人类白细胞抗原与急性前葡萄膜炎的相关性

目的:探讨急性前葡萄膜炎(acute anterior uveitis,AAU)与人类白细胞抗原(human leucolyte antigen,HLA-B27)的相关性。方法:应用聚合酶链反应(sequence special prime polymer-ase chain reaction,SSP-PCR)基因检测技术,对AAU患者进行HLA-B27基因检测,观察HLA-B27阳性与阴性AAU临床特征并加以分析。结果:在36例AAU患者中,HLA-B27抗原阳性29例,阳性率81%,37例健康对照组,阳性9例,阳性率24%,两者有显著性差异(χ2=23.12,P<0.01)。结论:HLA-B27与AAU明显相关,HLA-B27阳性与阴性患者有一定程度的差异,常伴有全身脊柱关节病,采用SSP-PCR基因检测技术测定HLA-B27快速、简单、准确性高、客观性强,值得推广应用。     

急性前葡萄膜炎的HLA-B27阳性与阴性患者的临床对比

目的:用微量淋巴细胞毒试验对急性前葡萄膜炎(acuteanterioruveitis,AAU)HLA-B27抗原基因进行检测,观察HLA-B27阳性与阴性患者的临床特征有无差异及临床意义。方法:用微量淋巴细胞毒试验对100例AAU患者进行HLA-B27检测,并随机抽取20例阳性和20例阴性AAU患者进行临床特征观察。结果:在100例AAU患者中HLA-B27阳性64例,阴性36例,分别抽取的20例经比较,HLA-B27阳性患者多见于男性,单眼多见,以粉尘状KP,发病时视力下降明显,易复发,且并发症多为其特征,激素治疗效果佳。结论:对AAU患者进行HLA-B27检测,对评价葡萄膜炎的病因和预后有一定价值。HLA-B27阳性与阴性患者的临床特征有一定程度差异。     

人类白细胞抗原-B27相关性急性前葡萄膜炎病情与脉络膜厚度变化的关系

目的　探讨人类白细胞抗原（human leukocyte antigen,HLA）-B27相关性急性前葡萄膜炎（acute anterior uveitis,AAU）病情与脉络膜厚度变化的相关性。方法　HLA-B27 相关性AAU患者32例32眼及其对侧眼被纳入本研究,除对患者进行眼底荧光血管造影（fluorescein fundus angiography,FFA）等常规检查外,利用光学相干断层扫描 （optical coherence tomography,OCT） 对患者双眼黄斑中心凹下脉络膜厚度（subfoveal choroidal thickness,SFCT）及黄斑中心凹视网膜厚度（central foveal thickness,CFT）进行测量。对比AAU患者治疗前后SFCT及CFT变化。结果　FFA显示,32眼HLA-B27相关性AAU患者视盘毛细血管均有荧光素渗漏 （100.0%）,其中13眼（40.63%）视网膜毛细血管荧光素渗漏 。OCT检测结果显示,在炎症急性期,32眼HLA-B27相关性AAU患者的黄斑区脉络膜血管扩张显著。HLA-B27 相关性AAU患眼的SFCT ［（342.54±70.71）μm］较对侧眼的SFCT［（283.41±79.15）μm］显著增加 （P=0.003）,AAU患眼的CFT［（281.46±56.42）μm］与对侧眼的CFT［（268.49±51.91）μm］比较,差异无统计学意义（P=0.342）。经治疗炎症消退后,AAU患眼的SFCT减少至（284.13±99.07）μm,与治疗前相比,差异有统计学意义（P=0.009）。结论　HLA-B27 相关性AAU患眼SFCT增加,脉络膜厚度可作为评估HLA-B27相关性AAU病情严重程度的指标之一。     

低相对分子质量多肽2基因多态性与急性前葡萄膜炎的关系

目的：评价低相对分子质量多肽2基因多态性与急性前葡萄膜炎的关系。方法：收集23例急性前葡萄膜炎患者及45例正常对照血样本,进行组织相关性抗原（HLA-B27）检测及低相对分子质量多肽2基因区的Cfo I限制酶位点多态性的研究。结果：低相对分子质量多肽2基因的纯合子BB在急性前葡萄膜炎患者中比正常对照者频率增高（P＜0.05),而与急性前葡萄膜炎是否复发及HLA-B27检测结果没有相关性（P＞0.05)。结论：低相对分子质量多肽2基因多态性与急性前葡萄膜炎发病存在明显相关。     

