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.     

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.     

Thrombin generation in ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with an increase in cardiovascular risk. Thrombin generation is associated with the risk of thrombosis, and the endogenous thrombin potential (ETP) has been proposed as a parameter for plasma-based hypercoagulability. The aim of the study was to evaluate the risk of thrombosis in a group of AS patients in comparison to healthy subjects and to look for factors associated with an increased risk. Patients with AS fulfilling revised New York criteria were included in the study. Age, sex, disease duration, presence of peripheral arthritis and of extra-articular manifestation, and treatment were recorded, as well as HLA-B27 positivity, ESR, CRP, IgA, D-dimer levels, and bath ankylosing spondylitis disease activity index (BASDAI) score. Control patients were healthy blood donors. Patients with thrombosis history or with anti-thrombotic treatment were excluded. Endogenous thrombin generation was studied using a fluorometric technique (Technothrombin TGA kit, Technoclone, Austria). The thrombin generation parameters were ETP, corresponding to the area under the curve (nanomole per liter); lag time, corresponding to the initiation of the thrombin generation (minutes); maximal concentration of thrombin generated (Cmax, nanomole per liter); the time to reach the peak (Tmax, minutes); and the maximal rising slope of thrombin generation (velocity). Statistical analysis used Student’s t test for comparisons, and Spearman’s correlation test for the correlations; p values less than 0.05 were considered significant. Forty-six AS outpatients were included, 38 men with a mean (SD) age of 43.5 ± 13.1 years and a mean disease duration of 14.1 ± 8.4 years; ESR = 22.2 ± 17.2 mm, CRP = 14.5 ± 7.3 mg/l, and BASDAI = 37.8 ± 21.7 mm. Twelve had peripheral arthritis, and 17 had extra-articular involvement (IBD, uveitis, and psoriasis). Thirty-nine are HLA-B27 positive, 28 are under NSAIDs alone, and 15 were under TNF blockers at time of evaluation. Control group was 24 healthy blood donors. There is no difference between AS and controls for ETP, Cmax, and velocity. There is an increase in lag time (p = 0.03) and T max (p = 0.04) in AS patients. There is no difference in thrombin generation parameters between axial and peripheric AS, or between anti-TNF treated and not treated patients. Correlations were found between ETP and ESR (p = 0.006), CRP (p = 0.05), and BASDAI (p = 0.01); between Cmax and ESR, CRP, and BASDAI; between velocity and ESR; and between D-dimers and ESR and CRP. Even if there are some correlations between thrombin generation parameters and biological and clinical activity, this study does not demonstrate an increase in thrombin generation in patients with AS compared with controls. Moreover, the findings of higher lag time and Tmax in the patients may argue for a delayed thrombin generation in AS.     

Pulmonary involvement in ankylosing spondylitis

This is a prospective study analyzing 52 asymptomatic, consecutive patients with ankylosing spondylitis (AS), who submitted to a pulmonary investigation that included plain chest radiography, pulmonary function test (PFT), and thoracic high-resolution computed tomography (HRCT). The results were compared according to sex, race, dorsal spine involvement, thoracic diameter, smoking status, and HLA-B27. There were four patients (8%) with an altered plain chest radiograph. PFT presented a restrictive pattern in 52% of the patients. Thoracic HRCT showed abnormalities in 21 patients (40%), predominantly nonspecific linear parenchymal opacities (19%), lymphadenopathy (12%), emphysema (10%), bronchiectasis (8%), and pleural involvement (8%). Linear parenchymal opacities were associated with a smoking history (p=0.026) and dorsal spine involvement (p=0.032). HLA-B27 was not associated with any abnormality. A lower thoracic diameter was observed in patients with dorsal spine involvement (p=0.0001), restrictive pattern at PFT (p=0.023), and linear parenchymal opacities (p=0.015). The study concluded that nonspecific subclinical pulmonary involvement is frequent in AS.     

