Clinical Features and Prognosis of HLA-B27 Positive and Negative Anterior Uveitis in a Korean Population

Clinical features and prognosis of HLA-B27 positive anterior uveitis (AU) were assessed compared with HLA-B27 negative AU in a Korean population, based on the medical records of AU patients seen at a university hospital. Twenty-seven HLA-B27 negative, idiopathic AU patients (group I) and 55 HLA-B27 positive AU patients (group II) were studied. HLA-B27 positive group was further divided into 29 with associated systemic disease (seronegative spondyloarthropathy) (group IIA) and 26 without associated systemic disease (group IIB). Significantly more severe anterior chamber inflammation in terms of anterior chamber cells (P=0.006) and hypopyon formation (P=0.034) was observed with higher frequency of AU attacks (P=0.007) in the HLA-B27 positive group than in the HLA-B27 negative group. Systemic/periocular steroids were required in significantly more patients in the HLA-B27 positive group than in the HLA-B27 negative group (P=0.015). However, no significant differences were observed for final ocular and visual outcomes between these two groups. Associated systemic disease made no significant difference in the clinical features and prognosis in the HLA-B27 positive AU patients. In conclusion, despite more severe inflammation and a higher recurrence rate, HLA-B27 positive AU shows similar good final ocular and visual outcomes compared to HLA-B27 negative, idiopathic AU in a Korean population.     

Structural homologies between two HLA B27-restricted peptides suggest residues important for interaction with HLA B27

Recently we described an HLA B27-restricted peptide derived from HIV gag p24 protein. In this study we have isolated an HLA B27-restricted peptide from the nucleoprotein (NP) of influenza A virus. The shortest fragment recognized by cytotoxic T lymphocyte (CTL) is eight amino acids long, residues 384-391. Comparison of the sequence of these two HLA B27 restricted peptides reveals homologies which can be aligned from one peptide to the other. Of the eight residues, two are identical: tryptophan and isoleucine. Both peptides have a positively charged residue at the N terminus, lysine at position 265 of gag and arginine at position 384 of NP. Using modified peptides we have shown that lysine or arginine is crucial for the interaction with HLA B27. The wild-type gag peptide blocked CTL recognition of NP peptide by influenza-specific CTL, but removal of the lysine prevented inhibition of NP peptide recognition. The importance of these charged residues was confirmed by the observation that truncated NP and gag peptides where the lysine or arginine was removed were not recognized by specific CTL. Further studies showed that the tryptophan residue influenced the association of the gag peptide with HLA B27, because the affinity of the gag peptide for B27 was strongly increased after replacing this residue with a leucine or a tyrosine. However, these peptides were not recognized by gag-specific CTL, suggesting that the tryptophan may interact with both HLA B27 and T cell receptor. These observations should help in the identification of HLA B27-restricted peptides from other viruses or organisms.     

HLA B27 polymorphism in Western India

We have characterized HLA B27 alleles in a sample population of Maharastra, Western Indians (n = 51), with the aim to investigate the different subtypes present among this population. The study was carried out using polymerase chain reaction with sequence-specific primers (PCR-SSP) and reverse line strip (RLS) techniques. Significant new findings have arisen from this study: B*2704, B*2705, B*2707, B*2708 and B*2714 alleles were found to be present, and two novel B27 alleles, B*2708 and B*2714, were found in this Indian population. In addition, B*2714 was observed in a patient with ankylosing spondylitis. This association has not been previously reported in ethnic groups from India.     

Long-Term Stability of Uveitis with Faint Anterior Chamber Flare Treated with Once-Daily Topical Ophthalmic Betamethasone

The aim of our study is to investigate the long-term transitions of intraocular pressure (IOP) and aqueous flare values in uveitis patients with faint anterior chamber flare who were treated with once-daily topical ophthalmic betamethasone for more than 6 months. The study included a total of 111 eyes of 68 outpatients. The mean follow-up period was 26.8 months. The average IOP and aqueous flare value of patients divided by the 5-months follow-up period showed no significant difference. Six eyes (of four patients) were followed-up for more than 1 year after termination of the treatment. Among these patients, the average aqueous flare value was significantly higher, and the average period to reach more than 1.5 times the former aqueous flare value significantly decreased after termination than before. Once-daily topical ophthalmic betamethasone is not expected to cause steroid-induced ocular hypertension but to have prophylactic effect.     

