强直性脊柱炎患者HLA-B27和免疫指标检测的临床意义

目的:探讨HLA-B27和免疫指标在强直性脊柱炎(AS)患者的临床意义.方法:采用流式细胞术检测147例AS患者、95例正常对照者的HLA-B27、CD3 T、CD4 T、CD8 T、CD19 B,用免疫比浊法检测IgA、IgG和IgM.结果:AS患者HLA-B27、CD3 T、CD4 T淋巴细胞的百分率及CD4 /CD8 的比值、血清IgA、IgG均明显高于正常对照组(P＜0.01);CD8 T淋巴细胞的百分率低于正常对照组(P＜0.05);CD19 B淋巴细胞的百分率高于正常对照组(P＜0.05);IgM与正常对照组相比无显著性差异.结论:HLA-B27、CD3 T、CD4 T与AS密切相关,提示,HLA-B27与CD3 T、CD4 T、CD4 /CD8 的比值可作为AS辅助诊断指标.     

遂宁地区疑似强直性脊柱炎患者HLA-B27抗原阳性率分析

目的通过观察遂宁地区疑似强直性脊柱炎患者的HLA-B27抗原阳性分布情况,分析其阳性率和抗原表达强度在不同性别疑似病例中存在的差异。方法收集遂宁地区1598例疑似强制性脊柱炎患者HLA-B27抗原检测报告,分析其阳性率在不同性别疑似病例中是否存在差异,并根据流式细胞术检测到的外周血T淋巴细胞膜上HLA-B27抗原荧光强度,分析不同性别的阳性疑似病例抗原表达强度是否存在差异。结果 1598例疑似病例中HLA-B27抗原阳性病例有394例,阳性率为24.7%。男性疑似病例HLA-B27抗原阳性率(31.7%)高于女性疑似病例HLA-B27抗原阳性率(15.6%),差异具有统计学意义(P.0.01);男性HLA-B27抗原阳性者的抗原表达强度为(157.42±11.91),女性HLA-B27抗原阳性者的抗原表达强度为(157.56±13.4),两者之间无统计学差异(P0.05)。结论遂宁地区强直性脊柱炎疑似病例的HLA-B27抗原阳性率较正常人群显著增高,且男性阳性率显著高于女性,HLA-B27抗原检测有助于强直性脊柱炎的早期筛查、诊断和治疗。     

流式细胞术检测HLA-B27及其临床意义

目的通过流式细胞术检测外周血白细胞HLA-B27的表达,并探讨其对强直性脊柱炎(AS)的诊断价值。方法利用流式细胞仪(FCM)检测41例AS患者、62例背痛及腰腿痛患者及112例健康体检者的外周血HLA-B27表达。结果 41例AS患者中,HLA阳性38例(92.6%);62例背痛腰腿痛患者中,HLA-B27阳性6例(9.67%);112例健康人群中,HLA-B27阳性2例(1.78%)。结论 AS患者HLA-B27阳性率明显增高,HLA-B27检测可视为临床支持AS诊断的重要依据。     

B细胞活化因子及其受体BR3在强直性脊柱炎患者外周血白细胞中的表达及临床意义初探

为了探讨强直性脊柱炎(AS)患者外周血白细胞中B细胞活化因子(BAFF)及其受体(BR3)的表达水平及其临床意义.采用流式细胞术检测24例AS患者、30名健康体检者外周血白细胞上BAFF、BR3的表达水平,并比较其与红细胞沉降率(ESR)、C反应蛋白(CRP)、免疫球蛋白(IgG、IgA、IgM)的相关性.结果显示.A...     

维生素A营养状况对人体免疫功能的影响及补充效果观察

自大学生及青年职工中筛选血红蛋白、血清白蛋白及维生素E在正常范围的受检者71名,测定血清维生素A含量及外周血T淋巴细胞百分数、植物血凝素(PHA)诱导的淋巴细胞转化率、免疫球蛋白(IgG、IgA、IgM)、补体C3含量等6项免疫学指标。结果显示,血清维生素A平均含量为38.9±12.4μg/dl,当各项免疫指标的相关分析结果,维生素A与外周血T淋巴细胞百分数和淋巴细胞转化率间呈正相关(r=0.2366 P<0.05,r=0.3086 P<0.01),与IgG、IgA、IgM及补体C3含量未见相关性.维生素A含量     

