Comparison of clinical features in HLA-B27 positive and negative patients with ankylosing spondylitis

The clinical features of ankylosing spondylitis (AS) were compared in 63 HLA-B 27 positive (+) and 15 B27 negative (-) individuals with this disease. There were no differences in age at onset, functional class, degree of deformity, pain, severity of X-ray changes, or frequency of peripheral joint involvement or of reconstructive orthopedic surgery. These data demonstrated that skeletal manifestations of AS were essentially the same in B27(+) and (-) patients, and provide no evidence for the speculation that AS in B27(-) patients is milder or is a different disease from that occurring in B27(+) patients. On the other hand, acute anterior uveitis was found to be significantly more common in B27(+) patients, a fact suggesting that the "uveitis of AS" may in fact be an independent condition occurring in B27(+) individuals, rather than a manifestation of AS per se.     

强直性脊柱炎延误诊断的初步调查和原因分析

目的 调查强直性脊柱炎(AS)延误诊断的情况和分析原因.方法 收集我院门诊或病房就诊的符合1984年修订纽约AS诊断标准的的308例AS患者,通过面对面和电话联系相结合方法,选择13个问题来搜集AS延误诊治的情况;并从误诊时的症状和检查等方面分析延误诊治的原因.结果 238/308例作出了全部问题的回应,其中,男女比例是6:1;①发病年龄:发病年龄<15岁占18.1%,15～39 岁占79.0%,≥40岁占2.9%,平均发病年龄是22.1岁.②男女患者平均确诊年龄分别是(28±8)岁和(31±10)岁;男女患者平均延迟诊断时间差异无统计学意义(P=0.135)③有AS家族患病史的有57例(占23.9%),有家族史的平均延迟诊断时间分别是73.2个月,无家族史的患者平均延迟诊断时间是71.9个月,两组比较差异无统计学意义(P=0.899).④人类白细胞抗原(HLA)-B27(+)占84.9%,HLA-B27(+)组和(-)组平均延迟诊断时间分别是70.1个月和88.1个月,两组比较差异均无统计学意义(p>0.05.但在延迟诊断>10年确诊的AS患者中,24例HLA-B27(+)和10例HLA-B27(-),两组比较差异有统计学义(P=0.012).⑤在238例患者中,误诊率为66.4%,平均延迟诊断时间是(72±68)个月.其中,单次误诊占45.0%,多次误诊的占21.4%,其中有7例延迟诊断≥10年却无出现误诊.最常误诊的疾病包括:与风湿热相关的关节炎(23.4%)、腰肌劳损(22.9%)和椎间盘突出(20.3%)等.结论 AS延误诊治可能与是否HLA-B27阳性和缺乏骶髂关节的X线资料密切相关.     

Clinical patterns and characteristics of ankylosing spondylitis in China

The study aimed to determine whether unique clinical patterns of AS may exist in China, specifically to explore the different clinical manifestations caused by gender, HLA-B27 status, and age at disease onset. The multicenter cross-sectional survey was conducted and 1251 patients were enrolled across China, representing a broad spectrum of Chinese AS patients. The mean age at onset and diagnosis were 29.2 (11.4) and 33.5 (12.6) years, respectively. The male/female ratio was 2.7:1. Acute anterior uveitis (AAU) was experienced in 10.3% of AS patients and 9.1% patients had juvenile-onset AS (JoAS). Men were significantly younger at onset and diagnosis and showed a higher frequency of HLA-B27 positivity, JoAS, and AAU than women. HLA-B27-positive patients had a younger age of onset than HLA-B27-negative patients. HLA-B27-positive patients were nearly three times as likely to develop AAU than negative patients (P = 0.04). JoAS patients had a family history of AS more often than adult-onset AS (AoAS) patients, and 4.9% of JoAS patients underwent surgical treatments, a rate more than six times that of AoAS patients (P = 0.01). Men had higher levels of C-reactive protein than women, as did HLA-B27 positives compared to negative patients, and JoAS compared to AoAS (all P < 0.05). The clinical patterns of our AS patients were similar to those in other studies in non-Chinese cohort: (1) the age at onset was 29.2 (11.4) years, which was older than found in other studies; (2) men were more likely be HLA-B27 carriers than women; and (3) AAU was less common in Chinese patients.     