Identification of HLA B27 antigen by flow cytometry

Cytofluorograph analysis after immunofluorescence with monoclonal antibodies can be useful for various antigens identification on the surface of cell membrane. This technic is described for antigen HLA B27 identification. This HLA antigen is known indeed to be linked to rhumatismal diseases. The fluorescence histograms obtained, allow to differentiate easily subjects which have HLA B27 phenotype and subjects which are HLA cross linked.     

HLA expression and function in single and double HLA-B27-transgenic mice

The expression and function of HLA antigens in mice single transgenic for HLA-B27.2 (sTGM-B27.2) or double transgenic (dTGM) for HLA-B27.2 and human beta 2-microglobulin (h beta 2m) were compared. B27.2 could be well detected on the cell membrane of lymphocytes of sTGM. However, the expression in sTGM was much lower than in dTGM mice. Nevertheless, also in sTGM mice, the B27-transgene product possessed all functional properties of a class I HLA molecule. This was shown by the recognition and induction of antibodies and cytotoxic T cells, by the induction of "allo"-immunity, including skin graft rejection, and by the ability to present viral antigens. In dTGM, the expression of B27 on peripheral blood lymphocytes, spleen and lymphnode cells was comparable to H-2. However, on thymocytes, a relatively lower expression of HLA than H-2 was observed. This low expression of B27 on thymocytes is in concert with the observation that B27 is expressed only in the medulla of the thymus and not detectable in the cortex.     

Role of HLA B27 in diagnosis of seronegative spondyloarthropathies

Seronegative Spondyloarthropathies (SSA) is a very common problem in our area. The main aim of present study was (1) to find the HLA B27 positivity in patients presenting with sacroileitis (2) to see the correlation of B27 positivity on haematological, radiological and extra articular manifestations. Total 110 patients of SSA were studied between July 2004 to June 2005. Routine haematological and immunological test were done by standard method. Total positivity of B27 in SSA was 43.63%, HLA B27 positivity was higher in children (68.75%). Sex wise analysis of B27 positive cases showed that 81.81% B27 positive patients were males. In HLA B27 positive cases lower spine, hip, sacroiliac, shoulder and knee joints were more involved (77.08%, 79.16%, 79.16%, 37.50% and 50.00% respectively). Urinary tract infection (UTI), diarrhoea and constipation were more common in B27 positive cases. Leukocytosis of neutrophilic type (33.33%), raised ESR (77.55%)., CRP positivity (63.63%) and anaemia (65.00%) were seen more frequently in B27 positive cases. In bilateral sacroiliitis diagnosed by X-ray, only 69.23% patient were B27 positive. Our study concludes that HLA B 27 positivity is higher in SSA seen in childhood and in young adult males. B27 positive patients have more severe disease and systemic manifestation Hence, male patients specially young adolescent or young adults with sacroileitis must be subjected for B27 typing.     

High Efficacy of Methotrexate in Patients with Recurrent Idiopathic Acute Anterior Uveitis: a Prospective Study

Archivum Immunologiae et Therapiae Experimentalis - To evaluate prospectively the efficacy of methotrexate (MTX) in the treatment of recurrent idiopathic acute anterior uveitis (RIAAU). Nineteen...     

HLA B-27 subtypes in Turkish patients with spondyloarthropathy and healthy controls

The frequency and the distribution of HLA-B27 subtypes in spondylarthropathy (SpA) patients and controls were investigated in a sample Turkish population. B27 subtyping was performed by PCR-SSP method in two groups: 49 unrelated HLA-B27 positive Turkish patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group Criteria, and 55 HLA-B27 positive healthy controls. The frequency of HLA-B*27 was 2.6% in the Turkish population, and B*2705 was the predominant allele among patients with SpA. The difference was mainly between male patients and male controls The proportion of B*2705 among B27-positive patients and controls was significantly different (P=0.02). Our study supports other reports from different populations which showed that B*2705 and B*2702 were more frequent in Caucasian patients with SpA.     