High frequencies of HLA-B27 in Chinese patients with suspected of ankylosing spondylitis

This study was performed to investigate the frequency of human leukocyte antigen (HLA)-B27 in Chinese patients with suspected of ankylosing spondylitis (AS) and to assess the clinical significance of HLA-B27 typing. A total of 1,016 patients suspected of AS were classified into six groups based on one major AS-related clinical manifestation. HLA-B27 was determined by polymerase chain reaction using sequence-specific primers. The frequency of B27 ranged between 24.3 and 46.7% among the patient groups, significantly higher than in healthy controls (2.4%). In the same group, the frequency of B27 in young (≤40 years) and in male patients was significantly higher than in the old and in female (P < 0.01). During a 1-year follow-up, 102 subjects were definitely diagnosed as AS, but only one B27(−) patient. Of the 102 definite patients, 69 (67.6%) definite patients were distributed in group 1 (low back pain and stiffness) with the higher incidence (28.5%) of AS. The incidence of AS in the same group was found with a similar pattern to the frequency of B27, in male and young patients significantly greater, except groups 4 and 6 (peripheral arthritis and alteration of skin). These findings confirm that HLA-B27 is one of sensitive diagnostic tools for early AS and suggest that there was a remarkable clinical significance of HLA-B27 typing in Chinese patients suspected of AS, particularly a young man who presents with low back pain and stiffness for >3 months.     

Clinical characteristics and medical management of Iranian patients with ankylosing spondylitis

Abstract

Objectives. Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease with variable clinical expression. Ethnic, racial and geographical factors have been associated with disease occurrence and expression. We intended to describe the clinical characteristics and assess the disease severity and treatment status in Iranian AS patients.

Methods. A total of 320 AS patients were assessed for demographic variables, clinical manifestations, human leukocyte antigen (HLA) status, disease severity, functional capacities, quality of life and treatment status.

Results. A gender ratio of 3.8:1, an average age onset of 27 ± 7.3 and a mean diagnostic delay of 8 years were observed. Eleven percent had juvenile onset AS. Positive family history was higher than that observed in most other countries. Enthesitis was a very common finding involving more than two-thirds of our patients. Uveitis was the leading extra-articular manifestation. We found an HLA-B27 prevalence of 73% and four HLA-B27 subtypes. Disease activity was high and the functional status was poor as indicated by mean Bath AS Disease Activity, Functional and Metrology indices. Quality of life was considerably impaired in our patients. We found a low percentage of patients on biological medications and a relatively higher percentage on disease modifying anti-rheumatic drugs and corticosteroids.

Conclusions. Our results demonstrate a broad characterization of Iranian AS patients providing a better understanding of this disease. A national multicenter registry would enable larger- scale prospective studies to be carried out further evaluating the disease burden on patients and society.     

Undifferentiated Spondyloarthropathies: A 2-Year Follow-up Study

The aim of the study was to analyse the 2-year follow-up of a series of patients with the diagnosis of undifferentiated spondyloarthropathy (uSpA). A prospective study was carried out analysing 68 patients with symptomatic uSpA who fulfilled the European Spondylarthropathy Study Group (ESSG) criteria for seronegative spondyloarthropathies (SpA) and were aged between 18 and 50 years. Inclusion criteria included inflammatory low back pain (ILBP) (without radiographic sacroiliitis), asymmetric oligoarthritis (predominantly affecting large joints in the lower limbs) and heel enthesopathies (Achilles tendinitis and/or plantar fasciitis). Imaging methods included pelvic radiography (at study entry and after 2 years) and calcaneal radiography (at study entry). There was a predominance of male gender (78%), caucasoid race (72%) and positive HLA-B27 (54%), with a mean age of 31 years and mean disease duration of 5 years. The first disease manifestations were ILBP (49%), asymmetric oligoarthritis (35%) and heel enthesopathies (16%). A positive family history of a definite SpA was mentioned by 9% of the patients. Seventeen patients (25%) scored 5 points in the Amor set of SpA criteria; logistic regression analysis showed that HLA-B27, heel enthesopathy and asymmetric oligoarthritis were significantly associated with Amor criteria ≥6, whereas ILBP was associated with Amor criteria <6. Male sex was associated with heel enthesopathies (p = 0.041) and ankle involvement (p = 0.015). Caucasoid race was associated with ILBP (p = 0.015) and buttock pain (p = 0.047). Positive HLA-B27 was associated with wrist involvement (p = 0.019) and Amor criteria ≥6 (p = 0.001). After a 2-year follow-up the following outcomes were observed: uSpA 75%; disease remission 13%; ankylosing spondylitis 10%; psoriatic arthritis 2%. Logistic regression analysis showed that buttock pain and positive HLA-B27 (trend) were statistically associated with progression to a definite SpA. In conclusion, uSpA can represent a provisional diagnosis in the group of SpA and a systematic follow-up is necessary in order to better establish the different patterns of the disease. Received: 2 June 2000 / Accepted: 5 January 2001     