Characterization and outcome of uveitis in 350 patients with spondyloarthropathies

This retrospective study analyzed 350 patients with the diagnosis of spondyloarthropathies (SPA) (207 with ankylosing spondylitis (AS), 80 with undifferentiated spondyloarthropathies (USPA) and 63 with psoriatic arthritis (PsA)) attended at a tertiary referral hospital for a minimum period of 5 years. All the patients presented complete clinical (axial and peripheral involvement, heel enthesopathies, extra-articular manifestations) and radiologic (sacroiliac, lumbar, dorsal and cervical spine) evaluation. HLA-B27 and respective alleles were searched. These data were compared with the occurrence of uveitis during the follow-up of the SPA patients. Thirty AS patients (14.5%) presented 55 episodes of acute anterior uveitis; there was statistical association between uveitis and juvenile-onset AS (P = 0.0094) and achillean (P = 0.0003) and plantar (P = 0.0067) enthesopathies; one AS patient presented a single episode of posterior uveitis, associated to tuberculosis. Seven USPA patients (8.8%) presented 13 episodes of acute anterior uveitis; it was not observed statistical association with any variable; one patient presented a single episode of posterior uveitis, associated to toxoplasmosis. Five HLA-B27 positive PsA patients (8%) presented 13 episodes of acute anterior uveitis. All the 26 positive HLA-B27 SPA patients with anterior uveitis tested for the HLA-B27 alleles were HLA-B*2705. No patient presented ophthalmologic severe sequelae of the anterior uveitis. Concluding, anterior uveitis was associated to the juvenile onset of the disease and to the enthesophatic involvement of the lower limbs in AS patients. The HLA-B*2705 allele was predominant in the anterior uveitis patients, whilst posterior uveitis was rare and associated to infectious disease.     

Incidence and prevalence of ankylosing spondylitis in Northern Norway

OBJECTIVE: To determine the incidence and prevalence of ankylosing spondylitis (AS) over a prolonged period in the 2 northernmost counties of Norway, where HLA-B27 has a high prevalence in the population. METHODS: We conducted a cohort study of all patients registered with a diagnosis of AS between 1960 and 1993 at the University Hospital of Northern Norway, which is the sole rheumatology department serving these counties. We registered demographics, year of disease onset (clinical disease), and year of diagnosis (radiograph confirmation) for all patients. The date of onset of clinical disease in patients with AS was used in the calculation of incidence rates. Annual incidence and point/period prevalence rates were expressed per 100,000 adults. Primary AS was defined as AS in the absence of psoriasis or inflammatory bowel disease (IBD). RESULTS: A total of 534 patients (75.1% male, mean age at clinical diagnosis 24.2 years, 93.0% HLA-B27 positive) had a confirmed diagnosis of AS (by the modified New York criteria). Median time from disease onset to radiologic confirmation was 8.0 years. Annual incidence of primary AS (n = 417) was 7.26, while estimated point prevalence rose from 0.036% in 1970 to 0.10% in 1980 and to 0.21% in 1990 with a period prevalence of 0.26%. AS was secondary to psoriasis or IBD in 117 patients (18.1%), with a diagnostic delay similar to that in primary AS. Annual incidence (14.1) and period prevalence in 1982-1993 (0.41%) were significantly higher in the town of Troms? than in the surrounding rural region (5.21 and 0.22%, respectively). Mortality in patients with AS was low. CONCLUSION: The incidence of AS was relatively stable in the northern part of Norway over a 34-year period. Incidence and prevalence are higher than reported in similar studies from Finland and Minnesota, possibly due to a higher population prevalence of HLA-B27.     

Ankylosing spondylitis in North India: a clinical and immunogenetic study.

Fifty-one North Indian patients with ankylosing spondylitis (AS) are described with mean age of onset 21.2 years and male to female ratio of 16:1. AS began with peripheral arthritis in 47%, low back pain in 41%, acute anterior uveitis in 10%, and heel pain in 2% of the patients. 76% of 51 patients had one of the extra-axial features of AS: peripheral arthritis (61%), heel pain (24%), anterior uveitis (22%), urethritis (12%), kidney disease (10%), mucosal ulcerations (6%), aortic incompetence (4%), and apical pulmonary fibrosis (4%). A majority (71%) of the patients with peripheral arthritis had mono- or oligoarthritis affecting mainly the lower limb joints. Two patients had coexistent rheumatoid arthritis also. HLA-B27 antigen was detected in 48 (94%) of 51 patients compared with 7 (6%) of 118 controls (relative risk 254; Fisher's exact p = 3.49(-29]. On comparing patients with juvenile onset AS and patients with adult onset disease we found peripheral arthritis to be more frequent at the beginning and during the course of disease in the former.     

