Non-granulomatous anterior uveitis and HLA-B27 antigen

In Caucasians, there is close correlation between acute anterior uveitis and histocompatibility antigen HLA-B27. But in Japanese, this is not clear. Therefore, we examined 58 patients with non-granulomatous anterior uveitis (NGAU) about HLA typing in our uveitis clinic at Tokyo Women's Medical College Hospital. HLA-B27 was identified in 20 out of 58 patients (34.5%) with NGAU and it was statistically significant. We also studied the clinical features of patients with HLA-B27 positive NGAU. We found that in HLA-B27-positive NGAU, the visual acuity was more strongly affected during the attack and the duration of inflammation was longer than HLA-B27 negative NGAU patients. The duration of the first attack was longer than re-attack, and the duration of the first attack was longer than HLA-B27 negative NGAU patients. It was less commonly associated with systemic disorders in Japanese HLA-B27 positive anterior uveitis than in Caucasian. However, in Japanese NGAU patients without systemic disorders, there was the same tendency concerning the HLA-B27 positive rate as in Caucasians.     

Acute anterior uveitis, ankylosing spondylitis, back pain, and HLA-B27.

One hundred and sixty-nine patients with acute anterior uveitis were studied for the presence of HLA-B27 tissue type, radiological evidence of ankylosing spondylitis, and a history of back pain. 60% were male; 45% were HLA-B27+. The male:female ratio in the HLA-B27+ group was the same as in the whole group. 24% had radiological evidence of ankylosing spondylitis, and, of these, 83% were HLA-B27+ while 17% were HLA-B27-. There was a definite correlation between the severity of the ankylosing spondylitis and preponderance of males in the HLA-B27+ group of patients. Significant back pain occurred in 60% of HLA-B27+ patients but in only 14% of HLA-B27- patients. The importance of the selection of patients and of consistency in the use of diagnostic criteria in studies relating to ankylosing spondylitis and acute anterior uveitis is stressed.     

HLA-B27, Klebsiella pneumoniae, and the relation to acute anterior uveitis

Acute anterior uveitis (AAU) is a disease of unknown etiology, although it is frequently associated with various autoimmune diseases. It has recently been shown in patients with ankylosing spondylitis (AS), a disease often associated with AAU, that antiserum raised against a particular isolate of Klebsiella pneumoniae would cross-react with lymphocytes possessing HLA-B27. The present study was performed to evaluate the response of lymphocytes of patients to K. pneumoniae and to determine the correlation with HLA-B27. The circulating immune complex levels in the serum of the patients were also determined for correlation with the presence of HLA-B27 antigen. We were able to demonstrate this cross-reactivity in the samples of AAU patients; however, we did find an increased immune complex level that was independent of HLA-B27 antigen. From our results, we conclude that although AAU is clinically associated with AS, the role of K. pneumoniae in these disease states remains unclear.     

HLA-B27+ acute anterior uveitis and other antigens of the major histocompatibility complex

Acute anterior uveitis (AAU) is associated with HLA-B27 in 50% of the patients. Although the association between HLA-B27 and AAU is evident, other genetic factors probably also play a pathogenic role. To investigate whether HLA-B27 only serves as a marker gene for genes next to the B-locus, class I and II HLA antigens of 62 HLA-B27+ AAU patients were determined. Increased frequencies were found for HLA-Cw1, Cw2, DR4, DRw12 and DQw3 if the AAU patients were compared with normal controls. However, when the data were compared to a group of HLA-B27+ controls, no differences were observed. The supposed associations were therefore probably due to linkage disequilibrium with HLA-B27. Homozygosity for HLA-B27 seemed not to increase the chance to acquire AAU. HLA-DR4 was present less frequently in AAU patients with ankylosing spondylitis than in AAU patients without this disease. Haplotype analysis of 21 families revealed that not all relatives suffering from AAU shared the HLA-B27+ haplotype with the proband. Of seven relatives suffering from AAU, five carried the same HLA-B27+ haplotype as the proband, one had inherited another HLA-B27+ haplotype and the last one was HLA-B27-. In conclusion, we could not bring forward any reason to suggest that genes on the short arm of chromosome 6--other than HLA-B27--play a role in the pathogenesis of HLA-B27+ AAU.     

Efficacy of golimumab on recurrent uveitis in HLA-B27-positive ankylosing spondylitis

To evaluate the efficacy of golimumab on severe and frequent recurrent anterior uveitis in patients with HLA-B27-positive ankylosing spondylitis. In this study, 15 eyes of 12 HLA-B27-positive AS patients with resistant anterior uveitis who received 50 mg of subcutaneous golimumab (Gol) per month due to frequent uveitis recurrences were analyzed retrospectively between May 2013 and October 2015. Assessment criteria were uveitis activity, the number of recurrence of uveitis, visual acuity, systemic corticosteroid, or other drug requirement for maintenance of remission of AU. Twelve patients (15 eyes) with HLA-B27-positive ankylosing spondylitis and anterior uveitis have been treated with golimumab 50 mg/month. Remission of uveitis was observed in 12 eyes out of 15. Malign hypertension developed in one subject after the second dose of golimumab therefore the treatment was stopped and this subject was excluded from the study. Median follow-up time was 11 months (interquartile range: 8–18). No uveitic reaction was seen except in the patient who stopped treatment. No topical or systemic steroid necessity was needed except in two cases with oral 4 mg systemic maintenance. Visual acuity was significantly increased (p = 0.002). Golimumab may be a new and effective choice for maintaining remission and the prevention of recurrences of severe, resistant anterior uveitis in patients with HLA-B27-positive ankylosing spondylitis.     