肝胆胰疾病患者十一种血清蛋白质定量测定及其临床意义

收集114例临床确诊肝胆胰疾病患者血清,应用贝克曼全自动免疫分析仪(Array Protein Systen m)联合定量检测11种血清蛋白质,发现胆管结石及胆囊疾病患者血清IgG、IgA,IgM、AAT和AMG升高,TRF和CER降低,而C3、C4、AAG和CRP正常;胰腺疾病IgG、IgA和AAT升高,TRF和CER降低,IgM、C3、C4、AAG、AMG及CRP正常;肝癌患者IgG、IgA、IgM、AMG、AAT和CRP升高,TRF降低,C3、C4、AAG和CER正常;肝硬化患者IgG、IgA、IgM、AMG和AAT升高,C3、C4、TRF、AAG和CER降低,CRP正常.肝胆结石与非肝胆结石患者比较,血清IgG、IgA、IgM、CER和AMG降低,C3和C4升高,这对临床鉴别诊断有一定意义.肝胆结石患者手术后CRP、IgA和AAG明显升高,是术后观察的有用指标.11种血清蛋白质分别与Bil-T、ALP和ALT测定结果作相关性分析,发现C3与ALP、TRF与ALT呈正相关,其余蛋白质与Bil-T、ALP和ALT则相关不显著(P>0.05).     

炎症相关性指标在评价强直性脊柱炎活动性中的价值

目的探讨强直性脊柱炎(ankylosing spondylitis,AS)患者各炎症相关性指标与疾病活动性的相关性。方法依据Bath强直性脊柱炎活动性指标(BASDAI)将60例AS患者分为36例活动组和24例静止组,比较2组AS患者的各项实验室指标,并与30例健康对照者做对比。结果活动组AS患者ESR、CRP、IgA、IgG明显高于与静止组和正常对照组(P<0.01),而WBC、PLT、IgM、C3、C4无统计学差异(P>0.05);ESR、CRP、IgA与BASDAI存在正相关(P<0.01);IgA与ESR、CRP存在正相关(P<0.01)。结论除了ESR和CRP外,IgA也可作为反映AS疾病活动性的一项实验室指标。     

强直性脊柱炎患者血液HLA-B27的临床参考值的预测

目的 以实时荧光定量PCR（FQ-PCR）检测可疑患者HLA-B27的定量水平,研究强直性脊柱炎（AS）与HLA-B27的相关性,明确HLA-B27的检测值范围并用于AS的确诊诊断.方法 针对本院2005年~2010年收集的168例骶髂关节及下腰部疼痛等症状疑似AS病例进行回顾性分析,获得所有病例外周静脉血标本,然后通过实时荧光定量PCR进行HLA-B27的定量检测,疑似病例分为AS患者、HLA-B27阳性的非AS患者、HLA-B27阴性的非AS患者三组,根据临床体征、影像学进行确诊病情,同时选取健康体检者52例外周静脉血标本的HLA B-27测定结果进行对照,统计分析各变量与AS存在之间的关系.结果 AS患者、HLA-B27阳性的非AS患者、HLA-B27阴性的非AS患者、健康体检者的HLA-B27循环阈值（ct）平均值分别为：26.3 copies/ml、17.5 copies/ml、6.2 copies/ml、4.9 copies/ml,单变量分析表明,HLA-B27与化脓性关节炎明显相关（P＜0.05）.结论 AS患者HLA-B27定量分析循环阈值（ct）的95%参考值范围为（17.3~35.3）copies/ml,HLA-B27定量分析可作为疾病发病的参照影响因素及预测因素.     

强直性脊柱炎患者检测骨代谢指标潜在的临床价值

目的:探讨骨代谢指标和人类白细胞抗原B27(HLA-B27)在检测强直性脊柱炎(AS)患者的临床意义,并分析其诊断价值。方法:研究对象为94 例AS 患者、239 例其他病种对照和80 例健康对照组,并对其结果进行回顾性分析。结果:AS 组β-胶原特殊序列(β-CTX)高于对照组,而骨钙素(OC)、25 羟基维生素D也25-(OH)D页和甲状旁腺素(PTH)低于对照组(P<0.05);AS 组C 反应蛋白(CRP)和β-CTX 呈明显的正相关(P<0.01),25-(OH)D 呈负相关(P<0.05),其他骨代谢指标和CRP 无相关性;AS 组HLA-B27 阳性率明显高于其他组(P<0.05),且HLA-B27 在诊断AS 时具有很高的敏感性和特异性;AS 组25-(OH)D 检测的敏感性高于β-CTX,但特异性低于β-CTX。结论:骨代谢指标对AS 早期筛查,临床诊断有着重要价值,尤其是β-CTX 和25-(OH)D 的诊断价值更为明显。     