TNF-238A promoter polymorphism contributes to susceptibility to ankylosing spondylitis in HLA-B27 negative patients.

OBJECTIVE: To investigate the relative contribution of MHC loci in their susceptibility to primary ankylosing spondylitis (AS) in HLA-B27 negative patients and to compare the clinical features and genetic factors with those of HLA-B27 positive AS. METHODS: DNA from patients with B27 negative primary AS (n = 28), B27 positive primary AS (n = 77), and matched healthy controls (B27-, n = 100; B27+, n = 70) were analyzed to investigate whether HLA genes determine the disease susceptibility, or whether other closely linked loci might play a role in disease development. HLA typing was carried out by serology and PCR/SSP (HLA-B, -DR), MICA-TM polymorphism in the transmembrane region by radioactive PCR, and tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism at positions -238 and -308 by PCR-RFLP. RESULTS: Subtle clinical differences were found for primary AS, the B27 negative patients being less frequently complicated by acute anterior uveitis and more associated with peripheral arthritis than B27 positive. Differences were found in the distribution of TNF-alpha -238 genotypes among patients with primary AS (B27- vs B27+). The TNF-alpha -238(A) polymorphism was present in 50% of the B27 negative patients carrying the -238 G/A and A/A genotypes and was significantly increased compared with B27 positive AS (odds ratio 4.3) and with the B27 negative control group (OR 5.9). The TNF-alpha genotypes were equally prevalent in B27 positive AS and healthy matched B27 positive controls. No significant HLA and MICA typing differences were found between the populations under study. CONCLUSION: Our results indicate that the polymorphism variation in the TNF-alpha promoter -238.2(A) influences disease susceptibility in B27 negative primary AS but had no effect in our B27 positive AS population.     

Quantitative analysis of HLA-B27 by flow cytometry using CD3 gating in seronegative spondylarthropathies.

OBJECTIVE: To investigate the relationship in patients with spondylarthropathies (SpA) between the clinical features of the disease and quantitative flow cytometric expression of HLA-B27 by CD3 gating. METHODS: We performed quantitative analysis of HLA-B27 antigen by flow cytometry using CD3 gating in 61 patients with seronegative and HLA-B27 positive SpA. The patients included 29 with ankylosing spondy-litis (AS), 29 with undifferentiated spondylarthropathy (uSpA), and 3 with reactive arthritis (ReA). In addition, we compared the fluorescence intensity of HLA-B27 with the clinical characteristics of the patients. RESULTS: The fluorescence intensity of HLA-B27 was significantly higher in patients with AS than in patients with other SpAs (220.5 +/- 13.7% vs 182.8 +/- 11.7%, p = 0.04). However, there were no demonstrable correlations between the quantitative expression of B27 and clinical features such as age, disease duration, results of the Schober test, chest expansion, the WBC count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). There was also no difference in the quantitative expression of HLA-B27 based on the presence or absence of uveitis, peripheral arthritis or enthesopathy. However, multiple regression analysis showed that age, disease duration and CRP were independent factors influencing the quantitative expression of HLA-B27 in SpA (beta = 0.568, 0.546, -0.437 and p = 0.006, 0.02, 0.04, respectively). CONCLUSIONS: Our data suggest that the quantitative expression of HLA-B27 may be related to some of the clinical features in patients with SpA.     

