中国汉族强直性脊柱炎患者人类白细胞抗原-B27多态性研究

目的 本研究拟利用最新的人类白细胞抗原(HLA)-B27亚型数据,调查中国汉族强直性脊柱炎(AS)患者HLA-B27及其亚型的分布情况.方法 从我院脊柱关节炎患者数据库中随机抽取100例AS患者.用luminex液态芯片,结合聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)技术对HLA-B位点作低分辨分型.HLA-B27阳性者进一步用聚合酶链反应-序列特异性引物(PCR-SSP)法做高分辨HLA-B27亚型检测.结果 经随机抽样纳入无关AS患者98例,其中HLA-B27阳性93例,阳性率94.9%,其中B*2704亚型76例(81.7%),B*2705亚型12例(12.9%),B*2715亚型5例(5.4%).与另外2篇文献报道的HLA-B27阳性汉族健康人群比较,没有一致的证据表明HLA-B27亚型分布在AS患者和健康人群中存在差异.但这2项汉族健康人群中的研究均未发现B*2715亚型.结论 中国汉族AS患者B27亚型以B*2704为主,其次是B*2705.B*2715作为一个频率极低的等位基因,本组病例中发现5例,提示B*2715与AS发病存在关联.     

HLA-B*27及其亚型与强直性脊椎炎的相关性研究

目的:探讨人类白细胞抗原B*27(HLA-B*27)及其亚型与强直性脊柱炎(AS)患者发病的相关关系。方法:采用二重Taqman实时PCR方法检测23名AS就诊患者及其105名一级亲属的HLA-B*27,并采用高分辨的PCR-SSP技术分析HLA-B*27的亚型。结果:AS就诊患者HLA-B*27的阳性率为91.30%,其一级亲属HLA-B*27的阳性率为42.85%,患病率22.86%;3个家系的HLA-B*27亚型为HLA-B*2705,其他家系均为HLA-B*2704。结论:AS的发生与HLA-B*27密切相关,且具有家族遗传性;与HLA-B*2705比较,HLA-B*2704是发生AS更危险的因素。     

HLA-B27亚型与强直性脊柱炎的相关性研究

目的:研究重庆地区汉族人群的正常人和强直性脊柱炎(AS)患者的HLA-B27亚型基因分布的特点,分析HLA-B27亚型与AS发生的相关性.方法:采用PCR-SSP方法对重庆地区汉族人群中HLA-B27阳性的正常人126例和AS患者134例进行HLA-B27亚型的检测.结果:在正常组和AS组中,共检出了10种HLA-B27亚型,2组均以B*2704和B*2705亚型为优势亚型,2亚型分别为90%和95%.2组间的B*2704和B*2707亚型的构成比差异有统计学意义.B*2704亚型在AS患者组中的分布大于正常组,B*2707亚型在正常组的分布大于AS患者组.结论:B*2704亚型与AS呈正相关(OR=2.12,P＜0.05),为重庆地区汉族人群中的主要致病基因,而B*2707亚型与AS呈负相关(OR=0.11,P＜0.05),可能有保护性作用.     

人类白细胞抗原-B*2704/B*2705重链拮抗肽的筛选和初步鉴定

目的 从噬菌体展示随机12肽库筛选人类白细胞抗原(HLA)-B·2704及B·2705重链拮抗肽并做初步鉴定.方法 用HLA-B*2704/B*2705重链胞外区蛋白分别筛选噬菌体展爪随机肽库,酶联免疫吸附试验(ELISA)鉴定阳性克隆,DNA测定确定氨基酸序列,免疫荧光和流式细胞术鉴 ,定噬菌体克隆分别与HLA-B*2704及B*2705细胞株结合的特异性.结果 经3轮筛选,获得12个HLA-B·2704拈抗肽,共有5种序列,分别为HTSFCSTHLCLI(×4),QHCSPTLCQIHR(×5),ARCTITL-CYLSN(×1),YGLCTDWYCHIT(×1),YPLCDAILCRLP(×1);10个B*2705拮抗肽共有4种序列,分别为:①SHCSPHWCALPF(×6);②HLCSNSLCLLPW(×2);③EPMCSWFWCTLP(×1);④WTCSPLLCTWGA(×1).比对分析表明,B*2704与B*2705拮抗肽的序列是基本一致的,均含有CS(T)TXXL(W)CXL表位.展示有B*2704拮抗肽的噬菌体克隆可与HLA-B*2704细胞株结合,阳性率为43.55%;而B*2705拈抗肽噬菌体克隆与HLA-B·2705细胞株的阳性结合率为45.69%.结论 筛选获得的HLA-B27拈抗肽的噬菌体克隆具有一定的亲和力,可与表达于细胞株表面的B*2704和B**2705分子特异性结合,而与正常B细胞不结合,因而表现出一定的结合特异性.     