急性前色素膜炎与HLA—B27抗原的相关性

对52例急性前色素膜炎患者,50例健康人,19例其他色素膜炎患者进行HLA-B27抗原的测定,结果急性前色素膜炎患者HLA-B27抗原阳性率为60%,正常对照组为2%,说明HLA-B27为急性前色素膜炎的相关抗原。HLA-B27阳性的急性前色素膜炎患者与HLA-B27阴性的急性前色素膜炎患者的临床现象是不同的。     

强直性脊柱关节病伴发葡萄膜炎的临床研究

目的探讨HLA-B27与强直性脊柱关节病（As）伴发葡萄膜炎发病的关系。方法应用SSP-PCR对正常人和患者进行HLA-B27抗原进行研究，并对患者的临床特征、影像学检查加以分析。结果强直性脊柱关节病伴发葡萄膜炎患者和对照组HLA．B。阳性率分别80．56％和24．32％（χ^2=23．12，P〈0．01），两者比较差异有显著性，X线有轻重不等的骶髂关节改变。结论采用SSP-PCR基因检测技术测定HLA-B27，快速、简单、准确性高，值得推广应用。HLA-B27，与强直性脊柱关节病伴发葡萄膜炎的关系密切。对原因不明的葡萄膜炎患者进行HLA-B27及影像学检查有助于早期发现强直性脊柱炎。     

HLA-B27相关的前葡萄膜炎眼后节并发症的临床特点

目的探讨HLA—B27阳性的前葡萄膜炎眼后节并发症的临床特点及治疗。方法2002年1月至2005年10月就诊的前葡萄膜炎患者采用流式细胞术进行外周HLA-B27的检测，筛选出71-例82眼HLA-B27阳性前葡萄膜炎患者，分为两组：实验组为眼后节受累的患者24例31眼，对照组为眼后节未受累的患者47例51眼。另有HLA—B27阴性前葡萄膜炎患者74例116眼作参考。所有患者均进行裂隙灯、眼底镜等常规眼科查体，部分行眼底荧光血管造影。分析了HLA—B27相关的前葡萄膜炎眼后节并发症的临床特点。采用x^2检验及t检验进行统计学分析。结果71例82眼HLA—B27阳性前葡萄膜炎中有24例31眼占37．8％出现眼后节并发症者，包括：黄斑囊样水肿12例15眼占48．4％，视乳头水肿7例8眼占25．8％，而玻璃体炎最多见为21例27眼占87．1％，8例10眼占32．3％患者存在两种或两种以上的眼后节表现。74例116眼HLA—B27阴性者有8例12眼占10．3％有眼后节表现。实验组中发生前房成型纤维素渗出31眼中18眼占58．06％和积脓31眼中9眼占29．03％明显高于对照组（前房纤维素渗出51眼中3眼，5．88％，X^2=27．56，P〈0．01；前房积脓51眼中1眼，1．96％，X^2=13．20，P〈0．01）；实验组中伴发相关全身性疾病24例中有16例占66．67％的几率高于对照组（47例中有17例，31．66％，X^2=5．94，P〈0．05）。出现眼后节并发症的患者经全身及局部应用糖皮质激素治疗，31眼中有11眼最佳矫正视力≥1．0。结论HLA-B27阳性前葡萄膜炎易出现眼后节并发症，HLA—B27相关的前葡萄膜炎眼后节受累的患者发生相关全身性疾病和前房纤维素渗出与积脓的几率较高。     

并发性白内障术中前房注射曲安奈德的临床研究

目的探讨前房注射曲安奈德对前葡萄膜炎并发性白内障人工晶状体植入术后前房渗出的预防效果及安全性。方法将68例（68眼）前葡萄膜炎并发性白内障行白内障摘出人工晶状体植入术的患者随机分为两组：实验组34例,术中前房内注射曲安奈德2mg（0.05ml）;对照组34例,术中未注射曲安奈德。观察并比较两组术后前房渗出情况及角膜内皮细胞密度、眼压等指标。结果实验组术后前房渗出明显低于对照组,差异有统计学意义（P〈0.05）;曲安奈德对角膜内皮及眼压无明显影响。结论前房注射曲安奈德可减轻前葡萄膜炎并发性白内障人工晶体植入术后前房渗出,是一种安全有效的给药方法。     