Pattern of ankylosing spondylitis in an Iranian population of 98 patients

The prevalence and pattern of ankylosing spondylitis (AS) can vary from country to country, according to genetic and environmental factors. This study aims to analyze the patterns of disease in a population of Iranian patients with AS. We performed a prospective study (2002–2007) analyzing 98 patients with diagnosis of AS according to the modified New York criteria. Selected patients underwent complete clinical (initial symptom, axial and peripheral involvement, heel enthesitis, extra-articular manifestations) and radiological (sacroiliac, lumbar, thoracic, and cervical spine) investigations, and these data were compared with sex, age at onset, and HLA-B27. There was predominance of men (71.4%), adult onset (>16 years, 90.8%), and positive HLA-B27 (73.4%). Family history of AS was noted in 14.3% of the patients. The predominant initial symptoms were inflammatory low back pain (44.2%). Radiological findings included syndesmophytes in 34.7% and “bamboo spine” in 16.3% of patients. Acute anterior uveitis was noted in 44.9% of patients. Male sex was associated with involvement of shoulder (P = 0.001). Female sex and juvenile-onset AS were associated with extra-articular involvement. Positive HLA-B27 was associated with hip involvement (P = 0.042) and adult-onset AS (P = 0.035). Analysis of the patterns of disease in this population of 98 southern Iranian patients with AS revealed that female sex and juvenile-onset AS were associated with extensive extra-axial involvement; and HLA-B27 was associated with hip involvement. The study was conducted in Rheumatology Clinic of Hafez Hospital of Shiraz University of Medical Sciences, Shiraz, Iran.     

Prevalence of ossification of posterior longitudinal ligament in patients with ankylosing spondylitis

OBJECTIVE: To determine the prevalence of ossification of the posterior longitudinal ligament (OPLL) in patients with ankylosing spondylitis (AS). METHODS: A cross-sectional radiological examination was performed in patients diagnosed with AS. A bone and joint radiologist screened and confirmed the cervical radiographs of these patients. A review of the medical records was also conducted to investigate the relationship between the clinical manifestations and the actual expression of OPLL in patients with AS. RESULTS: Among 544 patients with AS, 470 (86.4%) were men and 96.1% were HLA-B27-positive. The mean age was 34.3 +/- 9.3 years and mean disease duration was 12.4 +/- 7.2 years. After reviewing the cervical radiographs, OPLL was found in 19 patients (3.5%; 95% CI 1.9, 5.0). The mean age of these 19 patients was 39.9 +/- 10.7 years, and the male to female ratio was 18:1. Interestingly, a statistically significant number of patients who expressed OPLL were older (p = 0.007). However, we were unable to determine whether OPLL was significantly associated with AS disease duration, peripheral arthritis, anterior uveitis/iritis, HLA-B27, anterior atlantoaxial subluxation, diffuse idiopathic skeletal hyperostosis, or other paraspinal ligament disorders. CONCLUSION: Our study showed that the frequency of OPLL in Korean patients with AS was 3.5%, which was considerably lower than previously reported values (15.5% in 103 Mexican AS). We were able to determine that OPLL in AS was associated with older age.     

LMP2 polymorphism is associated with extraspinal disease in HLA-B27 negative Caucasian and Mexican Mestizo patients with ankylosing spondylitis

OBJECTIVE: To determine the effects of HLA Class II genes, particularly LMP2 and previously implicated Class I genes, on susceptibility and disease expression in HLA-B27 negative ankylosing spondylitis (AS). METHODS: Patients included 41 HLA-B27 negative Caucasians from a total AS population of 546 and 17 HLA-B27 negative Mexican Mestizo. Controls included 4352 random HLA-B27 negative Caucasians. LMP2 genotype assignments were made on all patients and 282 random Caucasian controls by polymerase chain reaction-restriction fragment length polymorphism with the Cfo I restriction enzyme while HLA typing was performed on patients and controls using microcytotoxicity assays for Class I, and sequence specific probe-PCR for HLA-B60, B39, B38, and DR. RESULTS: The LMP2BB genotype was significantly decreased in Caucasian AS patients without extraspinal (ES) disease (25%) compared to AS patients with ES (64.7%) (p = 0.01) and random Caucasian controls (53.9%) (p = 0.007), even when those with colitis and psoriasis were excluded from analysis (ES+ 55.6% versus ES- 22.2%). This finding remained significant after stratification by HLA-DR. Similar trends were noted in the Mexican population. A potential role for HLA-DR8 and DR2 in susceptibility to disease was observed in Caucasian patients, although this observation requires confirmation. We could not confirm reported associations with HLA-B60 or B39. Peripheral arthritis was significantly more commonly observed in those who had had acute anterior uveitis (AAU) (75%) than in those who had not developed AAU (27.3%) (p = 0.04). CONCLUSION: HLA Class II encoded genes may have effects on disease susceptibility and/or phenotype in HLA-B27 negative individuals similar to those noted in HLA-B27 positive AS. Eccentric and axial phenotypes of disease may be immunogenetically determined.     

