强直性脊椎炎骶髂关节早期改变的MRI诊断

目的:探讨强直性脊柱炎(AS)骶髂关节(SIJ)早期改变的MRI表现及诊断。方法:回顾性分析经病理证实的50个AS骶髂关节早期改变的MRI表现。结果:MRI显示47个SIJ滑膜软骨异常,在这些关节中骨髓水肿、骨髓内脂肪沉积分别有45、28个,骨质侵蚀及骨质硬化各有15、6个。MRI动态增强发现在这47个滑膜软骨异常的关节中,30个轻度强化,17个明显强化。3个关节MRI未见异常,动态增强示这3个关节无异常强化。结论:关节滑膜软骨异常、骨髓水肿、脂肪沉积等是AS骶髂关节早期改变的MRI重要征象,可作为MRI诊断早期AS的依据。     

Studies on the Major Histocompatibility System in Patients with Ankylosing Spondylitis

One hundred % of 66 patients with pelvospondylitis were found to have HL-A27 , whereas the frequency of the antigen in 60 patients with sacroiliitis was 70 %. The difference in frequency of HL-A27 between the two patient groups is statistically highly significant. This implies that tissue typing could be of clinical importance for a prognostic evaluation of patients with sacroiliitis.
Studies in families with several HL-NMLC identical sibs indicated a relatively low penetrance of disease in those carrying the gene for increased susceptibility to development of AS. No assocation of AS to particular MLC alleles was found either in families or in several SD-2 identical AS patients.     

强直性脊柱炎患者血清IL-17含量初步分析

目的：通过检测强直性脊柱炎患者血清IL-17水平变化,探讨IL-17在强直性脊柱炎发病中的作用。方法：用ELISA检测62例强直性脊柱炎患者血清IL-17含量。结果：强直性脊柱炎患者血清IL-17水平非常显著地高于正常对照组（P〈0.001）。结论：IL-17在强直性脊柱炎的发病中发挥着重要作用。     

Human Lymphocyte Antigen, HL–A27, in Japanese Patients with Ankylosing Spondylitis

A high association of HL–A27 specificity with ankylosing spondylitis was found in Japanese patients in spite of a very low frequency of this specificity in a normal Japanese population. These findings coincide well with those in Caucasian patients, and indicate the strong relationship between the susceptibility to ankylosing spondylitis and HL–A27 specificity beyond racial differences.
No particular HL–A patterns were noted in patients with the ossification of the posterior longitudinal ligament of the cervical vertebrae. This observation provides an evidence that this disease is etiologically different from ankylosing spondylitis.     

强直性脊柱炎患者血清Dickkopf-1蛋白水平分析

目的:分析强直性脊柱炎(AS)患者血清Dickkopf-1蛋白(DKK-1)水平变化并探讨其临床应用价值。方法:选取2016-12—2018-06我院诊治的50名AS患者[AS组,其中21例患者使用肿瘤坏死因子-α(TNF-α)抑制剂治疗(使用TNF-α抑制剂治疗组),29例患者未使用TNF-α抑制剂治疗(未使用TNF-α抑制剂治疗组)],另选取同期50名健康体检者为健康对照(对照组)。检测两组患者血清DKK-1、红细胞沉降率(ESR)和C-反应蛋白(CRP)水平。比较AS组患者治疗前后疾病活动度BASDAI、DKK-1、ESR及CRP水平变化。同时分析AS患者DKK-1与BASDAI、ESR及CRP的相关性。结果:AS组患者血清DKK-1水平明显低于对照组(P<0.01)。治疗6个月后,AS患者各亚组BASDAI、ESR及CRP水平较治疗前明显下降(P<0.01),且使用TNF-α抑制剂治疗组较未使用TNF-α抑制剂治疗组下降更明显(P<0.01);两组DKK-1水平与治疗前差异均无统计学意义(P>0.05)。AS患者各亚组血清DKK-1与BASDAI、ESR和CRP水平均无明显相关性。结论:DKK-1可能参与AS的新骨形成。TNF-α抑制剂可能对AS新骨形成无阻止作用。     

Phenotype Difference between Familial and Sporadic Ankylosing Spondylitis in Korean Patients