类风湿关节炎合并骶髂关节改变患者临床特点分析

目的 提高对类风湿关节炎合并骶髂关节改变的认识。方法 收集13例合并骶髂关节改变的类风湿关节炎患者及67例不合并骶髂关节改变的类风湿关节炎患者的临床和实验室检查资料，并加以分析比较。结果合并骶髂关节改变的类风湿关节炎患者，以男性为主，多以桡腕关节炎首发，下肢关节大多呈非对称性炎症改变，人类白细胞抗原(HLA)-B27阳性，或同时伴有类风湿因子(RF)阳性。结论 类风湿关节炎患者如出现臀部和／(或)下背部症状，要考虑合并骶髂关节改变，可做HLA-B27和骶髂关节CT检查。     

肠病性关节炎30例临床特征分析并文献复习

目的 通过分析炎性肠病伴发关节炎的临床特征,提高对其的认识,以及探讨其与HLA-B_(27)的相关性.方法 分析30例炎性肠病(溃疡性结肠炎、克罗恩病)伴发脊柱关节病变的临床表现、实验室检查及x线表现.结果 肠病性关节炎患者30例,男14例,女16例.出现肠道表现的年龄16～48(32.2 ±11.0)岁,病程1个月～20(5.9±3.4)年,出现关节炎的年龄15～52(43.4±6.8)岁,出现肠道表现与关节炎或发生腰背痛的时间间隔为0～13(4.2±4.0)年.26例患者外周关节受累,其中14例的表现极似类风湿关节炎;22例患者腰背痛,其中7例HLA-B_(27)阳性,且13例患者有影像学骶髂关节病变.关节外的表现包括:24例发热,6例肌腱端炎,4例眼炎,l例腊肠趾.9例患者HLA-B_(27)阳性.结论 炎性肠病相关的关节炎表现复杂多样,可表现为多关节对称性受累、单或寡关节和(或)中轴关节受累,肠病性关节炎骶髂关节受累与HLA-B_(27)相关.     

不同亚型银屑病关节炎的临床特征和实验室指标

目的分析不同亚型银屑病关节炎(PsA)临床特征、实验室指标的差异,以提高对该疾病的认识,为临床诊疗提供借鉴。方法对中国人民解放军264医院2005年1月至2011年12月住院诊治的PsA患者进行分型,并对不同亚型PsA患者首发症状、受累关节、类风湿因子(RF)、抗环瓜氨酸多肽抗体(抗CCP抗体)、人类白细胞抗原-B27(HLA-B27)进行比较分析。结果 82例PsA患者,皮疹先发于关节炎者60例(73%),皮疹和关节炎症状1个月内同时出现者9例(11%),关节炎先发于皮疹者13例(16%)。PsA临床分型:远端指(趾)间关节炎型10例(12.2%)、残毁型关节炎型6例(7.3%)、对称性多关节炎型19例(23.2%)、非对称性寡关节炎型20例(24.4%)、脊柱关节炎型27例(32.9%)。红细胞沉降率、C反应蛋白在PsA各亚型之间比较,差异无统计学意义(均P>0.05)。对称性多关节炎型RF或抗CCP抗体的阳性率为68%,远高于脊柱关节炎型(P<0.05)。脊柱关节炎型HLA-B27阳性率为37%,远高于远端指(趾)关节炎型、对称性多关节炎型、非对称性寡关节炎型(均P<0.05)。结论 PsA多以皮疹为首发,仍有部分患者以关节炎首发。临床分型以脊柱关节炎型多见。RF阳性或抗CCP抗体阳性PsA患者易出现对称性多关节受累,HLA-B27阳性PsA患者易出现中轴关节受累。     