Clinical features of ankylosing spondylitis may correlate with HLA-B27 polymorphism

The objective of this study is to investigate the relationship between clinical features of ankylosing spondylitis (AS) and HLA-B27 status or its subtypes. Clinical data and blood samples were collected with patients’ informed consent. Luminex liquid array combining polymerase chain reaction-sequence specific oligonucleotide probe was used to do the low-resolution HLA-B genotype typing. Polymerase chain reaction-sequence specific primer was applied to do the high resolution HLA-B27 typing. In 98 subjects, 93 were HLA-B27 positive, of which three subtypes were detected: B*2704 (n = 76), B*2705 (n = 12), and B*2715 (n = 5). The onset age for B27 negative and positive group was 28 ± 7.9 and 21.1 ± 6.2 years, respectively (χ² = −2.047, P = 0.041). The onset age for B*2704, B*2705 and B*2715 group was 20.45 ± 4.50, 26.67 ± 9.95 and 17.8 ± 11.12 years, respectively (χ² = 7.888, P = 0.019). No significant difference was found between B27 positive and negative group, or among three B27 subtypes groups for other clinical features. In conclusion, the clinical features of AS may be correlated with HLA-B27 status and its polymorphism.     

A survey of European and Canadian rheumatologists regarding the treatment of patients with ankylosing spondylitis and extra-articular manifestations

Ankylosing spondylitis (AS) is a disabling inflammatory disease accompanied by a variety of extra-articular manifestations in a significant number of patients. These manifestations, including Crohn’s disease, ulcerative colitis, psoriasis, and uveitis, share a similar inflammatory mechanism with one another and with AS. Extra-articular manifestations are observed in a larger percentage of patients with AS and spondyloarthritides (SpAs) than the normal population; therefore, it is important to identify these and other inflammatory-mediated conditions and consider them when treating SpAs. How rheumatologists approach patients with both AS and extra-articular manifestations may lead to a better understanding of what treatment approaches could be taken to optimize patient outcomes. Rheumatologists (N = 453) from five European countries and Canada who treat AS were surveyed to determine treatment practices and management of both AS and its associated extra-articular manifestations. Most rheumatologists (93%) believe AS could be diagnosed earlier as the average time between symptom onset and diagnosis was approximately 4 years. In total, 60% routinely screen patients with AS for extra-articular manifestations, although this varied considerably across countries. The majority (97%) agrees that controlling inflammation is critical during treatment, and patients with extra-articular manifestations tend to have poorer prognoses than those patients with only axial AS. Treatment considerations varied depending on whether patients presented with only axial AS or had extra-articular manifestations, where use of biologics became more common. Rheumatologists agree that patients with both AS and extra-articular manifestations require a different treatment strategy than patients with AS alone. Results of this survey highlight areas where rheumatologists differ in their clinical management of patients with AS including tools used for disease assessment and the routine screening, or lack thereof, for other inflammatory diseases. This evidence may suggest aspects within clinical practice where modifications may be made in order to optimize patient outcomes.     

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.     

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.     

Determination of HLA-B27 subtypes in Iranian patients with ankylosing spondylitis

The human leukocyte antigen-B27 is one of the class I molecules of the major histocompatibility complex which is strongly associated with ankylosing spondylitis (AS). The strength of the disease association with B27 varies markedly among racial and ethnic populations. It is an allele family, which constitutes about 31 subtypes, with a considerable geographic and ethnic difference in distribution. It is important to know whether certain subtypes show any preferential association with AS. Because there is no report regarding HLA-B27 subtypes in Iranian patients with AS, the main purpose of the present study was to assess the frequency of subtypes of human leukocyte antigen (HLA)-B27 in patients with ankylosing spondylitis in Iranian populationOne hundred and nineteen AS patients (82 HLA-B27 positive and 37 HLA-B27 negative) were selected for this study. HLA-B27 positive patients were screened by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) for B*27 subtyping.The results of present study revealed that only two subtypes were detected in Iranian patients, including B*2705 (52 patients, 63.4%) and B*2702 (30 patients, 36.6%). Our results showed a restricted number of HLA-B27 subtypes associated with AS in Iran and an elevated frequency of the B*2705 allele in these patients similar to other Euro-Caucasoid (Aryan) groups in the world.     