Prevalence of HLA-B27 in the general population and in patients with axial spondyloarthritis in Saudi Arabia

The prevalence of HLA-B27 in the general population and in axial spondyloarthritis (axSpA) patients in Saudi Arabia is unknown. The aim of this study was to evaluate the prevalence of HLA-B27 in these two populations and describe the delay in diagnosis of axSpA patients. The prevalence of HLA-B27 in the general population was evaluated using cord blood and healthy organ transplant donor databases. Data from patients with axSpA were collected retrospectively from five centers. Ankylosing spondylitis (AS) was diagnosed based on a positive X-ray, as evaluated by two independent readers. Patients with inflammatory bowel disease and psoriasis were excluded. A total of 134 axSpA patients were included, of whom 107 (79.9%) had AS, and most (67.2%) were males. HLA-B27 was positive in 60.4, 69, and 25.9% of patients with axSpA, AS, and non-radiographic axSpA (nr-axSpA), respectively. The median and interquartile range (IQR) ages at symptom onset and disease diagnosis were 26 (20–33) and 30 (25–38) years, respectively. The median delay to diagnosis was 3 (1–6) years. There was a negative correlation between the time of onset of symptoms and the delay in diagnosis (r = ?0.587). Male gender and HLA-B27 positivity were associated with a younger age at symptom onset/diagnosis (p < 0.05). HLA-B27 was positive in 82/3332 (2.5%) and 27/1164 (2.3%) individuals in the cord blood and healthy organ transplant donor databases, respectively. The prevalence of HLA-B27 is lower in the general Saudi population and in axSpA patients compared to Caucasians, thus, limiting its utility as a diagnostic criterion.     

Erkrankungsalter und Diagnoseverzögerung bei Spondylarthropathien

A questionnaire with 78 questions concerning the situation of ankylosing spondylitis (AS) sufferers in Germany was distributed to a representative 3000 out of the more than 14,000 patient members of the German AS society; 1614 patients (54%) responded. The age distribution of these patients roughly agrees with that expected due to the distribution of the age at diagnosis and the age distribution of the German population. The group of patients more than 65 years old is, however, under-represented. It turned out that at least 28% of the patients responding do not suffer from idiopathic AS but from other spondyloarthritides (spondylitic psoriasis, spondyloarthritis combined with Crohn's disease or ulcerative colitis). The distribution of the age at disease onset agrees well with that published in 1984 by van der Linden et al.: For 4% of the patients, the age at appearance of the first spondylitic symptoms was less than 15 years, for 90% it was 15-40 years and for the remaining 6% more than 40 years. The average age at disease onset was 25.6 years. The spondyloarthritides do not differ significantly in the distribution of the age at the first spondylitic symptoms. The distribution of the age at diagnosis did not differ significantly between male and female patients, in contrast to the findings by van der Linden et al. in 1984. The average age at diagnosis was 34.3 and 35.3 years for male and female patients, respectively. The resulting mean diagnosis delay for male and female patients was 8.4 and 9.8 years, respectively. Whereas the average diagnosis delay was still 15 years for patients with disease onset in the 1950s, it was only 71/2 years for patients with disease onset in 1975-79. It is not yet possible to predict if an average diagnosis delay less than 71/2 years results for patients with a disease onset later than 1980, because the number of further diagnoses to be expected for patients with disease onset in these years is not negligible. Twenty-six percent of the patients (22% of the males, 34% of the females) have relatives, likewise, suffering from AS. Whereas patients with familiar AS experience their first spondylitic symptoms, in the average, 11/2 years earlier than patients without relatives suffering from AS, the difference is 5 years for patients suffering from spondyloarthritis combined with ulcerative colitis. Reports written for patients on other results of the survey can be found in the newsletter "Bechterew-Brief" of the Deutsche Vereinigung Morbus Bechterew.     