Anterior uveitis in ankylosing spondylitis: a histocompatibility study

The occurrence of acute anterior uveitis in ankylosing spondylitis was compared in 53 HLA-B 27 positive and 12 HLA-B 27 negative patients with this disease. Uveitis was found in HLA-B 27 positive patients only. These results suggest that uveitis and ankylosing spondylitis are independent diseases occurring on their own and strongly associated with HLA-B 27.     

HLA-B27 frequency and MLC reactions in acute anterior uveitis

HLA-A and B antigens were determined in 37 unrelated patients with acute non-granulomatous anterior uveitis (AAU) and in 114 control subjects. HLA-B27 was identified in 31 patients with AAU (83.8%) and in 15 control subjects (13.2%). Fifteen patients (40.5%) had associated rheumatic diseases and all of them (100%) had HLA-B27. Of the 22 patients without any associated disease, 16 (72.7%) had HLA-B27. To study the HLA-D composition MLC tests were done as one-way microcultures between members of four groups consisting of 10, 10, 8, and 8 patients with AAU and two or three healthy controls in each test group. No difference between patient-to-patient reactions as compared with the control reactions could be observed. The results show that AAU is very closely associated with HLA-B27 but not with any of the HLA-D antigens.Supported by grants from The Finnish Rheumatism Association, The Medical Research Council of the Academy of Finland, and The Sigrid Jusélius Foundation, Finland     

HLA-B27抗原与前葡萄膜炎的相关性及其临床意义

探讨ＨＬＡ－Ｂ２７抗原与前葡萄膜炎的相关性及可能的意义。方法用多聚酶链反应（ＰＣＲ）和微量淋巴细胞毒试验对２０例伴有关节强直性脊椎炎（ＡＳ）的急性前葡萄膜炎（ＡＡＵ）、６７例ＡＡＵ、７０例慢性前葡萄膜炎和７０８个健康人进行ＨＬＡ－Ｂ２７分型。结果ＡＳ伴有ＡＡＵ和单纯的ＡＡＵ患者ＨＬＡ－Ｂ２７阳性率分别为７０％和４９．２５％,显著高于对照组（２．９７％,Ｐ〈０．００１）,慢性前葡萄膜炎患者中ＨＬＡ－     

合并成型性渗出的急性前葡萄膜炎与HLA-B27的相关性研究

目的 探讨急性渗出性前葡萄膜炎与HLA-B27的相关性。方法 对53例前房内出现成型性渗出的急性前葡萄膜炎（AAUPE）患者及61例前房内无成型性渗出的急性前葡萄膜炎（AAU）患者进行HLA-B27的检测,并结合临床表现加以分析。结果 成型性渗出的AAUPE患者的HLA-B27阳性率为100％,而无成型性渗出的AAU患者的HLA-B27阳性率仅为50.8％。二者有显著差异性（P<0.01）。两组HLA-B27阳性的病人强直性脊柱炎发生率分别为50.0％和42.9％。结论 结果进一步证实了HLA-B27与成型性渗出密切相关的论点。提示检测AAU患者HLA-B27的阳性率,发现成型性渗出裂隙灯检查似与血清法检测同样准确。     

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.     

HLA-B27阳性急性前葡萄膜炎的临床特征

目的 :探讨HLA B2 7阳性急性前葡萄膜炎的诊断及临床特征。方法 :应用磁珠酶联免疫吸附试验对 74例急性前葡萄膜炎患者和 36例健康对照者血液中HLA B2 7抗原进行测定 ,并对HLA B2 7抗原阳性和阴性急性前葡萄膜炎患者的临床特征进行对比分析。结果 :急性前葡萄膜炎患者 74例中 ,HLA B2 7抗原阳性 35例 ,阳性率为 4 7 30 % ;健康对照者 36例 ,阳性 3例 ,阳性率为 8 33% ;两者有显著性差异 (χ2 =16 2 6 ,P <0 0 1)。HLA B2 7阳性急性前葡萄膜炎的临床特点有起病急、前房内有大量纤维渗出和细胞、角膜后沉着物呈细小、灰白色。一般为单眼发病 ,症状重于常见的特发性前葡萄膜炎 ,复发率较高。常伴有玻璃体混浊、黄斑囊样水肿和全身关节病变。结论 :HLA B2 7抗原与急性前葡萄膜炎明显相关 ,HLA B2 7相关性前葡萄膜炎的临床表现重于HLA B2 7阴性前葡萄膜炎 ,并常伴有全身脊柱关节病变。     

HLA-B27 frequency in Greek patients with acute anterior uveitis.