不同分娩方式不同性别新生儿脐血的免疫功能检测

背景：影响新生儿免疫功能有多种因素。新生儿阴道分娩娩出时,子宫收缩会使胎儿处于相对缺血、缺氧状态,新生儿免疫状态受分娩方式的影响;剖宫产新生儿免疫力低,易继发感染。 目的：对比分析剖宫产与阴道分娩对不同性别新生儿脐血免疫功能的影响。 方法：选择足月单胎分娩产妇100例,其中阴道分娩组50例,新生儿男性30例,女性20例;剖宫产组50例,新生儿男性30例,女性20例。采用自动生化分析仪透射免疫浊度法检测两组新生儿脐血免疫球蛋白(IgG、IgA、IgM)、补体(C3、C4)及C-反应蛋白水平,流式细胞仪酶标法测定T淋巴细胞抗原(CD4、CD8)水平。 结果与结论：剖宫产组女性婴儿脐血淋巴细胞CD4抗原、CD4与CD8混合抗原水平显著高于阴道分娩组(P < 0.01),CD8抗原水平却显著低于阴道分娩组(P < 0.01);剖宫产组女性婴儿脐血IgA、IgM水平显著高于男性组(P < 0.01),IgG水平却低于男性组(P < 0.05)。剖宫产组女性婴儿脐血IgG、 IgM、C-反应蛋白水平显著低于阴道分娩组(P < 0.01),男性婴儿脐血IgM水平显著低于阴道分娩组(P < 0.01),C-反应蛋白水平显著高于阴道分娩组(P < 0.01)。提示不同分娩方式对不同性别新生儿免疫功能有影响,剖宫产可降低新生儿的免疫功能。     

HLA-B27-restricted T cells from patients with ankylosing spondylitis recognize peptides from B*2705 that are similar to bacteria-derived peptides

Ankylosing spondylitis (AS) is an inflammatory systemic disease affecting the spine, sacroiliacal and peripheral joints. Although the aetiology of AS remains unknown, the strong association with the HLA-B27 allele might reflect directly a detrimental effect of the HLA-B27 molecule itself, resulting from its potential capability to present 'arthritogenic' peptides to CD8+ T cells. Because some forms of SpA are triggered by enterobacterial infection, such arthritogenic peptides might originate from autologous and/or bacterial proteins triggering cross-reactive CD8+ T cell clones. Intriguingly, two peptides from the second extracellular domain of HLA-B*2705 share sequence homologies with several enterobacterial antigens, exhibit the HLA-B27-binding-motif, and are presented by HLA-B*2705 itself. The objective of this study was to examine the clonal T cell reactivity against these peptides in patients with AS. To this end, we screened peripheral blood lymphocytes (PBL) of 26 patients with AS and 24 healthy donors for TNF-alpha-producing cells using ELISPOT assays. PBL and synovial fluid-derived lymphocytes (SFL) of peptide-responsive patients were then stimulated and cultured with the relevant peptide and control peptides in vitro. Antigen-specific T cell lines (TCL) were identified by standard chromium release assays. Clonal analysis was performed subsequently applying TCRB-CDR3 spectratyping. Among eight peptides tested, only the HLA-B27 168-176 peptide LRRYLENGK was recognized by PBL from B27+ AS patients but not from B27+ healthy controls (P=0.001). LRRYLENGK-specific T cell clones used preferentially the TCRBV5S1 and the BV14 segment. These results suggest that an HLA-B27-derived peptide with homology to bacterial peptides may play a role in AS.     

Induction of arthritis and uveitis in Lewis rats by antigenic mimicry of peptides from HLA-B27 and cytokeratin.