The LMP2 polymorphism is associated with susceptibility to acute anterior uveitis in HLA-B27 positive juvenile and adult Mexican subjects with ankylosing spondylitis

INTRODUCTION—An association between polymorphism of the HLA linked LMP2 locus and the development of acute anterior uveitis (AAU) has previously been described in B27 positive white subjects with ankylosing spondylitis (AS). This study evaluated LMP2 alleles in two HLA-B27 positive Mexican populations of patients with spondyloarthropathy known to have a different clinical spectrum of disease from white people.
PATIENTS AND METHODS—The study populations consisted of 90 AS patients from Guadalajara with predominantly adult onset disease and 80 AS patients from Mexico City with predominantly juvenile onset disease. LMP2-CfoI amplified fragment length polymorphisms were determined after polymerase chain reaction amplification and digestion with CfoI restriction enzyme.
RESULTS—There was an increased LMP2A allelic frequency in patients who had had AAU in both Guadalajara (31.8%) and Mexico City (33.3%) when compared with non-AAU patients (15.2% and 17.7% of Guadalajara and Mexico City populations, respectively). The odds ratio relating LMP2A allelic frequency and AAU for the combined population, stratified by age at onset of disease, was 2.51 (p=0.01). LMP2 alleles did not influence the age at onset of disease or the development of peripheral arthritis.
CONCLUSIONS—These data support the view that polymorphism at the LMP2 locus is associated with the development of AAU in B27 positive subjects with AS. The requirement for both the less common LMP2 allele and HLA-B27 is consistent with the low prevalence of AAU in Mexican patients with spondyloarthritis.

     

Primary ankylosing spondylitis: patterns of disease in a Brazilian population of 147 patients

OBJECTIVE: To analyze patterns of disease in a population of Brazilian patients with primary ankylosing spondylitis (AS). METHODS: Retrospective study (1988-98) analyzing 147 patients with a diagnosis of primary AS according to the modified New York criteria. Selected patients had complete clinical (initial symptom, axial and peripheral involvement, heel enthesitis, extraarticular manifestations) and radiological (sacroiliac, lumbar, thoracic, and cervical spine) investigations, and these data were compared with sex, race, age at onset, and HLA-B27. RESULTS: There was a predominance of men (84.4%), Caucasian race (75.5%), adult onset (> 16 years, 85%), and positive HLA-B27 (78.2%). Family history of AS was noted in 14.3% of the patients. Pure axial AS was observed in 37 patients (25.2%). The predominant initial symptoms were inflammatory low back pain (61.9%) and peripheral arthritis (22.4%). Thoracic and cervical spine involvement was noted in 70.1% of the patients; radiological findings included syndesmophytes in 46.9% and "bamboo spine" in 20.4% of patients. The extraaxial joints most frequently involved were: ankles (39.5%), hips (36.1%), knees (29.3%), shoulders (19%), and sternoclaviculars (14.3%); heel enthesitis was present in 22.4%. Acute anterior uveitis was noted in 14.3% of patients. Male sex was associated with involvement of thoracic spine (p = 0.002), cervical spine (p = 0.002), and hips (p = 0.042), whereas female sex was associated with sternoclavicular (p = 0.024) involvement. Caucasian race presented higher frequency of positive family history (p = 0.023); there was no statistical significance of clinical and radiological variables compared with African-Brazilians. Juvenile onset AS presented higher frequency of ankle (p = 0.012) and knee (p = 0.001) involvement, heel enthesitis (p = 0.001), and total hip replacement (p = 0.038), whereas adult onset was associated with thoracic (p = 0.026) and cervical spine (p = 0.026) involvement and positive family history (p = 0.044). Positive HLA-B27 was associated with ankle involvement (p = 0.007) and heel enthesitis (p = 0.013). CONCLUSION: In this population women showed a milder axial involvement, Caucasian race presented axial and peripheral involvement similar to African-Brazilians, juvenile onset AS was associated with articular involvement of the lower limbs, and positive HLA-B27 was associated with ankle involvement.     

Undifferentiated spondyloarthropathies in Brazilians: importance of HLA-B27 and the B7-CREG alleles in characterization and disease progression