The high prevalence of infections and allergic symptoms in patients with ankylosing spondylitis is associated with clinical symptoms

Ankylosing spondylitis (AS) is strongly associated with the major histocompatibility complex (MHC) class I antigen HLA-B27. This may have influence on the physiologic immune response. Whether it leads to an increased prevalence of infections and/or allergy in AS patients is unclear. This study aims to determine the prevalence of infections and allergic symptoms in patients with AS and to detect a possible association with clinical symptoms. Data on 1,080 AS patients and on 102 disc prolapse patients were collected by questionnaire. The proportion of patients with a symptomatic infection in the last year was 65.5% in AS patients in comparison with 25.5% in disc prolapse patients (p=0.0001). AS patients reported more gastrointestinal (GI) [odds ratio (OR) 5.07, 95% confidence interval (CI) 2.20–11.71], urinary tract (OR 2.81, 95%CI 1.41–5.72), and respiratory (OR 5.83, 95%CI 3.38–10.08) infections than did disc prolapse patients. Multiple infections were more common in AS patients across all infection types. Allergic symptoms were reported by AS patients more frequently than by disc prolapse patients (OR 5.13, 95%CI 3.49–8.80). Patients reporting concurrent inflammatory bowel disease were more likely to report GI (OR 3.0, 95%CI 1.9–4.8) and urinary tract (OR 1.7, 95%CI 1–2.8) infection than primary AS patients. In AS patients, infection was independently associated with female gender (OR 1.96, 95%CI 1.47–2.56), a history of significant peripheral joint inflammation (OR 1.55, 95%CI 1.18–2.05), and increasing pain duration (p=0.05). A high prevalence of common infections and allergic symptoms is seen in patients with AS, most of which are HLA-B27-positive. This may have implications both for underlying mechanisms of disease and for therapeutic options.An erratum to this article can be found at     

Comparison of non-radiographic axial spondyloarthritis and ankylosing spondylitis patients in Malaysia

Aim of the workThis study aimed to compare the clinical features, associated comorbidities and treatment patterns of ankylosing spondylitis (AS) patient to those with non-radiographic axial spondyloarthritis (nr-axSpA) in Malaysia.Patients and methodsThis study was conducted in multiple rheumatology centre in Malaysia. Patients with axial spondyloarthritis (axSpA) were included. The AS and nr-axSpA group were compared.ResultsA total of 302 AS patients and 43 nr-axSpA patients were included. The age was comparable (41.7 ± 12.4 vs 38.5 ± 14.3 years; p = 0.13) however the male:female in those with AS was 4.8:1 vs 1.2:1 (p < 0.0001). The diagnostic delay was longer in AS patients (6.04 ± 6.6 vs 3.4 ± 7.3; p = 0.03), more were frequently smoking (50.3 % vs 25.6 %; p = 0.003), were Chinese (56.6 % vs 37.2 %; p = 0.02), had a higher frequency of HLA-B27 (p < 0.0001) and family history of axSpA (p = 0.04).More AS patients experienced inflammatory back pain (p < 0.0001), had higher Bath AS Metrology Index (BASMI) (p < 0.0001) and Bath AS functional index (BASFI) (p = 0.04). Nr-axSpA patients more likely to experience dactylitis (16.3 % vs 5.6 %; p = 0.014) but no significant differences in frequency of enthesitis. The frequency of comorbidities was similar in both groups. The use of non steroidal anti inflammatory drugs was more frequent in AS (p = 0.038) while nr-axSpA patients more likely to receive conventional disease modifying antirheumatic drug (p = 0.002).ConclusionAS and nr-axSpA shared some characteristics but also had some significant difference especially on gender, inflammatory back pain and HLA-B27. This study offers a better understanding of both the subtypes of axSpA in Malaysia.     