Ankylosing spondylitis (AS) is highly associated with HLA-B27. We have previously shown that peripheral blood lymphocytes from AS patients respond to stimulation with a peptide from the sequence of HLA-B27. Here we report on molecular mimicry of peptides from HLA-B27 and cytokeratin, the latter being specifically expressed in synovial membranes and eyes, the main targets of the autoaggressive immune response in AS patients. Immunization of rats with these peptides induced an inflammatory response in joints, spine and eyes, resembling the symptoms in AS. Furthermore, both HLA-B27- and cytokeratin-derived peptides, are effective oral tolerogens: feeding these peptides ameliorated arthritis and uveitis induced with the cytokeratin peptide. Our model might elucidate the role of peptides from the sequence of HLA-B27 as an antigen of the immune response in AS, introducing a new aspect of antigenic mimicry between HLA-B27 and tissue-specific antigens. We propose this as a mechanism directing a systemic autoimmune response to specific target organs by antigenic mimicry of T cell epitopes.     

Collagen-specific cytotoxic T lymphocyte responses in patients with ankylosing spondylitis and reactive arthritis

Both ankylosing spondylitis (AS) and reactive arthritis (ReA) are strongly associated with HLA-B27 although the mechanism for this association is still unknown. Here we examine the hypothesis that B27-restricted, joint antigen-specific cytotoxic T lymphocytes (CTL) may be the driving force of AS and ReA. Type II and type XI procollagens (CII and CXI, respectively), expressed almost exclusively in the articular cartilage of the joints, were chosen as the possible targets of autoimmune CTL. Type I procollagen (CI), expressed in many different tissues, was also included as control. Nineteen nonamer peptides bearing appropriate HLA-B27 binding motifs from human CI, CII and CXI were identified and synthesized. When analyzed for binding affinity to HLA-B27 in assembly assays, four (two from CII, two from CXI) were found capable of binding to HLA-B27 with high affinity. These B27-binding collagen peptides were then used to stimulate peripheral blood lymphocytes from eight B27-positive AS and three ReA patients for identification of possible B27-restricted autoimmune CTL. HLA-B27-restricted CTL specific for one of the CII peptides, P109 were found in one of the ReA patients, but in none of the others.     

The involvement of NK cells in ankylosing spondylitis

A role for NK cells in the regulation of autoimmunity has been demonstrated. Since there is a strong association between Ankylosing Spondylitis (AS) and HLA-B27, which is specifically recognized by the NK-inhibitory receptor KIR3DL1, this study evaluated the potential involvement of NK cells in AS. We studied 19 AS patients and 22 healthy volunteer donors and assessed the percentage, activity and receptor expression of peripheral blood NK cells. We also evaluated candidate-inflammatory mediators in sera. We found that AS patients have significantly higher percentages of NK cells. However, we found no differences between the ability of NK cells derived from AS and healthy controls to recognize target cells expressing HLA-B27. Remarkably, we observed that the NK-inhibitory receptor CEACAM1 (carcino-embryonic antigen-cell adhesion molecule) is highly expressed among AS-derived NK cells. Furthermore, engagement of CEACAM1 inhibited NK activity in these patients. Finally, we demonstrated that CEACAM1 expression is induced by IL-8 and SDF-1 (stromal cell derived factor), both of which are present in high levels in the sera of AS patients. These results may indicate that NK cells and CEACAM1 play a role in AS pathogenesis and implicate chemokines in the mechanism of CEACAM1 expression.     

The distribution of a specific HLA-B27-associated cell surface component on the tissues of patients with ankylosing spondylitis.

In this paper, we report the presence on Epstein-Barr virus-transformed lymphoblastoid cell lines on platelets and on fibroblasts of an HLA-B27-associated cell surface complex (antigenically related to some antigens of Klebsiella K43 and K21) which is identical to or cross-reactive with the determinant present on the peripheral blood lymphocytes (PBL) of B27-positive patients with ankylosing spondylitis (AS). By contrast, no Klebsiella K43 markers could be demonstrated on the spermatozoa of B27+ AS+ individuals even though these cells expressed the HLA-B27 alloantigen. No B27-associated K43 antigen was detected on the erythrocytes of patients or of normal controls. The B27-associated membrane marker is still detectable on lymphoblastoid cell lines after 20 generations and on fibroblasts after about 10 generations. This finding implies that the continued expression of Klebsiella-modified B27 structure is generally determined and does not require the repeated exposure of the cell surface to Klebsiella antigen. These data suggest that certain non-lymphoid as well as lymphoid cells may be involved in the complex sequence of events leading to the clinical manifestation of AS.     