OBJECTIVE: To analyze the profile of the HLA-B27 and B7 cross-reactive group (CREG) alleles and the role of these markers in disease characterization and progression in patients with undifferentiated spondyloarthropathies (uSpA). METHODS: A total of 80 patients with a diagnosis of uSpA (40 HLA-B27 positive and 40 HLA-B27 negative) were prospectively studied for 2 years. The control group consisted of 66 HLA-B27 positive and 112 HLA-B27 negative individuals without a history of seronegative SpA. HLA-B alleles were typed at low (B7-CREG alleles, i.e., B*7, B*54, B*55, B*56, B*40, B*42) or high resolution (B*27 alleles) using polymerase chain reaction-amplified DNA hybridized with sequence-specific oligonucleotide probes. RESULTS: HLA-B*2705 was the most frequent allele, observed in 92.5% of the patients and in 77% of the controls, followed by the HLA-B*2702, observed in 5% of the patients and in 12% of the controls. HLA-B*2704 was observed in only one patient (2.5%), and was absent in the control population. HLA-B*2703 (6%) and HLA-B*2707 (5%) alleles were observed only in controls. No associations between HLA-B*27 alleles or B7-CREG alleles and any specific manifestation of uSpA were observed. HLA-B27 positive patients more frequently presented juvenile onset SpA (p = 0.002) and progression to ankylosing spondylitis (AS) (p = 0.03) than did HLA-B27 negative patients. The B7-CREG alleles were observed in 5% of the HLA-B27 positive uSpA group, in 25% of the HLA-B27 negative uSpA group, in 7% of the HLA-B27 positive controls, and in 13% of the HLA-B27 negative controls; a significant association was observed between the presence of the B7-CREG and the HLA-B27 negative uSpA group (p = 0.012). CONCLUSION: The frequency of the HLA-B*2705 allele among the B27 positive uSpA patients of this series was closely similar to that reported for patients with ankylosing spondylitis (AS). The presence of HLA-B*27 alleles was associated with the progression to AS, and the presence of B7-CREG was associated with uSpA in the HLA-B27 negative group.     

幼年发病型脊柱关节病的临床特征

目的　提高对幼年发病型脊柱关节病 (JSpA)的认识。方法　分析 190例JSpA患者的临床、实验室及放射学资料 ,并对幼年发病关节炎的诊断、分类和鉴别进行讨论。结果　 190例JS pA中 ,男性 16 3例 ,女性 2 7例 ,男女之比为 6∶1,发病年龄 3～ 16岁 ,平均 (12± 3)岁 ,8岁后发病 175例 ,占 92 1% ;15 7例 (82 6 % )患者首先出现的是外周关节炎 ,2 3例 (12 1% )以腰背痛为第一症状 ,病程中共有 187例 (98 4% )的患者出现了外周关节炎 ,12 3例 (6 4 7% )患者有或有过腰背疼痛史 ,外周关节炎与腰背疼痛出现的时间间隔 ,从同时发生到间隔 2 0年 ,平均 3 2年。 6 7例 (35 3% )有肌腱端炎的表现 ,2 0例 (10 5 % )腊肠指 (趾 ) ,9例虹膜炎。HLA B2 7的阳性率为 87 9% ,76 0 %有X线证实的骶髂关节炎。在 190例患者中 ,10 6例患者确诊幼年强直性脊柱炎 (JAS) ,此组患者平均病程 6 3年 ,明显长于JSpA组 (P <0 0 1)。 结论　JSpA的概念有助于提高对儿童关节炎的认识 ,半数以上JSpA患者约在发病 6 3年后发展为幼年强直性脊柱炎。     

Acute anterior uveitis,arthritides and enteric antigens

Summary One hundred and fourteen patients with acute anterior uveitis were studied for the presence of the HLA-B27 tissue type, the prevalence of spondylitis and arthritis and the occurrence of gastro-intestinal and urogenital infections or diarrhoeal illness in the history. Eighty-seven (76%) were B27+ and 27 (24%) B27-. Forty-two (48%) of the B27+group had ankylosing spondylitis (AS); 13 (30%) of them were females. Sacroilitis (SI) with no spinal involvement was present in 21 patients (24%), 13 (61%) males and 8 (38%) females. Peripheral arthritis occurred in 6 patients. Thus, 68 (78%) of the HLA-B27+positive patients had inflammatory spinal and/or joint disease, compared with 1 (4%) of the HLA-B27-group (p<0.001). The AS diagnosis was unknown previous to our examination in 31% of the males and 54% of the females, and SI was undiscovered in 61% of the males and 62% of the females. The occurrence of acute enteric infections was significantly increased in the B27+AAU group, compared with the B27-patients and the patients reported exacerbation of AAU in connection with episodes of diarrhoea. An increased occurrence of urogenital infections was shown only in cocomparison with the males of the B-27+AAU group. Thirty-three out of 47 AAU patients assayed by enzyme immuno-assay (EIA) for the quantification of IgM, IgA and IgG antibodies against Klebsiella pneumoniae, E coli, and Proteus mirabilis had significantly raised antibody titres against one or more of the antibodies studied, as compared to 62 healthy controls. Though there was no statistically significant difference between the B27+group and the B27-group suggesting that these antigens may also play a part in the pathogenesis of B27 negative AAU. These results confirm the previous findings that gut infections are important in the aetiology of AAU and AS, but other mechanisms than the immunological cross-reactivity with enteric bacteria require further examination.     