Demographic,clinical, and serological features of Turkish patients with rheumatoid arthritis: evaluation of 165 patients

The study was designed to describe demographic, clinical, serological, and radiological characteristics of patients with rheumatoid arthritis (RA) followed-up by a single institution. One hundred sixty-five patients, diagnosed as RA using ACR classification criteria, and followed-up in the rheumatology clinic between December 2005 and January 2010, were enrolled in the study. Of the patients, 125 were female, and 40 were male. Mean age of the patients was 52.5 years, and mean duration of the disease was 10.5 years. The most frequently involved joints were the wrist (95.2%), MCP (90.9%), and the PIP (92.6%). The knee and hip joint involvement rates were 44.8% and 23.6%, respectively. Patients (50.9%) were detected to have tenosynovitis. Involvement of the elbow joint was shown in 10.9% of the patients. The most common extra-articular manifestations were sicca symptom (40.6%) and carpal tunnel syndrome (35.7%), followed by pulmonary involvement (6.6%), vasculitis (3.6%), and Raynaud's phenomenon (1.2%). Rheumatoid nodules were detected in six patients (3.6%). One patient had Felty syndrome, and another patient had secondary amyloidosis. Patients (90.3%) had positive rheumatoid factor (RF), and 124 patients had positive anti-CCP antibody (75.2%). A more severe clinical course and a higher incidence of erosion, tenosynovitis, and deformities were detected in patients with anti-CCP antibody and positive RF (p = 0.03, p = 0.04, p = 0.01, p = 0.04, respectively). The wrist was the most frequently involved joint in our patients, and the most frequently seen extra-articular manifestation was sicca symptom. Presence of RF and anti-CCP antibody was associated with more severe disease including erosive and destructive arthropathy. Extra-articular involvement and presence of accompanying diseases increase the mortality.     

<Emphasis Type="Italic">IL1RN*2</Emphasis> allele of IL-1receptor antagonist VNTR polymorphism is associated with susceptibility to anklyosing spondylitis in Indian patients

Despite strong linkage of ankylosing spondylitis (AS) with human leukocyte antigen (HLA) B27, its contribution to disease susceptibility is only 15%, and additional genetic factors are likely to be involved in AS. Interleukin (IL)-1 locus has been linked to AS in European population. Thus, we studied IL-1 receptor antagonist polymorphism in Indian patients with AS. One hundred and sixty-two patients with AS and ethnically matched healthy controls were included. IL-1Ra variable number tandem repeat polymorphism was studied by polymerase chain reaction (PCR). HLA B27 was done by amplification refractory mutation system PCR. Clinical details regarding severity of articular disease, presence of peripheral arthritis, and extra-articular manifestations were collected. The mean age of these 162 patients was 35 years, and the mean duration of disease was 10.8 years. Of these162 patients, 137 were HLA B27 positive. The commoner alleles—IL-1RN*1 and IL-1RN*2—together accounted for 99.5% of the IL-1RN alleles in the control population and 98.5% of the cases. The allele frequency as well as the carriage rate of allele IL-1RN*2 were significantly higher in patients with AS than the control populations (26.3 vs 16.2% and 41.97 vs 22.5%, respectively; p = 0.015 and 0.0002). The IL-1RN*2 allele was not associated with any difference in clinical disease expression. The IL-1RN*2 allele is a susceptibility marker for AS in the Indian population but does not influence disease phenotype.     

HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom.

OBJECTIVE: To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. METHODS: HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically matched blood donors. RESULTS: The strong association of HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI) 135 to 218; p < 10(-99)). The association of HLA-B60 with AS was confirmed in HLA-B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p < 5 x 10(-5)), and a similar association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4; p < 0.05). No significant difference was observed in the frequencies of HLA-B27 allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HLA-B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles were detected. CONCLUSION: HLA-B27 and -B60 are associated with susceptibility to AS, but differences in HLA-B27 subtype do not affect susceptibility to AS in this white population.     