磁共振成像对早期骶髂关节炎的诊断价值研究

目的了解磁共振成像(MRI)在早期骶髂关节炎诊断中的意义。方法对82例炎症性腰背痛或不对称性下肢滑膜炎患者的骶髂关节CT扫描、MRI平扫以及病理检查结果进行分析比较。结果45例病理证实的早期骶髂关节炎中,69%(31/45)MRI显示骶髂关节存在炎症性改变。但17例病理检查骶髂关节无炎症性改变者,也有59%(10/17)MRI表现不同程度骶髂关节炎症性改变。以病理检查结果为依据,MRI对早期骶髂关节炎诊断的敏感性、特异性分别为69%和41%。结论MRI对早期骶髂关节炎的诊断有一定的敏感性,但特异性不高,临床应用要慎重考虑。     

晚发型脊柱关节病的临床特征分析

目的 总结晚发型脊柱关节病(SpA)的临床特点,以期提高对本病的诊治水平.方法 分析56例晚发型SpA患者的临床、实验室及放射学资料,并与62例中青年发病的SpA患者进行比较.结果 晚发型SpA组,以外周关节起病者和起病时有下肢炎性凹陷性水肿患者显著多于中青年发病SpA组[86%(48/56)比47%(29/62)和43%(24/56)比8%(5/62),均P<0.01];而中青年发病SpA组在发病初即有腰背痛的患者显著多于晚发型SpA组[45%(28/62)比13%(7/56),P<0.01].随着病程的进展,晚发型SpA组出现外周关节炎的患者显著多于中青年发病SpA组[96%(54/56)比81%(50/62),P<0.01];而中青年发病SpA组出现腰背痛的患者显著多于晚发型SpA组患者[74%(46/62)比20%(11/56),P<0.01].晚发型spA组,关节外表现如发热显著多于中青年发病SpA组(P<0.01)、肌腱端炎及色素膜炎亦显著多于中青年发病SpA组(均P<0.05).晚发型SpA组和中青年发病的SpA组HLA-B27的阳性率分别为86%和82%,两组比较无显著性差异(P>0.05).血沉和C反应蛋白,晚发型SpA组均显著高于中青年发病SpA组(均P<0.01).中青年发病SpA组出现骶髂关节炎的患者显著多于晚发型SpA组患者[71%比21%,P<0.01].结论 晚发型SpA和中青年发病的SpA均以男性多发,HLA-B27阳性率相近;但晚发型SpA较中青年发病的SpA有更多的外周关节炎、更广泛的下肢炎性凹陷性水肿及更多关节外表现,而中青年发病SpA则有更多腰背痛和X线证实的骶髂关节炎表现.     

沙利度胺致不完全性结肠梗阻一例

患者女,45岁.因腰骶疼痛伴晨僵4年,加重1个月入院.患者2002年出现双侧腰骶部疼痛,在外院查人类白细胞抗原(HLA)-B27阳性,骶髂CT示骶髂关节炎.外院诊断考虑强直性脊柱炎(AS),治疗予柳氮磺吡啶、沙利度胺25 mg/d.     

HLA-B27 subtypes in Turkish patients with ankylosing spondylitis and healthy controls

The aim of this study was to determine human leukocyte antigen (HLA)-B27 subtypes frequency in ankylosing spondylitis (AS) and related spondyloartropathy (SpA) patients. Therefore, we investigated the differences in HLA-B27 subtypes between HLA-B27-positive patients and controls. Sixty six patients were included in this study (51 AS and 15 SpA). Thirty-five individuals were diagnosed with leukemia or chronic renal failure, and their donors without any rheumatological problem (no SpA history) were selected as the control group. HLA-B27 subtyping was performed by PCR-SSP (polymerase chain reaction with sequence-specific primer) method in serologically HLA-B27-positive 46 AS patients, 9 SpA patients and control group. When the frequency of HLA-B27 was 4.5% in Turkish population, this frequency was 90.2% in AS patients. Four different HLA-B27 subtypes found in AS patients were B*2705 (65.2%), B*2702 (26.1%), B*2704 (6.5%) and B*2707 (2.2%). In SpA patients, B*2705 and B*2702 found in equal frequency. Five B27 alleles were identified in our control group: B*2705 (54.3%), B*2702 (31.4) %, B*2703 (2.9%), B*2704 (2.9%) and B*2702/B*2705 (8.5%). Both in the patient group and in the control group, we also observed B*2705 as most frequent allele, and B*2702 was second common allele. Our results show that the frequency of HLA-B27 subtypes is not significantly different between patients and controls (P?>?0.10).     

The association of HLA-B*27 subtypes with ankylosing spondylitis in Wuhan population of China

The aim of this study was to investigate the association of the B27 subtypes with ankylosing spondylitis (AS) in the Wuhan population of China. We selected 317 HLA-B27-positive individuals (145 controls and 172 patients with ankylosing spondylitis). The B27 subtypes were characterized using a PCR-SSP method. Six B27 subtypes were determined: B*2702, 03, 04, 05, 06 and B*13. HLA-B*2704 and HLA-B*2705 were the two high frequency genotypes in controls and patients. Compared with the controls, the AS patients had high frequency of B*2704 (patients 69.2% vs. controls 53.8%) and low frequency of B*2705 (patients 23.8% vs. controls 33.1%). B*2703 was detected in 10 (5.8%) patients and in 13 (8.9%) controls. B*2702, 06 and B*2713 were relatively rare. Our results show that the allele conferring risk to AS in the Wuhan population of China was B*2704 and B*2705. B*2704 is strongly associated with AS.     

Subtypes of the HLA-B27 molecule and association with spondylarthropathies

HLA-B27 subtypes differ in their ethnic distribution and in their susceptibility to spondylarthropathies (SA). B*2705 and B*2702 are the most frequent disease-associated subtypes in Caucasians as well as B*2704 and B*2707 in Asia while B*2706 in Asia and B*2709 in Sardinia have been reported not to be associated to SA. Differences in antigenic peptide presentation could underlie such behavior. Several studies suggested that a Tyr C-terminal peptide anchor could be found preferentially in disease-associated subtypes and could be therefore one of the criteria in the search of putative arthritogenic peptide(s). We analyzed by HPLC and Edman sequencing peptides eluted from immunopurified HLA-B27 molecules expressed on B-lymphoblastoid cell lines or C1R transfectans of human origin. We focused our work on B*2707, associated with SA in the same geographical area where B*2706 is not. We found the same preference for Leu at the C-terminus in the peptides bound by both subtypes without any significant signal for Tyr. In the same experimental conditions a Tyr C-terminal anchor was found for B*2705, B*2702, B*2704, B*2703 and also for B*2701 and B*2708, 2 rare subtypes for which binding specificity was previously unknown. Comparison of the F-pocket aminoacid composition in these various subtypes showed a correlation between Asp at position 116 and Tyr at the peptide C-terminus. Asp116 is changed for Tyr in B*2706, B*2707 and His in B*2709, all subtypes allowing a Leu C-terminal anchor. Therefore a Tyr C-terminal anchor correlates with the HLA-B27 F-pocket composition rather than with susceptibility to SA.     

Prevalence of HLA-B27 and subtypes of HLA-B27 associated with ankylosing spondylitis in Galicia, Spain

OBJECTIVE: To assess the prevalence of HLA-B27 and its subtypes in both the normal population and in patients with Ankylosing Spondylitis (AS) in Galicia, Northwest Spain. METHODS: The prevalence of HLA-B27 in the normal population was determined by checking the number of HLA-B27 positive samples in 308 subjects from different areas of Galicia who had donated organs over a period of 4 years. A total of 106 patients with the diagnosis of AS, according to the modified New York clinical criteria for definitive ankylosing spondylitis, were collected from three very representative areas of Galicia. HLA-B27 was determined by PCR using the primers E91s and E136as, while 11 subtypes of HLA-B27 were analyzed using a commercial kit. RESULTS: The prevalence of HLA-B27 in organ donors was 9.34%. HLA-B27 was present in 94.3% of patients with AS. Subtypes B*2701, B*2709 and B*2710 were not found. The subtypes found in the normal population were; B*2705 (79.5%), B*2702 (18%) and B*2708 (2.5%). The subtypes associated with AS were B*2705 (88%) and B*2702 (12%). CONCLUSION: The prevalence of HLA-B27 in Galicia was 9.34%, which is higher than previously published in Spain. The frequency of the subtypes associated with AS was similar to that reported for other Spanish regions.     