The histocompatibility antigen HLA-B27 was identified in 12 out of 33 patients with acute non-granulomatous anterior uveitis. This is a frequency of 36.36%, compared with 4.72% in controls. Seven patients had in addition evidence of systemic disease, including ankylosing spondylitis, sacroiliitis, Reiter's disease, Still's disease, and rheumatoid arthritis. Five of these were HLA-B27 positive, which suggests that the uveitis in many of these cases has a similar aetiology to the uveitis in those with rheumatic disease. It appears that the more severe cases of acute anterior uveitis are related more frequently to the presence of HLA-B27.     

Inheritance of acute anterior uveitis and HL-A antigen 27

Summary A family study on the inheritance of HL-A antigens and susceptibility to acute anterior uveitis is reported. In the 4 families examined, the antigen 27 (haplotype 2.27) occurred in all of the 7 patients with acute anterior uveitis and in 22 of the 33 healthy family members examined. It is suggested that in Finns the haplotype 2,27 is linked with genes predisposing the carrier to acute anterior uveitis.

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Zusammenfassung Familienuntersuchung über die Erblichkeit des HL-A-Antigens im Zusammenhang mit Erkrankung an akuter Uveitis anterior. In 4 untersuchten Familien wurde das Antigen 27 (Haplotyp 2,27) bei allen 7 Patienten mit akuter Uveitis anterior nachgewiesen, ferner bei 22 von 33 gesunden untersuchten Familienmitgliedern. Es wird angenommen, daß bei Finnen der Haplotyp 2,27 mit Genen gekoppelt ist, welche den Träger zu einer Erkrankung an akuter Uveitis anterior disponieren.

     

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。     

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.     

An HLA-B27 negative case of ankylosing spondylitis with acute iridocyclitis]

The author experienced a 34-year-old male case of acute iridocyclitis with fibrinous exudates accompanied by ankylosing spondylitis with negative HLA-B27. Who was diagnosed definite ankylosing spondylitis by the New York criteria. The cause of ankylosing spondylitis was postulated to be a cross reaction between HLA-B27 and a certain Gram-negative bacillus. However, our case with negative HLA-B27 suggested the causes could comprise multiple factors in addition to HLA-B27. Since the clinical picture of iridocyclitis observed in our case showed no difference with those of HLA-B27 positive cases, iridocyclitis associated with ankylosing spondylitis is considered to be the same entity regardless of HLA-B27 being present or not.     

Clinical features of ankylosing spondylitis associated with acute anterior uveitis in Chinese patients

AIM: To characterize the clinical features, diagnosis, treatment and prognosis of uveitis associated with ankylosing spondylitis (AS) in Chinese patients. METHODS: Two hundred and three patients with uveitis associated with AS followed-up in the Third Military Medical University Daping Hospital between 2005 and 2010 were retrospectively evaluated in this study. Complete ophthalmological examinations were evaluated at baseline and during the follow-up period. The gender, age, follow-up time, mean frequency of uveitis onset, and accompanying eye examination findings, history, demographical parameters were reviewed. All the patients presented complete clinical and radiologic (sacroiliac, lumbar, dorsal and cervical spine, knee, ankle, shoulder, hip, elbow) evaluation. HLA-B27 typing was also searched. RESULTS: There were 203 patients diagnosed with AS associated uveitis. All showed sacroiliac X-ray changes indicative of AS. There were 184 male and 19 female patients. The average age of patients was 35±12 (range 18–50). Mean follow-up period was 2.4 years (1-5 years). Acute anterior uveitis was the most common type of uveitis in both genders. 121 eyes presented unilateral involvement (55.2%), and 92 eyes presented bilateral involvement (45.3%) with onset alternately. 22 eyes occurred hypopyon, 16 eyes were found anterior vitreous cells, 7 eyes were noted reactive macular edema or exudation, 29 eyes presented posterior synechiae of iris, and 14 eyes presented cataract, 9 eyes presented secondary glaucoma, 2 eyes presented bend corneal degeneration and 1 eyes presented atrophy of eyeball. At the final visit, uveitis was well controlled in most patients. CONCLUSION: AS associated with uveitis in Chinese patients mainly manifests as acute anterior uveitis. A combination of corticosteroids with other mydriasis agents is effective for most AS associated with uveitis patients. In general, the prognosis is good in these cases.     

Seasonal variation of acute anterior uveitis: differences between HLA-B27 positive and HLA-B27 negative disease.

One hundred and seventy-five consecutive patients with acute anterior uveitis (AAU) were examined over a 24-month period. There was a significantly increased incidence of AAU during the months August to December (p less than 0.05). This increase was confined predominantly to the HLA-B27 negative group of patients (p less than 0.01). There was no significant monthly difference in incidence between males and females, between patients with first or recurrent attacks, or between patients with and without arthritis. These results suggest that seasonal environmental factors may play a role in the production of HLA-B27 negative AAU.