Increased level of HLA-B27 expression in ankylosing spondylitis patients compared with healthy HLA-B27-positive subjects: a possible further susceptibility factor for the development of disease

OBJECTIVE: In B27 transgenic rats, susceptibility to the development of a spondyloarthropathy-like disease has been shown to correlate with the level of B27 transgene expression on lymphoid cells. The aim of this work was to study HLA-B27 molecule expression in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) and from normal controls (NC). METHODS: Twenty B27(+) AS patients and 16 B27(+) NC were studied. HLA-B27 whole molecules and free heavy chains (HCs) and total HLA class I molecules were evaluated at the surface of PBMCs by immunofluorescence and flow cytometry. B27 subtypes were defined with the PCR-SSP (polymerase chain reaction-sequence-specific primer) technique. Cellular activation was evaluated by the expression of CD69, CD25 molecules and interferon gamma (IFN-gamma) production. RESULTS: B27 expression was 55,536.3+/-18,961.0 MESF (molecules of equivalent soluble fluorochromes) units in AS and 25,936.0+/-12,117.5 MESF in NC (P=0.00009), total HLA class I expression was 448,840.2+/-136,293.8 MESF in AS and 533,494.4+/-232,931.1 MESF in NC (not significant), HC expression was 10,593.4+/-6,396.1 MESF in AS and 14,843.0+/-7,544.2 MESF in NC (not significant). The higher B27 expression in the SA group was not due to higher cell activation as it was not correlated with CD69 and CD25 expression in PBMCs or with the level of IFN-gamma. HLA-B27 expression did not correlate with indexes of disease status [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI)]. CONCLUSIONS: We found greater expression of HLA-B27 molecules in patients with AS than in healthy subjects. This phenomenon was not accompanied by general up-regulation of HLA class I molecules or by greater expression of classical T-cell activation markers. On this basis we propose that the higher expression of the HLA-B27 molecules is a further predisposing factor for the development of AS.     

HLA antigens may influence the age of onset of psoriasis and psoriatic arthritis

OBJECTIVE: To analyze whether HLA antigens may influence the age of onset of both psoriasis and psoriatic arthritis (PsA). METHODS: One hundred thirty-five patients with PsA (77 men, 58 women, mean age 47 +/- 12 yrs) were analyzed. All were studied with a standard protocol and consecutively recruited to evaluate the relative contribution of HLA-Cw and HLA-B27 alleles to PsA susceptibility. Fifty patients with psoriasis alone were also recruited to analyze the role of HLA-Cw genes on disease susceptibility. HLA-Cw antigens were investigated by DNA based methods (PCR-SSOP), while HLA-B27 antigen was studied using serological methods, and their frequencies were compared to 177 healthy controls. RESULTS: In PsA Cw6+ patients, the mean age at psoriasis onset was 23 +/- 12 years compared to 32 +/- 12 years in Cw6- patients (p = 0.012). Age of arthritis onset was 35 +/- 13 years in Cw6+ patients versus 38 +/- 12 years in Cw6- patients (p = NS). In patients with psoriasis alone, the age at onset was 18 +/- 10 years in Cw6+ versus 30 +/- 11 years in Cw6- patients (p < 0.01). Cw6 correlated well with a positive family history of psoriasis among first-degree relatives (64% of patients with family history were Cw6+, whereas only 30% of those without family history had this allele (p < 0.05). The onset age of psoriasis in HLA-B27+ patients was 24 +/- 8 years vs 32 +/- 14 years in B27- patients (p = 0.026), whereas onset age of arthritis was 30 +/- 10 years in B27+ compared to an age of onset of 40 +/- 12 in B27- patients (p = 0.0056). CONCLUSION: Our results confirm the known association between Cw6, early onset psoriasis and positive family history (type I psoriasis). The association between HLA-B27 and earlier onset ages for both psoriasis and arthritis in PsA had not previously been emphasized. The HLA antigens may determine not only disease susceptibility, but also the age of disease onset in psoriasis and PsA.