Increased expression of Toll-like receptor 4 in peripheral blood leucocytes and serum levels of some cytokines in patients with ankylosing spondylitis

Toll-like receptor 4 (TLR4) is a member of the Toll-like receptor family, which can bridge innate and adaptive immune responses. Activation of the TLR4 signalling pathway may induce the release of proinflammatory cytokines such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-12, which was considered to play an important role in pathogenesis of immune-mediated diseases. Ankylosing spondylitis (AS) is an immune-mediated disease whose aetiology remains unknown. The aim of the study was to investigate the expression of TLR4 and serum TNF-alpha, IL-12 and soluble tumour necrosis factor-related apoptosis-inducing ligand (sTRAIL) level in AS patients. The results indicated that TLR4 protein and mRNA levels were significantly higher in AS patients than in healthy controls; however, there was no significant difference between human leucocyte antigen (HLA)-B27-positive and -negative AS patients, as well as serum levels of TNF-alpha, IL-12 and sTRAIL. In addition, in HLA-B27-positive AS patients, TLR4 level showed close associations with the cytokines and laboratory parameters of disease activity [erythrocyte sedimentation rate (ESR) and plasma C-reactive protein (CRP)], respectively. Similarly, the strong associations between the cytokines or between IL-12 and ESR or CRP were observed in HLA-B27-positive AS patients. Interestingly, in HLA-B27-positive AS patients, TNF-alpha correlated significantly with ESR, but did not with CRP. In contrast, sTRAIL correlated with CRP, but did not with ESR. Among HLA-B27-negative patients, no close correlation was found. In our study, it was suggested that the abnormal activation of TLR4 signalling and serum TNF-alpha, IL-12 and sTRAIL may play a key role in the development and progression of AS, which may be dependent on the status of HLA-B27 antigen.     

HLA-A*9, a probable secondary susceptibility marker to ankylosing spondylitis in Basque patients

HLA-B27 is strongly associated to ankylosing spondylitis (AS). The objective of our study was to analyze HLA-B27 association, B27 subtype distribution and frequency of other HLA class I and DR antigens in a group of Basque AS patients. HLA class I antigens were typed serologically and HLA-B27 and A9 subtypes were determined by DNA typing in samples from 46 patients with AS, 54 B27-positive spondyloarthropathies, 82 healthy subjects and 20 B27-positive controls. A class I HLA 9.2 kb PvuII restriction fragment length polymorphism (RFLP), previously associated with AS, was analyzed in a representative group of patients and controls. We found that HLA-B*2705 conferred a relative risk of 126 for AS in this group. HLA-A9 (A*2402) allele was significantly increased in AS patients compared with healthy controls and B27-positive control group (Pcorr<0.0001) and also increased in patients affected with peripheral arthritis. No association between class I HLA 9.2 Kb RFLP and AS was found. These results suggest that HLA-A*9 allele itself or another linked gene could act as a secondary and independent susceptibility allele to AS.     

Prevalence of HLA-B*27 subtypes in the Tamil population of India with Ankylosing spondylitis and its correlation with clinical features

IntroductionHLA-B*27 is strongly associated with Ankylosing spondylitis (AS). Its subtypes show considerable geographic and ethnic difference. The main aim of this study was to assess the frequency of subtypes of HLA-B*27 in the Indian Tamil AS patients.Methods and materialsAdult AS patients positive for HLA-B*27 were considered for the study. The high-resolution typing to define HLA-B*27 subtypes were done using Invitrogen B kits from One Lambda (SeCore® Sequencing Kits, Thermo Fisher, United States).Results and conclusionPrevalence of subtypes identified were HLA-B*27:04 (52.2%), HLA-B*27:05 (41.6%), HLA-B*27:07 (3.5%) and HLA-B*27:02 (2.7%). All subtypes showed disease predisposition for males. The most common extra articular manifestation seen was enthesitis in HLA-B*27:04 and HLA-B*27:05. Uveitis was mainly associated with HLA-B*27:05 and dactylitis with HLA-B*27:04. A significant peripheral joints involvement for female and axial joint involvement for males was seen in HLA-B*27:04. Our study establishes the prevalence of HLA-B*27 subtypes and the associated clinical phenotypes among the Indian Tamil population. Considering the variability of presentation, organ involvement, and disease course in different subtypes and across ethnicities it is critical to define these associations in the ethnic populations we treat for their appropriate care considering the significant negative health and socioeconomic effects of AS.