强直性脊椎炎病人HLA B27等位基因与HLA A、B 抗原关系分析

目的　调查强直性脊椎炎（ Ａ Ｓ） 病人中 Ｂ２７ 等位基因与其它 Ｈ Ｌ Ａ Ａ、 Ｂ 抗原之间的关系,为 Ａ Ｓ 与 Ｂ２７ 关联机理提供线索。方法　 Ｈ Ｌ Ａ Ａ、 Ｂ 抗原分型采用 Ｎ Ｉ Ｈ 标准微量淋巴细胞毒方法, Ｂ２７ 等位基因的检测采用聚合酶链反应／ 顺序特异的寡核苷酸探针方法。对上海地区６８ 例 Ａ Ｓ 病人和３１８ 例正常对照进行调查。结果　 Ａ Ｓ 病人根据其所检定的 Ｂ２７ 等位基因主要可分为 Ｂ２７０４和 Ｂ２７０５ 二大组, Ｈ Ｌ Ａ Ａ１１ 的频率在 Ｂ２７０４ Ａ Ｓ 组要比正常对照组显著增高（ Ｐ＝ ００００ ９８ , Ｐｃ＜ ０ ．０１） ,在 Ｂ２７０５ Ａ Ｓ 组则比正常对照组稍低（ Ｐ＞ ０ ．０５） , Ｂ２７０４ 与 Ｂ２７０５ Ａ Ｓ 组之间差异也有统计学意义（ Ｐ＜ ０ ．０５） 。结论　上海地区携带 Ｂ２７０４ 的 Ａ Ｓ病人与 Ｈ Ｌ Ａ Ａ１１ 抗原相关,提示 Ｂ２７０４ 与 Ｂ２７０５ 在 Ａ Ｓ 发病中的具体作用可能有所差异,或 Ｂ２７０４ 与 Ａ１１ 之间存在连锁不平衡。     

HLA class II and HLA-B27 oligotyping in two Siberian native population groups

Abstract: It was the purpose of this study to better define the frequency of HLA-B27 subtypes and HLA class II alleles among indigenous populations from the eastern tip of the Chukotka Peninsula of Siberia, Russia, which have higher frequencies of HLA-B27 (40%) and spondyloarthropathies (2%) than Caucasian populations and test the hypothesis that these populations are more closely related to Orientals. Siberian Eskimos and Chukchi residing in four coastal villages on the Chukotka Peninsula inhabited by Siberian Eskimos and Chukchi people were examined using oligotyping of the polymerase-chain reaction-amplified second and third exons of the HLA-B27 gene. HLA-class II alleles (DRB1, DQA1 and DQB1) were similarly determined. Of 88 HLA-B27 positive individuals from these villages, all had HLA-B*2705, including the four patients with Reiter's syndrome and the five ankylosing spondylitis, except one Eskimo control who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. HLA-class II typing in 70 Siberian Eskimos and 71 Siberian coastal Chukchi revealed HLA-DRB1*0401, DRB1*0802, *0901 and *1402 to account for nearly all the DRB1 alleles found in this population, similar to what has been described in Eskimos in Alaska, but different from Chinese or native Americans in the U.S. The overwhelming majority of the individuals examined had HLA-DQB1*0301, similar to what has been observed in Native Americans. The Siberian Eskimos differed from the coastal Chukchi only in the occurrence of HLA-DRB1*0701, DQA1*0201, DQB1*0201 alleles, which occurred only in the former group. These data suggest that the Chukotka population is genetically more closely related to Caucasians and native Americans and less to other Oriental populations.     

pANCA Antibodies in Patients with Anterior Uveitis: Identification of a Marker Antibody Usually Associated with Ulcerative Colitis

A pANCA autoantibody (antineutrophil cytoplasmic antibody, perinuclear pattern) has been described in uveitis patients, but its correlation with systemic illnesses and the specific type of pANCA has not been defined. The goals of this study were to determine the (1) frequency of pANCA autoantibodies in uveitis, (2) systemic associations in the pANCA+ uveitis patients, and (3) type of pANCA antigen recognized by the uveitis-associated autoantibody. Serum was obtained from 59 patients with anterior uveitis or panuveitis and from nonuveitis controls. A detailed medical and family history was obtained from each subject at the time of phlebotomy. Sera were screened by neutrophil ELISA to determine the frequency of ANCA positivity. Immunofluorescence assays were then used to differentiate cANCA from pANCA. The specificity of the pANCA+ antibodies was further characterized by DNase 1 sensitivity and granule antigen ELISAs. ANCA antibodies were detected in 29% of all patients with panuveitis or anterior uveitis. In 41% of these ANCA+ patients, serum antibody detected a perinuclear antigen that was sensitive in all cases to DNase 1. The majority of pANCA+ uveitis patients were either HLA-B27 positive or had systemic evidence of immune-mediated diseases. Two pANCA+ patients had no medical or family history of other immune-mediated diseases. This study identifies a subset of uveitis patients distinguished by expression of a specific pANCA marker antibody, The characteristics of this antibody are similar to the pANCA antibody present in most patients with ulcerative colitis. Expression of the pANCA autoantibody in uveitis patients is a susceptibility marker for other immune-mediated diseases.     

