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.     

疑似强直性脊柱炎患者HLA-B27与B13抗原关联的分析

ＨＬＡ Ｂ2 7与强直性脊柱炎 (ＡＳ)发病相关已得到公认。美国、加拿大、挪威和荷兰白种人的ＨＬＡ Ｂ6 0抗原可增加ＨＬＡ Ｂ2 7阳性个体的ＡＳ易感性〔1〕。我们在对疑似ＡＳ患者检测ＨＬＡ Ｂ2 7抗原中 ,发现相当多的患者存在ＨＬＡ Ｂ2 7/Ｂ13抗原关联现象 ,结果如下。材料与方法检测对象 :1999年 1月～ 2 0 0 1年 5月期间 ,由我室进行ＨＬＡ Ｂ2 7检测的来自江苏、安徽两省的 75 0名临床怀疑为ＡＳ的患者 ,男性 5 37人 ,女性 2 13人。检测方法 :采用微量淋巴细胞毒法 (ＮＩＨ标准 )。试剂由ＯｎｅＬａｍｂｄａ公司 (美国 )提供 ,每次实…     

HLA-B27 PCR辅助诊断幼年强直性脊椎炎

目的：辅助诊断幼年强直性脊椎炎。方法：用ＰＣＲ技术对２４例临床表现为类风湿关节炎少关节型患儿的ＤＮＡ进行ＨＬＡ－Ｂ２７基因分析。结果：２４份标本中７例ＰＣＲ检测Ｂ２７基因阳性,占分析的２９．２％（７／２４）。７例Ｂ２７基因阳性病例中男５例,女２例,平均年龄１０．４岁。结论：Ｂ２７检测可作为诊断或鉴别诊断幼年强直性脊椎炎的重要指标,利于疾病病鉴别和预后估计。     

强直性脊柱炎患者HLA-B27位点等位基因相关抗原的表达

目的：探讨强直性脊柱炎（AS）患者HLA-B27位点等位基因相关抗原的表达。方法：采用补体依赖性微量淋巴细胞毒法检测418例脊柱关节炎（SpAS）患者和30例正常对照HLA-B27相关抗原。结果：418例SpAS患者73例被确诊为AS,Bw6、B27（47）、B27和B7/B27/B73/B81抗原阳性率分别为31%、28%、25%和22%。在AS中,B27阳性组与B27阴性组间有不同分布,两组B27（47）、B27、B7三种等位基因有统计学意义（P〈0.01）。在66例B27阳性组中,除B13与Bw6成负相关外,Bw4与B27（47）、B7与B27之间等均成明显的正相关。结论：在AS患者中,B13与Bw6、B60/61/47/48/81（13）,B7与B27,Bw4与B27（47）,Cw1与B42B45表达联锁失衡,B27并不是AS易感的唯一因素,其他基因位点可能起增强（如Cw1及Cw2）或抑制（如B13）AS发生的作用。     

HLA-B27抗血清筛选

<正>HLA-B27是人类白细胞B位点上的一个抗原,它与强直性脊柱炎（anky losing spondy litis,AS）的发病密切相关。国内外许多研究表明AS患者中95％以上为HLA-B27阳性,而正常人群中仅4％～6％左右为阳性。HLA-B27抗原检测现已作为临床诊断强直性脊柱炎的重要标志之一。目前国内大多数实验室仍采用血清学方法来检测B27抗原,因而制备一套特异性好,效价高的HLA-B27抗血清是至关重要的。我们在三年时间内收集了 3 000份产后血,进行筛选。     

HLA-B27检测与强直性脊柱炎的临床应用价值

目的通过检测人类白细胞抗原B-27（HLA-27）的表达,探讨其早期诊断与鉴别诊断在强直性脊柱炎（AS）中的临床应用价值。方法应用流式细胞术对146例AS患者,224例腰背疼痛患者及30例健康体检者外周血HLA-B27抗原进行检测,同时用魏氏法作红细胞沉降率（ESR）测定。结果146例AS患者中HLA-B27阳性136,阳性率91.89%,ESR（44.44±21.89）mm/h,224例腰背疼痛患者中HLA-B27阳性22例,阳性率9.82%,ESR（38.05±28.60）mm/h,30例健康体检者HLA-B27阳性2例,阳性率6.67%,ESR（7.37±3.44）mm/h。结论HLA-B27与AS具有高度相关性。对于长期不明原因的腰背疼痛和ESR增高的患者,HLA-B27的检测有助于AS早期诊断和与其它关节性疾病的鉴别诊断。     

