类风湿性骨病与牙周炎的病因机制相关性研究进展

类风湿性骨性疾病大体包括类风湿性关节炎和强直性脊柱炎。这两种类风湿性骨病与牙周炎都是自身免疫相关性疾病,牙周炎人群中类风湿性骨病的发病率增加,类风湿性骨病患者牙周炎发病率同样增高。究其原因,牙周炎与类风湿性骨病在病因机制方面存在共同之处。本文就类风湿性骨病与牙周炎患病与治疗相关性,造成发病部位炎性表现和骨质改变的原因、机理进行综述。希望以此增加多学科的联合以及对牙周病的深入研究提供理论依据。     

The role of the gut and microbes in the pathogenesis of spondyloarthritis

The intestinal microbiota is firmly implicated not only in the pathogenesis of inflammatory bowel disease (IBD) but increasingly also in the development of inflammation at extraintestinal tissue sites. Significant clinical, genetic, immunological, and microbiological overlap exists between IBD and spondyloarthritis (SpA), which indicates that pathophysiological mechanisms are shared between these diseases and may center on the intestinal microbiota. Recently, culture-independent techniques have enabled the microbiota in health and disease to be described in increasing detail. Moreover, functional studies have identified myriad host effector and regulatory pathways that shape or are shaped by this microbial community. We consider the complex relationship between SpA pathogenesis and gut microbes, with a discussion of how manipulation of the gut microbiota itself may be a promising future target for SpA therapy.     

Bone formation in axial spondyloarthritis

The success of targeted therapies directed against tumor necrosis factor for patients with spondyloarthritis has shifted the focus of physicians and scientists towards the prevention of structural damage to the involved structures, in particular the sacroiliac joints and the spine, to avoid loss of function and disability. Structural damage to the skeleton as witnessed by radiography mainly consists of new bone formation potentially progressively leading to spine or joint ankylosis. This important long-term outcome parameter has been difficult to study, not alone because the time window for change may be long but also because human tissues with direct translational relevance are rarely available. Data from rodent models have identified growth factor signaling pathways as relevant targets. Both human and animal studies have tried to understand the link between inflammation and new bone formation. At the current moment, most evidence points towards a strong link between both but with the question still lingering about the sequence of events, disease triggers, and the interdependence of both features of disease. New discoveries such as a masterswitch T cell population that carries the IL23 receptor and the analysis of auto-antibodies directed again noggin and sclerostin are contributing to innovative insights into the pathophysiology of disease. Long-term data with tumor necrosis factor (TNF) inhibitors also suggest that some window of opportunity may exist to inhibit structural disease progression. All these data provide support for a further critical analysis of the available datasets and boost research in the field. The introduction of novel disease definitions, in particular the characterization of non-radiographic axial spondyloarthritis patients, will likely be instrumental in our further understanding of structural damage.     

Adverse effects of TNF inhibitors in SpA: Are they different from RA?

Tumor necrosis factor (TNF) inhibitors were the first biologic drugs prescribed for the treatment of spondyloarthritis (SpA) and rheumatoid arthritis (RA). Although they provide significant improvement of signs and symptoms, TNF inhibitors need to be used frequently for a long period of time. The analysis of the follow-up of the largest national biologics registries has shown that the most important adverse effect of TNF inhibitors is infection, which is significantly higher than the non-biologic treatment group; reactivation of latent tuberculosis is three to four times more frequent in patients using monoclonal antibodies than soluble receptors. The only cancer site more frequent to be associated with TNF inhibitors in RA and SpA is the non-melanoma skin cancer. Paradoxical reactions do occur during anti-TNF treatment mainly in SpA, such as new manifestations or flares of acute uveitis, new onset of psoriasis, such as palmoplantar pustulosis, or new onset or flares of inflammatory bowel disease, which occurs especially during etanercept treatment.     

英夫利西单抗谷浓度及抗体水平监测在维持治疗强直性脊柱炎患者中的临床应用

目的:探讨AS患者英夫利西单抗(IFX)谷浓度(TLs)与疗效的关系,了解抗IFX抗体(ATI)产生情况。方法:连续纳入2017年1月至2018年12月苏北人民医院接受IFX治疗的AS患者38例。在第8次应用IFX前空腹抽取检测血清IFX-TLs和ATI水平,在第1次、第6次、第8次应用IFX前进行AS病情活动度评分(ASDAS),采用单因素方差分析、秩和检验、χ^2检验、Logistic回归分析进行统计学分析。从而进行疗效评价。结果:①38例AS患者,其中6例(16%)出现了ATI。这6例患者第8次IFX给药(38周)时出现病情反弹。②以第8次IFX治疗相比第6次IFX治疗的ASDAS是否上升进行分组,绘制受试者工作曲线(ROC)曲线,计算出IFX-TLs维持在0.635μg/ml以上时,患者病情不易反跳。③Logistic回归分析结果显示IFX-TLs与BMI相关[OR(95%CI)=1.536(1.023,2.308),P=0.039],与合并用药相关[OR(95%CI)=0.218(0.06,0.797),P=0.021]。结论:ATI的产生以及IFX-TLs变化与IFX失应答密切相关,应定期监测,调整治疗方案。     

肿瘤坏死因子-α拮抗剂对类风湿关节炎和强直性脊柱炎患者血清白细胞介素-17和外周血 Th17细胞比例的影响

目的初步探讨外周血 Th17细胞亚群的比例以及 IL-17的表达水平在 RA 和 AS 患者接受 TNF-α拮抗剂治疗前后的改变及其意义。方法选择 RA 患者27例和 AS 患者22例,2种疾病中各有14例患者接受 TNF-α拮抗剂治疗40周。对照组24名来源于健康献血者。采用流式细胞术检测外周血 CD4+T 细胞中 Th17细胞亚群的比例,ELISA 检测外周血 IL-17表达水平。符合正态分布数据采用2个独立样本 t 检验,不符合正态分布则采用 Wilcoxon 秩和检验,患者治疗前后的比较采用配对 t 检验。结果治疗前,RA 和 AS 患者外周血 CD4+ T 细胞中 Th17细胞亚群的比例显著高于健康对照组[RA 1.03%（0.66%,1.78%）与健康对照0.50%（0.43%,0.67%）,Z=-3.236,P<0.01;AS（1.16±0.09）%与健康对照（0.59±0.06）%,t=5.226,P<0.01]。同样,IL-17的表达水平在2组疾病中也显著升高[RA（32.3±2.5） pg/ml,健康对照（14.3±2.5） pg/ml,t=5.070,P<0.01;AS 28.98（23.84,36.14） pg/ml,健康对照11.84（5.33,22.12） pg/ml,Z=-4.103,P<0.01]。 TNF-α拮抗剂治疗后,2组疾病 CD4+T 细胞中 Th17细胞亚群比例无明显变化[RA 驻（0.1045±0.2126）%;AS 驻（0.0025±0.1838）%],但 IL-17表达水平则明显下降[RA 驻（-13.5±5.0） pg/ml;AS 驻（-16.0±1.9） pg/ml]。结论 Th17细胞及其分泌的细胞因子 IL-17在 RA 和 AS 的发病机制中起重要作用,TNF-α拮抗剂对 AS 和 RA 患者 Th17细胞亚群炎症细胞因子的分泌功能有明显的抑制作用,但40周的治疗仍不能降低 Th17细胞比例,这可能是 TNF-α拮抗剂短期治疗后疾病复发的原因之一。