Complete heart block — another HLA B27 associated disease manifestation

An increased prevalence of ankylosing spondylitis and other HLA B27-associated rheumatic diseases has recently been demonstrated in a group of men with permanent pacemaker-treatment. The purpose of the present study was to find out if HLA B27 was associated with severe bradyarrhythmias also in the absence of rheumatic disease.
The frequency of B27 was determined in 83 permanently paced men with complete heart block, in whom presence of radiological or clinical signs of a B27-associated rheumatic disease had been excluded. Eighty-four healthy subjects were HLA typed for comparison.
HLA B27 was found in 17% of the patients and in 6% of the controls, a significant difference with P = 0.017 (Fisher's exact test). The present study suggests that, in a subgroup of patients with complete heart block, the development of heart block is B27-associated, and that the pathophysiological mechanism is similar to that leading to ankylosing spondylitis.
Another B27-associated disease manifestation has been demonstrated.     

HLA B27 as Predisposition Factor to Suffer Age Related Macular Degeneration

To research whether specific alleles HLA class Ⅰ （HLA-A and HLA-B） and class Ⅱ （HLA-DR） are risk factors for the development of exudative type of Age Related Macular Degeneration（ARMD）, HLA antigens are expressed both in normal and affected eyes with ARMD. We designed a prospective case-controlled study. We recruited 75 patients with choroidal neovascuiarization predominantly classic or occult, secondary to ARMD, and treated with photodynamic therapy. Two hundred and fifty patients over 55 years old, without ophthalmologic pathology who went to hospital for an analytical routine check were used as control. The analysis of the data shows a significant difference between two groups. Allele HLA-B27 correlated positively with ARMD （p 〈 0.0113）. However, we didn＇t find alleles negatively associated. Thus HLA-B27 is an allele predisposed to suffer ARMD.     

Molecular mimickry between HLA B27 and Yersinia, Salmonella, Shigella and Klebsiella within the same region of HLA alpha 1-helix.

Two new examples of amino acid homology between HLA B27 and microbes triggering HLA B27-associated diseases are described. An outer membrane protein YadA (Yersinia adhesin, previously called Yop1) of Yersinia enterocolitica and Y. pseudotuberculosis shares a linear tetrapeptide with HLA B27. A cationic outer membrane protein OmpH of Salmonella typhimurium shares homology with five amino acids of HLA B27 in a non-linear fashion. The four amino acids of YadA are also notably included in the hexapeptide identical between Klebsiella pneumoniae nitrogenase and HLA B27, and three of them occur in the pentapeptide shared by a Shigella flexneri protein and HLA B27. Antibodies against synthetic peptides including HLA B27 homologues sequences of YadA and OmpH were observed in one-third of the patients with HLA B27 associated diseases. Antibodies were directed against a flanking sequence next to the amino acid sequences shared by arthritis-triggering microbes and HLA B27. The area of identity in each example of this molecular mimicry (Yersinia, Salmonella, Shigella and Klebsiella) is located in the same place on the HLA B27 molecule: between amino acids 70 to 78 in the variable region of alpha 1-helix. This area of HLA B27 molecule includes sites predicted to be important for binding processed antigens.     

Uveitis in Mouse and Man

Uveitis is underappreciated as a sight-threatening cause of blindness. There are two broad causative classes of uveitis: infectious and non-infectious. Non-infectious uveitis is considered a prototypical autoimmune disorder based mainly on data from experimental models in the mouse. Several different experimental models exist that reflect the different types of uveitis in man (anterior, intermediate, and posterior uveitis). These models have demonstrated that uveitis is predominantly a Th1/Th17 mediated disease, although innate immune cells play a significant role both in induction of disease and in tissue damage. Most experimental models of uveitis rely on activation of the innate immune system by use of adjuvants that activate a range of pathogen recognition receptors (PRRs). This begs the question of the underlying role of initial and/or persistent infection, including latent infection, in immune-mediated uveitis in which active infection cannot be demonstrated. This further raises the possibility of pathogenic mechanisms such as antigenic cross-reactivity and molecular mimicry. Alternatively, residual/latent antigen from infectious agents may act as “endogenous” adjuvants for induction of immune reactions to damaged/altered self antigen, suggesting a commonality in pathogenesis for both infectious and non-infectious uveitis in man.