Correlation of HLA B27 subtypes with clinical features of ankylosing spondylitis

Aim: The aim of the present study was to identify the B*27 subtypes associated with ankylosing spondylitis (AS) in our population and correlate them with clinical features of AS. Method: Whole blood samples were collected from 81 HLA‐B27 positive AS patients and 29 controls (asymptomatic healthy unrelated individuals) positive for HLA‐B27. Clinical details of the patients were recorded which included history of inflammatory back pain, sacroiliitis, spine involvement, enthesitis, peripheral arthritis and uveitis. HLA‐B27 subtypes were detected using commercially available techniques. Fisher’s exact test was used for statistical analysis. Results: The subtypes observed in AS patients were B*2705 (67.9%, 55/81), B*2704 (28.4%, 23/81), B*2707 (2/81) and B*2702 (1/81). Subtypes in the controls were B*2705 (62.07%, 18/29), B*2707 (27.59%, 8/29) and B*2704 (10.34%, 3/29). Uveitis was observed more in B*2704‐positive AS patients (34.78%, 8/23) compared to B*2705‐positive AS patients (16.36%, 9/55). However, the difference was not statistically significant (P = 0.130). No major differences were found between B*2705 and B*2704 for other clinical features. Conclusion: B*2705 was the main subtype observed in both patient and control groups. Frequency of B*2704 was more in AS patients compared to controls. Occurrence of AS‐associated uveitis was more often in B*2704‐positive AS patients compared to B*2705‐positive ones.     

Distribution of HLA-B*27 Alleles in Pa-tients with Ankylosing Spondylitis in Iran

Background: HLA-B*27 is strongly associated with ankylosing spondylitis (AS). It represents a family of alleles that differ among ethnic groups. Objective: The aim of this study was to determine the distribution of HLA-B*27 alleles in AS patients and healthy controls in Isfahan (Iran). Methods: Sixty AS patients and 430 healthy blood donors were selected. All subjects were HLA-B*27 positive by flow cytometry. HLAB* 27 subtypes were determined by PCR-SSP. Results: Forty patients (66.7%) and 17 controls (3.95%) were HLA-B*27 positive. Subtypes detected by PCR-SSP were B*2705, B*2702, B*2704 and B*2707. One patient was B*2702/B*2710. No significant difference was found in the distribution of these alleles between AS patients and controls. Conclusion: Although Caucasian subtypes are predominant among Iranians, this population is characterized by a combination of both specific Caucasian and Oriental subtypes. However such results should be interpreted carefully because of the small sample size in our investigation and definitive conclusion awaits more ethnicgroup studies.     

Human leukocyte antigen-B*2705 is the predominant subtype in the Korean population with ankylosing spondylitis,unlike in other Asians

This study was performed to investigate the frequency of human leukocyte antigen (HLA)-B27 subtypes in the Korean population with spondyloarthropathy (SpA). We determined the HLA subtypes of 267 SpA patients who were positive for the B27 antigen (as determined by serology) by using a PEL-FREEZ kit (Dynal Biotech, Wisconsin, USA). Clinical features, including sex, peripheral joint involvement, and the presence of uveitis, were analyzed in a retrospective cohort study. Among 267 patients, 244 were B*2705-positive and 22 were B*2704-positive. One patient was positive for B*2704/2705. No other subtype was observed among the analyzed patients. We found that HLA-B*2705 was the predominant subtype in Koreans with SpA; this finding is remarkable because other Asians such as the Han or the Japanese exclusively have the B*2704 subtype. This result suggests that the clinical features and prevalence of SpA in Koreans may be similar to those observed in Europeans.     

Distribution of HLA-B27 and its alleles in patients with reactive arthritis and with ankylosing spondylitis in Tunisia

The purpose of the present study is to investigate the frequency of HLA-B27 and its alleles in reactive arthritis (ReA) and in ankylosing spondylitis (AS) in Tunisia. HLA-B27 alleles were typed by PCR amplification with sequence-specific primers. We studied 17 patients with ReA associated with urethritis or with gastrointestinal infection; 42 HLA-B27-positive patients with AS and 100 healthy controls. Eleven ReA patients (67.7%) were HLA-B27 positive. There was an increased frequencies of HLA-B27 (P = 7.76 × 10⁻¹², OR = 59.30) and a moderate increase of HLA-B51 (P = 0.015; OR = 4.91) alleles in ReA patients when compared with healthy controls. Four B27 subtypes were identified: B*2702, 05, 09 and B*2712. The distribution of these alleles in the ReA patients was 37.5% for B*2702 and B*2705. Only these two subtypes were detected in 18 (42.8%) and 24 (57.1%), respectively, of the AS patients. B*2709 and B*2712 were relatively rare in ReA patients and were identified in one case each. Our results showed a restricted number of HLA-B27 subtypes associated with ReA and AS. B*2702 and 2705 were common in ReA and AS patients.