强直性脊柱炎患者MICA基因第2、3和4外显子的多态性及其与HLA-B抗原的连锁不平衡

目的探讨皖籍汉族人群MICA基因（major histocompatibility complex class Ⅰchain-related gene A，MICA）第2、3、4外显子的多态性，及其与HLA-B抗原的连锁不平衡在强直性脊柱炎（ankylosing spondylitis，AS）发病中的作用。方法采用聚合酶链反应-序列特异性寡核苷酸探针杂交（polymerase chain reactionsequence-specific oligonucleotide probing，PCR-SS0）技术对56例AS患者和112名正常对照人群进行MICA基因第2、3、4外显子的多态性和HLA-B抗原的检测。结果AS患者和正常对照人群的MICA等位基因分布均以MICA＊008占优势，频率分别为32．14％和30．36％。两组人群MICA＊007等位基因的分布差异有统计学意义（X^2=10．18，P〈0．05，RR=2．50）。单倍型分析显示，AS患者和正常对照人群的MICA等位基因均显示出与多个HLA-B位点的连锁不平衡现象，两组间差异有统计学意义的单倍型为MICA＊007-B27（X^2=18．46，P〈0．05，RR=7．47）。分层分析结果显示，HLA-B27阳性与AS的相关性有统计学意义（P〈0．05），但MICA＊007基因与AS的相关性无统计学意义（P〉0．05）。结论AS患者中MICA＊007等位基因频率的显著升高可能源于MICA基因与HLA-B位点间的广泛连锁不平衡。     

HLA—B27亚型及其与强直性脊柱炎关系的研究进展

强直性脊柱炎（AS）是与HLA关联最强的疾病。HLA－B27由22个以上同种异型基因型（亚型：B*2701-B*22)组成，不同亚型核苷酸序列之间只存在个别位点的差异，其亚型具有分布不同的种族和人种流行情况，以B＊2705分布最广。近年来建立了大量的AS动物模型，人类B27转基因鼠实验证实B27分布是AS的原发关联成分，这种带有B27等位基因的实验动物可发生类似人类AS疾病。目前倾向于关节源性肽假说来解释HLA－B27在AS发病中的作用。     

采用 PCR-SSP法检测HLA-B27基因

目的：建立顺序特异引物聚合酶链反应（ＰＣＲ－ＳＳＰ）方法检测ＨＩＡ－Ｂ２７基因并与血清学方法比较。方法：设计合成Ｂ２７特异物３个和内源性阳性对照２个,建立ＰＣＲ－ＳＳＰ方法,用于Ｂ２７基因分型。血清学分型为一步法单克隆抗估方法。临床样本１００份,不源于可疑强直性脊柱炎患者。快速酚氯仿法提取模板ＤＮＡ。结果：１００例临床样本ＰＣＲ－ＳＳＰ行Ｂ２７基因分型均获成功。总耗时４ｈ。其中Ｂ２７阴性５８例,阳     

HLA-B27亚型及其与强直性脊柱炎关系的研究进展

强直性脊柱炎(AS)是与mA关联最强的疾病.HLA-B27由22个以上同种异型基因型(亚型B*2701～B*22)组成,不同亚型核苷酸序列之间只存在个别位点的差异,其亚型具有分布不同的种族和人种流行情况,以B*2705分布最广.近年来建立了大量的AS动物模型,人类B27转基因鼠实验证实B27分子是AS的原发关联成分,这种带有B27等位基因的实验动物可发生类似人类AS疾病.目前倾向于以关节源性肽假说来解释HLA-B27在AS发病中的作用.     