Clustered occurrences of ankylosing spondylitis (AS) in family have been noticed. We evaluated patients with AS confirmed by the modified New York criteria for familial history of AS (one or more first to third degree relatives). The clinical characteristics and the recurrence risks (number of AS patients/number of familial members) of the familial AS compared to sporadic AS were investigated. Out of a total of 204 AS patients, 38 patients (18.6%) reported that they had a familial history of AS. The recurrence risks in the familial AS patients for first, second and third degree family members were 14.5%, 5.2%, and 4.4% respectively. Erythrocyte sedimentation rate (ESR) (22.6±22.2 vs 35.4±34.4, P=0.029) and C-reactive protein (CRP) (1.24±1.7 vs 2.43±3.3, P=0.003) at diagnosis, body mass index (21.9±2.7 vs 23.7±3.3, P=0.002) and frequency of oligoarthritis (13.2% vs 33.7%, P=0.021) were significantly lower in the familial form. The presence of HLA-B27 (97.4% vs 83.1%, P=0.044) was significantly higher in familial AS. In conclusion, Korean familial AS patients show a lower frequency of oligoarthritis, lower BMI, lower ESR and CRP at diagnosis and higher presence of HLA-B27.

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强直性脊柱炎患者HLA-B27和免疫指标检测的临床意义

目的:探讨HLA-B27和免疫指标在强直性脊柱炎(AS)患者的临床意义.方法:采用流式细胞术检测147例AS患者、95例正常对照者的HLA-B27、CD3 T、CD4 T、CD8 T、CD19 B,用免疫比浊法检测IgA、IgG和IgM.结果:AS患者HLA-B27、CD3 T、CD4 T淋巴细胞的百分率及CD4 /CD8 的比值、血清IgA、IgG均明显高于正常对照组(P＜0.01);CD8 T淋巴细胞的百分率低于正常对照组(P＜0.05);CD19 B淋巴细胞的百分率高于正常对照组(P＜0.05);IgM与正常对照组相比无显著性差异.结论:HLA-B27、CD3 T、CD4 T与AS密切相关,提示,HLA-B27与CD3 T、CD4 T、CD4 /CD8 的比值可作为AS辅助诊断指标.     

强直性脊椎炎与细菌感染的关系初步研究

本文同时检测了正常人和强直性脊椎炎患者血清中抗３种细菌的抗体水平。结果显示：ＡＳ病人血清中抗肺炎克雷白菌和福氏志贺菌的抗体水平显著高于正常对照组，且这两种抗体的升高之间无相关性；抗鼠伤寒沙门菌的抗体水平则与正常人无显著差异。提示肺炎克雷白菌和福氏志贺菌可能在强直性脊椎炎的发病中起作用。     

Cost-of-Illness and Quality of Life in Patients with Ankylosing Spondylitis at a Tertiary Hospital in Korea

The objectives of this study were to estimate the cost-of-illness (COI) and health-related quality of life (HRQOL) in patients with ankylosing spondylitis (AS) in Korea and to evaluate the effects of socio-demographic and clinical factors on the COI and the HRQOL. Face-to-face interview surveys were taken from patients with AS at the Rheumatology Clinic of Seoul National University Hospital. Direct medical and non-medical costs, indirect costs (productivity loss due to job loss and sick leave), and deterioration of HRQOL in patients with AS were measured. Factors associated with COI and HRQOL were analyzed with multiple regression and multivariate logistic regression. A total of 191 patients with AS was enrolled in the study. The COI in patients with AS amounted to 11,646,180 Korean Won (KRW) per patient, and their HRQOL was 0.62. As functional severity worsened, the total costs increased (class I, KRW 7.7 million; class II, KRW 12.9 million; classes III & IV, KRW 25.2 million) and the HRQOL scores decreased (class I, 0.72; class II, 0.61; classes III & IV, 0.24). Functional severity is the major determinant of the COI and HRQOL in patients with AS.

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Drug Survival Rates of Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

We investigated the compliance of Korean patients using tumor necrosis factor (TNF) inhibitors to treat rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and identified potential predictors associated with treatment discontinuation. The study population comprised 114 RA and 310 AS patients treated with TNF inhibitors at a single tertiary center for at least 1 yr from December 2002 to November 2011. Of the 114 RA patients, 64 (56.1%) discontinued their first TNF inhibitors with a mean duration of 18.1 months. By contrast, 65 of 310 patients (21.0%) with AS discontinued their first TNF inhibitors, with a mean duration of 84 months. Although the survival rate did not differ among the three TNF inhibitors in the AS patients, the etanercept group had a lower discontinuation rate than the infliximab group in the RA patients. In addition, RA patients who received corticosteroids in combination with TNF inhibitors were more likely to discontinue their TNF inhibitors. The independent predictors of drug discontinuation in AS patients were male gender and complete ankylosis on radiographs of the sacroiliac joint. Our results provide further evidence that real-life treatment outcomes of RA and AS patients may be different from those observed in randomized clinical trials.