人类白细胞抗原B27亚型基因与急性前葡萄膜炎的相关性研究

目的 探讨人类白细胞抗原B27亚型基因与急性前葡萄膜炎(acute anterior uveitis,AAU)易感性的关系。 方法 对49例临床确诊的AAU患者,通过聚合酶链反应(polymerase chain reaction, PCR)特异性扩增技术检测B27;以B27阳性者的DNA为模板对其人类白细胞抗原HLA-B的第二、三外显子片段扩增。采用DNA测序技术对扩增产物做基因序列分析,经计算机处理获得受检者HLA-B27亚型的信息。 结果 受检者中29例为B27阳性,占59.39%,其中仅发现B2704(13例,占44.00%)和B27052(16例,占56.00%)二种亚型基因携带者。二者间多数临床表现差异不大,但携带B27052基因的AAU患者伴发强直性脊柱炎(ankylosing spondylitis, AS)的人数(7人,占24.24%)显著高于B2704基因携带者(1人,占3.74%)。 结论 B2704和B27052单独的亚型特异性与AAU无易感性关联;但B27052基因可能与并发AS有关。 (中华眼底病杂志, 1999, 15:139-142)     

人类白细胞抗原-B27阳性急性前葡萄膜炎患者外周血中Th细胞亚群的表达及意义

背景人类白细胞抗原-B27（HLA-B27）阳性急性葡萄膜炎是非感染性葡萄膜炎常见的类型之一,Th17细胞是在人类自身免疫性疾病中发挥重要作用的细胞因子,而Th17细胞与HLA—B27阳性急性前葡萄膜炎的关系鲜见报道。目的研究HLA—B27相关性急性前葡萄膜炎患者外周血中辅助性T淋巴细胞亚群（Thl、Th2、Th17）的表达及意义。方法采用前瞻性队列研究设计。收集2011年1—10月于无锡第二医院眼科就诊的HLA—B27阳性急性前葡萄膜炎患者22例,并收集性别和年龄匹配的健康体检者16名作为正常对照组。采用流式细胞术检测受检者外周血中Thl、Th2、Th17细胞的表达比例,采用免疫比浊法检测患者外周血中c反应蛋白（CRP）质量分数,并对患者的病情程度进行评分,采用Spearman秩相关分析法对患者外周血中Thl、Th2、Th17细胞比例与病情严重程度评分或CRP质量分数的关系进行统计分析。结果HLA—B27阳性急性前葡萄膜炎患者外周血中-γ干扰素（IFN-γ）CD4＋Thl细胞比例、CD4＋白细胞介素-17（IL-17）＋Th17细胞比例均明显高于正常对照组,差异均有统计学意义[（23．11±9．69）％VS．（16．00±4．26）％,P=0．041;（3．96±2．92）％VS．（1．68±0．60）％,P=0．002],而CD4＋IL4＋Th2细胞比例与正常对照组相比差异无统计学意义[（0．33±0．36）％VS．（0．56±O．34）％,P=0．122]。患者外周血Thl细胞比例与患者病情严重程度评分及CRP质量分数均无明显相关性（r=0．197,P=0．500;r=0．253,P=0．383）;Th2细胞比例与患者病情严重程度评分及CRP质量分数均无明显相关性（r=0．068,P=0．817;r=0．439,P=0．116）;Th17细胞比例与患者病情严重程度评分呈明显正相关（r=0．805,P=0．001）,与患者CRP质量分数无显著相关性（r=0．226,P=0．436）。结论HLA—B27阳性急性前葡萄膜炎患者外周血中CD4＋T细胞内IFN-γ和IL-17细胞呈高表达,且Th17细胞比例与患者病情的严重程度有关,提示Th1细胞和Th17细胞共同参与了急性前葡萄膜炎的发病过程,可能以Th17细胞发挥作用为主。     

Acute anterior uveitis and HLA-B27 subtypes

The tissue antigen HLA-B27 is found in 50% of Dutch acute anterior uveitis (AAU) patients. The prevalence of HLA-B27 in the normal population is only 8%. However, only approximately 1% of HLA-B27+ individuals will develop AAU. Therefore, it is possible that the disease is associated with a particular B27 subtype. We typed lymphocytes of 36 B27+ AAU patients, of which 20 also had ankylosing spondylitis, for three serologically defined B27 subtypes (B27 W, B27 K and B27 non W/non K). These subtypes were normally associated with AAU. The subtype frequencies in the patients suffering from both AAU and AS also showed no preference for a certain subtype. Subtype-specific characteristics of the primary structure of the various B27 subtype molecules therefore cannot be responsible for the disease association.     