TAP polymorphism is not associated with ankylosing spondylitis and complications with acute anterior uveitis in HLA-B27-positive Japanese

Abstract: HLA-B27 is associated with the etiology of ankylosing spondylitis (AS) and acute anterior uveitis (AAU). Transporter associated with antigen processing (TAP) 1 and TAP2 polymorphism influences the range of peptide presented by HLA class I molecules. In this report, contribution of TAP polymorphism to the susceptibility to AS and AAU was studied in HLA-B27-positive Japanese individuals. Patients were classified into three groups: 16 AS patients, 14 AAU patients and 22 patients with both AS and AAU. Twelve HLA-B27-positive healthy individuals were included as a control. TAP polymorphism was detected by PCR-RFLP methods. Significant differences in frequencies of TAP1 alleles were not found between patient groups. None of the TAP2 frequencies showed increased or decreased frequencies compared with HLA-B27-positive healthy controls. In comparison with a random Japanese control, TAP2D allele frequency was significantly increased in the AAU group, but failed to reach a significant level in a group consisting of the AAU-only patients and the patients with both AS and AAU. All of the patient groups were noted to have a significantly increased prevalence of the TAP2H allele as compared to random controls; however, the higher frequency of this allele was detected in HLA-B27 healthy controls as well. These observations suggest a linkage disequilibrium between TAP2D, TAP2H and HLA-B27 in Japanese.     

HLA-B27 polymorphism and worldwide susceptibility to ankylosing spondylitis

HLA-B27 is strongly associated to ankylosing spondylitis (AS) and represents a family of eleven B27 alleles (B*2701–11). Our aim was to analyze the distribution of B27 subtypes by PCR/SSOP and genomic sequencing in a large group of populations ( n =17). 711 B27-positive samples from Caucasoid, Asian, African, Amerindian and Polynesian populations were selected to ascertain transracial gene mapping of the B27 subtypes. 476 of these were AS patients, chosen to investigate the contribution of B27 alleles to AS susceptibility. Some significant new findings have arisen from this study: 1) B*2705 was the predominant subtype in circumpolar and subarctic areas. B*2702 was found to be practically restricted to Caucasian populations, showing a higher frequency in Middle-East (Jews) and North Africa (Arabs/Berbers) groups. 2) B*2703 appears associated with AS in Western Africans. This is of remarkable interest since it was suggested that B*2703 would be negatively disease-associated. 3) Although B*2706 appears negatively associated with AS in Thais, we identified two patients from northern China carrying it. This may be a reflection of a disease heterogeneity and could indicate that more than one pathogenic agent can be involved in AS. B*2709 has been recently described as negatively associated with AS in Sardinians. The molecular changes His 114Asp (B*2706) and Asp 116His (B*2709) could modify the genetic susceptibility to AS.     

HLA-B27 and ankylosing spondylitis: tales from China

Abstract
The two most frequent HLA-B27 subtypes worldwide are B*2704 and B*2705. In the Han population of China B*2704 and, to a lower extent, B*2705 are found with significant frequency, and both are associated to ankylosing spondylitis (AS). Two articles in this issue report that the association to AS in this ethnic group is stronger for B*2704 than for B*2705. Thus, at least among the Han, B*2704 would be the strongest known susceptibility factor for AS.     

HLA-B27 subtypes in Asian patients with ankylosing spondylitis Evidence for new associations

Abstract: The aim of this study was to investigate the contribution of the different B27 subtypes to ankylosing spondylitis (AS) susceptibility. The polymerase chain reaction (PCR) in combination with the sequence-specific oligonucloetide probes (SSOs) was used to analyse the polymorphism in exon 2 and 3 of HLA-B27 in two Asian groups with different genetic HLA structures: Indian (I) and Thai (T) populations. The same number of AS patients (45) and healthy B27 positive donors (n=17) from both populations were analysed in order to ascertain the B27 subtypes. Three different findings can be concluded from this study: 1) B*2707 has been found to be associated with AS in both populations. This association has not been previously reported in either ethnic group. 2) B*2704 is strongly associated with AS in the Thai patients (91% in AS vs. 47% in C; RR=11.5; EF=0.83). In contrast, B*2704 was found with similar frequency in Asian Indians AS patients and controls (41% in AS vs. 41% in G). 3) B*2706 was found overrepresented in control populations and absent in AS patients (0% in AS vs. 47% in C; p_c<10^-6) showing the maximum value of protective fraction (PF=1). The B*2706 negative association with AS has not been previously described in other ethnic groups and could indicate a protective effect of this subtype on AS susceptibility. The B*2706 allele has two changes relative to B*2704 at residue 114 (His to Asp) and 116 (Asp to Tyr) in the pockets D/E. The importance that these differences can play in the pathogenesis of AS are discussed.     

Predominant association of HLA-B*2704 with ankylosing spondylitis in Chinese Han patients

Abstract
The HLA-B27 subtypes have a varied racial and ethnic prevalence throughout the world. However, the association of B27-subtypes with ankylosing spondylitis (AS) in the mainland China is unknown. To determine the association of B27-subtypes with AS in the Mainland Chinese Han population, a total of unrelated 153 patients with AS were enrolled in a large case-control association study, and 1545 unrelated, healthy, ethnically matched blood donors were included as controls. The genotyping of B27 and its subtypes was performed using the polymerase chain reaction with sequence specific primers (PCR-SSP). A total of 130 (84.97%) AS patients and 61 (3.95%) healthy controls were B27 positive. Three B27-subtypes, B*2704, B*2705 and B*2710, were further identified, of which both B*2704 and B*2705 were strongly AS associated. B*2710 was only detected in one AS patient and two other healthy controls. Considering only B27-positive cases and controls, a statistically different frequency of B27-subtypes was observed, with an over-representation of B*2704 ( P = 0.018). B*2704 was clearly more strongly associated than B*2705 with AS [odds ratio (OR ) = 2.4, P = 0.011]. Furthermore, a combined analysis including three previous studies of B27-subtype distributions in Chinese AS cases confirmed the stronger association of B*2704 with AS than B*2705 (OR = 2.5, P = 0.00094).     

A single-nucleotide polymorphism marker within the FCRL5 gene and HLA-B27 positive Han Chinese ankylosing spondylitis patients

The aim of this study was to determine whether FCRL5 genes in concert with human leukocyte antigen-B27 (HLA-B27) genotypes are associated with susceptibility to ankylosing spondylitis (AS) in Chinese population. One hundred and sixty-nine HLA-B27-positive AS patients (107 males and 62 females) and 184 HLA-B27-positive matched controls (112 males and 72 females) were analyzed from Han Chinese populations by case–control design, and their samples were genotyped using a panel of two single-nucleotide polymorphism (SNP) markers (rs6427384, rs12036228) within the FCRL5 gene by ligase detection reactions (LDRs) and the HLA-B27 subtypes were determined by polymerase chain reaction (PCR) using sequence-specific primer (SSP) methods. Our results show that in addition to B27 , the SNPs rs6427384 and rs12036228 were associated with AS, and the C-T haplotype was higher in cases with AS than in the control population [74.8% vs 63.6%, Fisher's P = 0.003, odds ratio (OR) = 1.660,95% confidence interval (CI) = 1.184−− 2.326]. Our results suggest that, in addition to HLA-B27 , a novel polymorphism within the FCRL5 gene confers susceptibility to AS in Han Chinese population.     

Susceptibility to ankylosing spondylitis is independent of the Bw4 and Bw6 epitopes of HLA-B27 alleles

We have characterized HLA-B27 alleles in a sample of the population from the Azores (n=46) with the aim of investigating the contribution of different subtypes to ankylosing spondylitis (AS). The study was carried out using PCR-SSOP and in some samples genomic sequencing was conducted. Some significant new finding have arisen from this study. First, B*2705,B*2702,B*2703,B*2707 and B*2708 alleles were found to be represented in this population. The polymorphism of B27 alleles found in a sample of the population from the Azores is higher than the Caucasian groups described. B*2703 and B*2707 have not previously been described to be represented in Caucasians and this could indicate admixtures with different populations of the world. In addition, the B*2708 allele was found to be associated with AS in a large family from the Azores. This association has not been previously reported in either ethnic group and needs to be confirmed in other population studies. This is of considerable interest since has only been described as a rare subtype underrepresented in the British population and has not been previously found to be associated with AS. B*2708 carries the sequence specifying the Bw6 epitope in contrast to most B27 alleles which carry a Bw4 sequence. Differences in this region (residues 77-83) can alter the F-pocket and affect T-cell recognition. The importance that these molecular changes can play in the pathogenesis of AS is discussed.     

Frequency of HLA-B27 subtypes in a Danish population and in Danish patients with ankylosing spondylitis

Polymerase chain reaction in combination with sequence-specific oligonucleotide probes were used to analyze nine HLA-B27 subtypes among 51 healthy I HLA-B27 positive Danish blood donors and 30 Danish HLA-B27 positive patients with ankylosing spondylitis (AS). In the group of healthy Danes we found two subtypes, B*2705 (90.2%) and B*2702 (9.8%), however, among the AS patients only the B*2705 subtype was detected. We did not find a significant evidence for associations between AS and a particular HLA-B27 subtype in a Danish population.