Clinical features and followup study of HLA-B27 positive patients presenting with peripheral arthritis

A comparison was made between HLA-B27 positive patients with peripheral arthritis and patients with ankylosing spondylitis (AS). The distribution of peripheral joint involvement in HLA-B27 positive seronegative arthritis was not the same as that in AS; significant differences were also noted in the sex ratio and incidence of uveitis. Followup of the patients with peripheral arthritis revealed that 25% had developed a further criterion for Reiter's syndrome, 45% had persistent seronegative arthritis and in 55% the arthritis had resolved.     

Coexisting ankylosing spondylitis and gouty arthritis

The aim of this study was to investigate the clinical characteristics of patients with coexisting ankylosing spondylitis (AS) and gout. Between July 1987, and October 2004, sixty-five patients with coexisting AS and gout were enrolled. The clinical manifestations of both AS and gout in these patients were studied. Of the 65 patients included in the study, 61 were men and four were women (men-to-women ratio, 15.3:1). Sixty-three subjects were Han Chinese, and two were Atayal Aborigines. Mean ages at onset of AS and gout were 29.3 ± 15.6 years (range 7–63) and 42.2 ± 13.2 years (range 20–74), respectively. Fifty-six patients developed gout after (15.5 ± 11.2 years; range, 1–51 years) onset of AS; nine patients developed gout before (average, 3.4 ± 2.2 years; range. 1–7 years) onset of AS. Forty-four (67.7%) patients had chronic peripheral arthritis and all 65 (100%) patients had acute peripheral arthritis. Thirty-three (50.8%) cases had heel pain (enthesopathy), including 22 (33.9%) with chronic heel pain, seven (10.8%) with acute heel pain, and four (6.2%) with concurrent acute and chronic heel pain. Sixty-one (93.9%) subjects were HLA-B27 antigen positive. Medical conditions potentially associated with hyperuricemia or gout were urolithiasis (n = 17), hypertension (n = 21), diabetes mellitus (n = 8), hyperlipidemia (n = 34), congestive heart failure (n = 6), coronary heart disease (n = 5), and stroke (n = 3). The following drugs were prescribed: diuretics (n = 7), low-dose aspirin (n = 4), antituberculous drugs (n = 1), and sulphasalazine (n = 34). Six (6.2%) patients had iatrogenic Cushing syndrome with adrenal insufficiency. Patients with coexisting AS and gout are not rare. Distinguishing between peripheral arthritis or enthesopathies of AS and gout is essential, especially when the course of AS arthritis becomes acute or the course of gout becomes chronic.     

Human leucocyte antigen‐B27 subtypes in Korean patients with ankylosing spondylitis: higher B*2705 in the patient group

Aim: To investigate the distribution of human leucocyte antigen (HLA) class I antigens and B27 subtypings in a group of B27(+) ankylosing spondylitis (AS) patients and a group of B27(+) control individuals, and to compare differences in their clinical features using subtyping. Methods: At otal of 143 B27(+) AS samples and 32 B27(+) control samples were collected consecutively from two rheumatology centres in South Korea. All patients were diagnosed according to the modified New York criteria for AS. Medical records of the patients were retrospectively reviewed for demographic information, Bath disease activity index (BASDAI) scores, laboratory parameters at diagnosis and extra‐articular manifestations. Polymerase chain reaction‐sequence‐specific primer typing for the B27 subtypes was performed using the Dynal HLA‐B27 high resolution kit. Results: Whereas subtypes in Korean AS patients include B*2704 (n = 11, 7.7%) B*2705 (n = 130, 90.9%), and B*2710 (n = 2, 1.4%), those of the control groups include B*2704 (n = 11, 34.4%), B*2705 (n = 19, 59.4%), B*2710 (n = 1, 3.1%), and B*2715 (n = 1, 3.1%). The proportion of B*2705 subtypes were significantly higher in the AS group than the control group (P < 0.01). There were no differences in clinical features (peripheral arthritis, uveitis, BASDAI scores) or laboratory parameters between the two groups. Conclusion: In Korean AS patients, not in the control group, the HLA‐B*2705 subtype was higher than other subtypes, in contrast to AS patients from Japan and China. B27 subtypes in AS patients were not associated with clinical features or laboratory parameters.