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强直性脊柱炎发病机制的遗传学研究

强直性脊椎炎是由遗传因素主导的疾病,HLA-B27基因与之有很强的关联,很多其他的基因也被证实对其发病有或多或少的影响.本文仅就强直性脊椎炎所涉及的相关基因及其可能的发病机制作一综述.     

中药浴对强直性脊柱炎患者甲襞微循环的影响

对８６例强直性脊柱炎患者于中药浴前后进行甲襞微循环观察，结果表明中药浴可明显改善微循环障碍（Ｐ＜０．０１），增快血流速度（Ｐ＜０．０１），解除红细胞聚集（Ｐ＜０．０１）。     

Serum Levels of OPG,RANKL, and RANKL/OPG Ratio in Patients with Ankylosing Spondylitis: A Systematic Review and Meta-analysis

Objectives: To investigate the role of osteoprotegerin (OPG), receptor activator of nuclear factor-kB ligand (RANKL), and RANKL/OPG ratio in the pathogenesis of ankylosing spondylitis (AS).

Methods: Studies that compared serum levels of OPG, RANKL, and RANKL/OPG ratio between AS patients and healthy controls were gathered. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated by the random-effects model.

Results: Twenty studies containing 1592 AS patients and 1064 healthy controls were included in this meta-analysis. Serum levels of OPG, RANKL, and RANKL/OPG ratio in AS patients were significantly higher than that in normal controls (OPG: SMD = 0.401, 95%CI = 0.026–0.777, p = 0.036; RANKL: SMD = 1.116, 95%CI = 0.510–1.723, p < 0.001; RANKL/OPG ratio: SMD = 0.691, 95%CI = 0.084–1.299, p = 0.026, respectively). Subgroup analysis suggested that Asian AS patients and patients with elevated ESR (ESR >20 mm/h) had higher serum OPG levels compared to normal controls. Asian patients, CRP >10 mg/L, ESR >20 mm/h, duration of disease ≤8 years, and BASDAI score >4 points subgroups showed increased RANKL levels compared to controls.

Conclusions: Serum levels of OPG, RANKL, and RANKL/OPG ratio may be used as potential susceptible biomarkers for AS, but they could be influenced by race, inflammatory factors, and disease activity of AS patients.     

Phenotype of Resting and Activated Monocyte-Derived Dendritic Cells Grown from Peripheral Blood of Patients with Ankylosing Spondylitis

Decreased levels of class II major histocompatibility complex (MHC) expression and impaired formation of immunological synapse by dendritic cells (DCs) of HLA-B27 transgenic rats have been recently demonstrated. The resulting dysfunction of DCs may be implicated in the pathogenesis of the HLA-B27-related disease in transgenic animals. The phenotype of DCs in patients with ankylosing spondylitis (AS) has not been evaluated. Monocyte-derived DCs (MDDCs) were grown from patients with active AS and age-matched healthy volunteers. Surface expression of HLA-DR, co-stimulation molecules CD80, CD86 and CD40, as well as CD83 was assessed by flow cytometry and compared between the groups under 3 conditions: in resting state, after stimulation by lipopolysaccharide (LPS) and after stimulation by LPS in the presence of etanercept, a soluble receptor of tumor necrosis factor α. Lower baseline expression of class II MHC molecules (HLA-DR) was observed by MDDCs grown from AS patients, as compared to healthy subjects. Post-stimulated levels of HLA-DR were comparable in both groups, suggesting greater up-regulation of class II MHC molecules by MDDCs from AS in response to LPS. No difference between groups in the levels of expression of co-stimulation molecules and CD83 was observed. Lower basic expression of class II MHC by the MDDCs grown from patients with AS may be associated with impaired regulation of their activity. Functional studies on DCs from patients with AS are needed to evaluate the integrity of their antigen-presenting function.     

