酐异常者高达61%,两者比较差异有统计学意义(P0.01);移植前PRA阳性的53例受者中,有24例移植后PRA转为阴性,术后血清肌酐全部正常。结论术前筛查PRA可科学评估肾移植患者的体液致敏状态,为致敏患者选配合适供者;术后监测PRA可及时了解移植肾的免疫状态,有利于防治排斥反应。     

人类白细胞抗原-DRB1基因多态性与山西省家族性乙型肝炎预后的相关性研究

目的探讨人类白细胞抗原（human lymphoeyte antigen,HLA）-DRB1等位基因多态性与山西省家族性乙型肝炎临床转归及乙型肝炎病毒（HBV）复制状态的相关性。方法采用前瞻性临床流行病学研究方法,以山西省家族性乙型肝炎家庭中的295位成员为研究对象,将其分为健康对照组、慢性无症状携带（ASC）组、慢性乙型肝炎（CHB）组及肝硬化组。采用聚合酶链反应．序列特异性寡核苷酸探针技术（polymerase chain reaction—sequence specific oligonucleotide probe,PCR—SSOP）结合荧光磁珠流式检测技术,进行HLA—DRB1等位基因检测。采用,检验或Fisher’s确切概率计算法比较HLA—DRB1各等位基因频率在各组间以及在HBV DNA不同载量下的分布情况,组间计量资料比较采用方差分析,相关疾病的等位基因风险率以相对危险系数（RR）表示。结果HLA—DRB＊04基因频率在健康对照组为0．159,明显高于ASC组（0．069）和CHB组（0．079）,差异具有统计学意义（χ^2分别为4．892和4．072,P值均〈0．05）;HLA—DRB1＊07等位基因在CHB组和肝硬化组的频率分别为0．131和0．154,明显高于健康对照组（0．049）,差异具有统计学意义（χ^2值分别为4．140和5．529,P值均〈0．05）;HLA—DRB1＊13等位基因频率在健康对照组为0．037,高于CHB组（0）,2组比较差异具有统计学意义（χ^2=3．316,P〈0．05）。HLA—DRB1＊15等位基因频率在ASC组为0．206,在肝硬化组为0．115,2组比较差异具有统计学意义（χ^2=4．287,P〈0．05）。其他各等位基因频率在各组间差异无统计学意义。患者年龄在ASC、CHB及肝硬化3组间的差异有统计学意义（F=33．38,P〈0．01）;HBV DNA阳性组的HLA—DRB1＊07基因频率（0．167）高于HBV DNA阴性组（0．096）（χ^2=5．268,P=0．002）。结论HLA—DRB1＊07与家族性HBV易感性有关,可能是山西省家族性乙型肝炎易感基因或连锁基因。HLA—DRBI＊04及HLA—DRB1＊13与家族性乙型肝炎抗性相关,可能是山西省家族性乙型肝炎抗性基因。     

Kidney Transplantation in Patients with Antibodies against Donor HLA Class II

The immunologic risk associated with donor-specific antibodies (DSA) against Class II human leukocyte antigens (HLA) in kidney transplant (KTx) recipients is unclear. The aim of this study was to determine the outcome of KTx when DSA was detected only against HLA Class II. To isolate the impact of anti-Class II DSA, we retrospectively analyzed 12 KTx recipients who at baseline had a positive B-cell flow cytometric crossmatch (FXM) and a negative T-cell FXM. Using alloantibody specification analysis, 58.3% (7/12) had DSA against donor Class II and 41.7% had no demonstrable DSA. Biopsy-proven AMR occurred in 57% (4/7) in the Class II(+) group and 0% in the Class II(-) group (p > 0.05). Peritubular capillaries stained positive for C4d in 86% (6/7) of the Class II(+) patients and in 40% (2/5) of the Class II(-) patients (p > 0.05). One patient in the Class II(+) group lost their graft at 3 months to accelerated transplant glomerulopathy, while all other grafts were functioning 3-37 months posttransplant despite the persistence of anti-Class II DSA. We conclude that KTx recipients with clearly defined anti-Class II DSA are at risk for humoral rejection suggesting that desensitization and/or close posttransplant monitoring may be needed to prevent AMR.     

四配子异源嵌合体导致的真两性畸形机制研究

目的 :报告 1例四配子异源嵌合体导致的真两性畸形并讨论其发病机制。　方法 :对 1例外生殖器模糊的患者外周血的淋巴细胞、经培养的皮肤成纤维细胞、两种不同性腺组织的成纤维细胞进行染色体核型分析 ,同时用X和Y染色体探针进行双色荧光原位杂交 (FISH) ;对患者红细胞血型、人类白细胞抗原 (HLA)和 77个短重复序列 (STR)微卫星标记进行检测 ;对患者性腺的 2种不同组织进行组织病理学检查 ;同时对患者的父母进行红细胞血型、HLA和STR检测。　结果 :患者外周血淋巴细胞、皮肤成纤维细胞、呈白色和黄色性腺组织的成纤维细胞染色体核型均为 4 6 ,XX/ 4 6 ,XY ;FISH检测所有细胞都显示了XX或XY的杂交信号。 4 6 ,XY的核型在外周血淋巴细胞、皮肤成纤维细胞和白色性腺组织的成纤维细胞中占优势 ;4 6 ,XX的核型在黄色性腺组织的成纤维细胞中占优势。外周血淋巴细胞及 3种不同组织培养物的STR位点检测、ABO血型分析和HLA检测都显示有 2个不同的单倍体来自父亲 ,1个单倍体来自母亲。组织病理学检查患者同一性腺上有两种不同组织 ,呈白色的组织是睾丸 ,呈黄色的组织是卵巢。　结论 :性腺组织病理学检查、染色体核型分析、FISH是鉴定真两性畸形患者的有效方法 ,红细胞血型、HLA和STR可为鉴定四配子异源嵌合体提供?     

Identification of HLA‐DR4‐restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule

Park C‐S, Kim K‐H, Im S‐A, Song S, Lee C‐K. Identification of HLA‐DR4‐restricted immunogenic peptide derived from xenogenic porcine major histocompatibility complex class I molecule. Xenotransplantation 2012; 19: 317–322. © 2012 John Wiley & Sons A/S. Abstract: Indirect recognition of xenoantigens has been implicated as the major mechanism underlying xenospecific CD4⁺ T‐cell activation in chronic rejection. We identified swine leukocyte antigen (SLA)‐derived immunogenic peptides that are presented in the context of human HLA‐DR4 molecules. The SLA class I‐derived peptides that bind HLA‐DRB1*0401, a representative of the DR4 supertype, were predicted using a computer‐assisted algorithm. The candidate peptides were synthesized, and their binding capacities to HLA‐DRB1*0401 were compared in a competitive ELISA using biotinylated hemagglutinin reporter peptides [HA_307‐319]. Peptide‐11 (LRSWTAADTAAQISK) was determined to exhibit the most potent binding capacity to HLA‐DRB1*0401 in vitro and thus selected for in vivo immunization. Immunization of HLA‐DRB1*0401‐transgenic mice with peptide‐11 elicited potent CD4⁺ Th1 responses. Peptide‐11 shares homology to α2 domains of three SLA‐1 alleles, six SLA‐2 alleles, and 14 SLA‐3 alleles. Thus, this study has important implications not only for the identification of an immunogenic indirect epitope shared by diverse SLA class I alleles, but also for the development of epitope‐specific immunoregulation strategies.     

The Leukocyte Esterase Strip Test has Practical Value for Diagnosing Periprosthetic Joint Infection After Total Knee Arthroplasty: A Multicenter Study

Background

Leukocyte esterase (LE) was recently reported to be an accurate marker for diagnosing periprosthetic joint infection (PJI) as defined by the Musculoskeletal Infection Society (MSIS) criteria. However, the diagnostic value of the LE test for PJI after total knee arthroplasty (TKA), the reliability of the subjective visual interpretation of the LE test, and the correlation between the LE test results and the current MSIS criteria remain unclear.

The safety,efficacy, and cost-effectiveness of intraoperative cell salvage in metastatic spine tumor surgery

Background Context

Metastatic spine tumor surgery (MSTS) is associated with substantial blood loss, therefore leading to high morbidity and mortality. Although intraoperative cell salvage with leukocyte depletion filter (IOCS-LDF) has been studied as an effective means of reducing blood loss in other surgical settings, including the spine, no study has yet analyzed the efficacy of reinfusion of salvaged blood in reducing the need for allogenic blood transfusion in patients who have had surgery for MSTS.

The association between killer‐cell immunoglobulin‐like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

BK virus is a common opportunistic post‐transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two‐year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin‐like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post‐transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.