HLA-B27 typing in the categorisation of uveitis in a HLA-B27 rich population

AIMS: To determine whether HLA-B27 typing helps the clinician in the diagnostic examination of uveitis in a HLA-B27 rich population and also whether the clinical picture of HLA-B27 positive unilateral acute or recurrent anterior uveitis (AAU) is distinguishable from the idiopathic negative form. METHODS: During a 3 year period 220 consecutive patients with undetermined uveitis at onset were examined in the Helsinki University Eye Clinic. HLA-B27 antigen was tested for 85% of the patients. Other laboratory or x ray examinations were performed on the basis of the anatomical classification of uveitis and the biomicroscopic features characteristic of uveitis associated systemic diseases. RESULTS: HLA-B27 antigen was found significantly more often in patients with anterior (71%) and acute/recurrent unilateral (79%) uveitis than in patients with intermediate, posterior panuveitis (7%), and chronic (7%) or bilateral (12%) forms. Of the 16 cases of HLA-B27 negative unilateral AAU, five showed biomicroscopic features representing uveitis entities. The remaining 11 cases did not differ in any respect from the cases of HLA-B27 positive unilateral AAU. CONCLUSION: HLA-B27 antigen helps the clinician in the diagnostic examination of unilateral AAU. Positive test results serve as a clue to search for spondyloarthropathies, and negative results indicate the need to look for specific uveitis entities and other systemic diseases. The occurrence of HLA-B27 positivity in conjunction with uveitis entities other than unilateral AAU is of the same level or less than in the population of Finland in general.     

The lifetime cumulative incidence of acute anterior uveitis in a normal population and its relation to ankylosing spondylitis and histocompatibility antigen HLA-B27

The lifetime cumulative incidence of acute anterior uveitis (AAU) was determined in a sample of a large population (n = 10,500). Nine hundred seventeen subjects, who answered the question "Have you ever had a red eye" in the affirmative in 1977, were asked to participate in a follow-up study 10 years later. From the 917 respondents, 539 were studied completely. A questionnaire was used to collect historic data, and confirmation of these data was obtained from the treating ophthalmologists and physicians. From these data, subjects were selected for an ophthalmologic examination. The respondents also underwent a rheumatologic examination. The results revealed that the lifetime cumulative incidence of definite AAU is approximately 0.2% in the general population and 1% in the histocompatibility antigen HLA-B27-positive population. In one third of the definite AAU patients, the cause of the disease was known. The lifetime cumulative incidence of definite AAU of unknown cause was 0.15% in the general population. When possible and probable AAU are included, the lifetime cumulative incidence of AAU in the general population is about 0.4%. The observed frequency of the concurrence of AAU and ankylosing spondylitis (AS) was 0.4% in the HLA-B27-positive population and 0.02% in the HLA-B27-negative population. Comparison with the expected frequency of the concurrence of AAU and AS revealed that AAU and AS probably are related diseases irrespective of the association of both diseases with HLA-B27.     

HLA and uveitis

Summary The association between HLA-A29 and birdshot chorioretinopathy is the strongest of all associations between HLA and disease. Determination of HLA-A29 is even of diagnostic significance. The association between HLA-B27 and acute anterior uveitis (AAU) is much weaker, but B27 positive AAU may be considered as a distinct clinical entity. B27 positive patients with AAU should be referred to a rheumatologist, because half of these patients have ankylosing spondylitis or Reiter's syndrome. The determination of HLA-Bw51 is of limited but significant diagnostic value for the diagnosis of Behçet's disease.The present article shows how HLA determinations can serve as diagnostic tests. It is explained how the sensitivity and specificity of such tests can be used to calculate the influence of positive or negative results on the probability of the diagnosis.The structure and function of HLA class I molecules is now known to a great extent. This may lead to a better understanding of the pathogenic role of HLA-A29, HLA-B27, HLA-Bw51 and other HLA molecules which are associated with uveitis.Abbreviations HLA human leucocyte antigen - AAU acute anterior uveitis - RR relative risk     

Clinical features and outcomes of HLA-b27-positive and HLA-B27-negative acute anterior uveitis in a Turkish patient population

PURPOSE: To compare the clinical features and outcomes of HLA-B27-positive and HLA-B27-negative acute anterior uveitis (AAU) in a large Turkish patient population. METHODS: Forty-four patients with HLA-B27-positive AAU and 65 with HLA-B27-negative AAU were reviewed retrospectively. HLA-B27 typing, gender, laterality, clinical features (fibrinous reaction, hypopyon formation), ocular complications, medical treatment, and final visual acuity were recorded. Statistical analyses included Student's t-test, Fisher's exact test, Yate's corrected Chi2 test, and Mann-Whitney U test. A p-value of <0.05 was considered statistically significant. RESULTS: Forty percent of all patients with AAU were found to be positive for HLA-B27 antigen. HLA-B27-positive AAU was significantly more common in males and HLA-B27-negative AAU in females. Unilateral or bilateral alternating AAU as well as fibrinous reaction and hypopyon formation were more common in HLA-B27-positive patients. Posterior iris synechiae and cataract formation were more common and systemic immunosuppressive agents were exclusively required in patients with HLA-B27-negative AAU. Visual outcome did not differ significantly between the HLA-B27-positive and HLA-B27-negative groups. CONCLUSIONS: HLA-B27 association is less common in Turkish patients with AAU than in other populations reported in the literature. Although distinct features of HLA-B27 uveitis were confirmed in our study, visual outcome did not differ from idiopathic AAU. Therefore, we believe that HLA-B27 typing in patients with AAU helps the clinician with the diagnosis. However, it has a limited value in determining the prognosis.     

Acute anterior uveitis and HLA-B27

All studies among acute anterior uveitis patients (AAU) agree on the importance of and high association with HLA-B27. However, the majority of the HLA-B27⁺ population will never develop AAU. The partial association of AAU and HLA-B27 is probably not based on a preferential association with a particular B27 subtype, since the HLA-B27 subtypes are equally distributed among normal controls and AAU patients. Therefore, other factors increase the susceptibility to HLA-B27 associated diseases. Family investigations among the relatives of AAU and AS patients suggest the existence of other pathogenic genetic factors in addition to HLA-B27. Due to extensive research, associations with other genes on chromosome 6 could almost be excluded and associations with genes on other chromosomes were not yet found. The only reproducible association between AAU and any genes or gene products is, at the moment, still the association with HLA-B27. However, its role, which most probably is functional, is far from clear.     

The use of HLA-B27 as a diagnostic and prognostic aid in acute anterior uveitis (AAU) in The Netherlands

Acute anterior uveitis (AAU) may be considered to be one manifestation of the seronegative spondylarthropathies of which ankylosing spondylitis (AS) is the prototype, especially when the patient is HLA-B27 positive. However, it is not yet clear under which circumstances a patient with AAU should be referred to the rheumatologist. In a retrospective study we evaluated the management of 68 consecutive HLA-B27+ AAU patients from a rheumatologic point of view. Although the majority (73%) showed rheumatic problems, only half (52%) of the patients was referred to a rheumatologist, due to problems in evaluation of clinical history and of x-ray reading of the sacroiliac (SI) joints. Because HLA-B27 typing will determine whether the AAU patients "at risk" have AS or a related arthropathy, we suggest using HLA-B27 typing in AAU patients as a diagnostic and prognostic aid. When the AAU patient is found to be HLA-B27 positive, the rheumatologist will be able to "split" these patients into those with AS and those without. Early diagnosis of AS in AAU patients is important as an early start of drug therapy and physiotherapy may prevent deformities and improve final rheumatologic outcome.     

HLA-B27 Anterior Uveitis: Immunology and Immunopathology

Acute anterior uveitis (AAU) is the commonest type of uveitis and HLA-B27 AAU is the most frequently recognized type of acute anterior uveitis and anterior uveitis overall. Recent evidence indicates that acute anterior uveitis is a heterogenous disease, is polygenic and is frequently associated with the spondyloarthropathies (SpA). Studies of patients with AAU and animal models of disease indicate a role for innate immunity, the IL-23 cytokine pathway and exogenous factors, in the pathogenesis of both SpA and acute anterior uveitis. Recently described genetic associations cluster around immunologic pathways, including the IL-17 and IL-23 pathways, antigen processing and presentation, and lymphocyte development and activation. Patients with ankylosing spondylitis (AS) and AAU share other genetic markers, such as ERAP-1, which show strong evidence of gene–gene interaction and point to new mechanisms of disease pathogenesis. These observations have major implications for understanding the pathogenesis of HLA-B27 diseases, such as AAU, and may lead to the development of more specific therapy for AAU.

Received 6 January 2016; revised 6 February 2016; accepted 18 February 2016; published online 31 May 2016