强直性脊柱炎中TNF-α-850位点的单核苷酸多态性研究

目的：在中国吉林地区人群中探索6号染色体短臂上的加A基因区域内是否存在与强直性脊柱炎（AS）相关的新易感基因。方法：采集中国吉林地区79例强直性脊柱炎患者和132例正常对照者的外周抗凝血，在加A基因区域内选取11个SNPs多态位点，对单个位点的基因型频率和等位基因频率分布进行case-control分析。结果：中国吉林地区TNF-α-850多态位点的CC、CT和TT三种基因型在AS组和正常对照组中的分布差异具有统计学意义（P=0．027）。等位基因C和T在AS组和正常对照组中的分布差异更为显著（P=0．002）。HLA-B27阳性率在中国吉林地区AS组和正常对照组中的分布差异极其显著（χ^2=155．264，P=0．000）。对HLA-B27和TNF-α-850两位点的基因互助分析表明，与单独加A-B27阳性比较，当TNF-α-850T等位基因存在时OR值明显增加。结论：TNF-α-850C→T突变在中国吉林地区人群中可能增加AS的患病风险。     

Polymorphisms of KIRs Gene and HLA-C Alleles in Patients with Ankylosing Spondylitis: Possible Association with Susceptibility to the Disease

INTRODUCTION: An emerging body of evidence is accumulating to suggest that killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands contribute to the pathogenesis of diverse kinds of autoimmune diseases. However, the functional effects of their polymorphism remain largely unknown to date. Thus, the present study was undertaken to determine the association of the polymorphisms KIRs gene and HLA-C alleles with the susceptibility to ankylosing spondylitis (AS) by means of polymerase chain reaction/sequence-specific primers for genotyping KIRs from genomic DNA of 119 patients with AS together with 128 healthy donors as a control group. RESULTS AND DISCUSSION: We found that the frequencies of KIR3DS1 and KIR2DL5 were statistically significantly higher in the patient group than those in the control group (P = 0.016 and P = 0.003, respectively). Meanwhile, the percentage of patients, who were carrying two or more of the activating KIRs, was higher than that of control group. With respect to HLA-C alleles, individuals with AS showed an increased frequency of HLA-Cw02. If HLA-C was divided into group 1 or group 2 based on whether there was an asparagine or lysine present at position 80 of the alpha-chain, HLA-C group 2 was more common in subjects with AS compared to control subjects. The genotype 2DS1+/HLA-C lys(80)+ was more common in subjects with AS. Moreover, the CD69 expression, a NK activation marker, remarkably increased in patient with AS. CONCLUSION: In conclusions, this study suggests that KIR3DS1 may severe as AS susceptive genes to trigger continuous injury of arthrosis. The imbalance of activating and inhibitory KIR as well as HLA-C group 1 and group 2 may be the key factor, which influences the pathogenesis of AS. Moreover, KIR2DS1 might associate with the susceptibility of AS by influencing NK cell activity once group 2 HLA-C ligands are present.     

Clinical Characteristics of Patients With Psoriatic Spondylitis Versus Those With Ankylosing Spondylitis: Features at Baseline Before Biologic Therapy

BackgroundClinical characteristics and manifestations of psoriatic arthritis (PsA) have been extensively studied in western countries, yet data of Korean patients with PsA are very limited. We aimed to investigate the clinical traits of patients with PsA and dissect the characteristics of those with axial involvement.MethodsIn this observational study, we analyzed clinical data of 109 patients with PsA who were enrolled in the Korean College of Rheumatology Biologics and Targeted Therapy registry between December 2012 and March 2022 at the time point of initiating or switching to a biologic agent. Data from 2,221 patients with ankylosing spondylitis (AS) registered during the same period were also analyzed. We divided patients with PsA into patients with or without axial involvement and then added AS patients with psoriasis (total three subgroups) for comparative analyses.ResultsAsymmetric oligoarthritis was the most common clinical manifestation in patients with PsA, followed by symmetric polyarthritis and spondylitis. Our analysis indicated that methotrexate and sulfasalazine were the two most prescribed disease-modifying antirheumatic drugs for patients with PsA before starting biologic therapy. The patients with psoriatic spondylitis had more peripheral joint involvement (P = 0.016), less prior uveitis (P < 0.001), and lower human leukocyte antigen B27 (HLA-B27) positivity (P < 0.001) than the AS patients with psoriasis. Furthermore, syndesmophytes and radiographic sacroiliitis were prevalent among patients with PsA and AS patients with psoriasis who had the HLA-B27 gene.ConclusionOur study shows that the degree of peripheral arthritis is less severe in Korean patients with PsA who require biologics and reestablishes that psoriatic spondylitis is a common and important clinical pattern in Korean patients with PsA.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01965132","term_id":"NCT01965132"}}NCT01965132     

Clinical and Radiographic Features of Adult-onset Ankylosing Spondylitis in Korean Patients: Comparisons between Males and Females

The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4±8.9 yr and average disease duration was 9.6±6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober''s test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment.