类风湿关节炎伴或不伴淀粉样变性患者的肿瘤坏死因子α、其可溶性受体I及-308基因启动子多态性：对反应性淀粉样变性中肾病和慢性病贫血发病机制的影响

Tumor necrosis factor alpha, its soluble receptor I, and -308 gene promoter polymorphism in patients with rheumatoid arthritis with or without amyloidosis: implications for the pathogenesis of nephropathy and anemia of chronic disease in reactive amyloidosis.

作者信息

Maury C P J, Liljeström M, Laiho K, Tiitinen S, Kaarela K, Hurme M

机构信息

University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

出版信息

Arthritis Rheum. 2003 Nov;48(11):3068-76. doi: 10.1002/art.11294.

DOI:10.1002/art.11294

PMID:14613268

Abstract

OBJECTIVE

To study tumor necrosis factor alpha (TNFalpha) -308 gene promoter polymorphism and circulating levels of TNFalpha and soluble TNF receptor type I (sTNFRI) in rheumatoid arthritis (RA) patients with and without reactive amyloidosis.

METHODS

In a retrospective study, we examined 55 RA patients with biopsy-proven reactive amyloidosis and 55 control RA patients without amyloidosis (matched for age, sex, rheumatoid factor titer, and RA duration). Inflammatory activity was assessed by measuring the erythrocyte sedimentation rate and C-reactive protein level. TNFalpha gene promoter polymorphism was studied using polymerase chain reaction-restriction fragment length polymorphism assay. Cytokine and receptor levels were measured by enzyme-linked immunoassays.

RESULTS

Patients with RA and amyloidosis had significantly higher TNFalpha and sTNFRI levels than did the control RA patients. The increased circulating levels of TNFalpha correlated with interleukin-18 levels, but not with the serum amyloid A protein levels or with TNFalpha -308 gene promoter polymorphism (reported to be associated with high TNFalpha levels and certain disease susceptibilities). In the patients with RA and amyloidosis, those with anemia had significantly higher TNFalpha and sTNFRI levels than did those without anemia, and circulating TNFalpha and sTNFRI levels correlated negatively with hemoglobin concentrations. In the patients with RA and amyloidosis, those with nephropathy had significantly higher TNFalpha and sTNFRI levels than did those without nephropathy; in patients with isolated proteinuria (but no creatinine elevation) the TNFalpha level was also significantly increased, indicating that the TNFalpha elevation was not merely a consequence of impaired renal function.

CONCLUSION

This study shows that circulating levels of TNFalpha and sTNFRI are significantly increased in RA patients with amyloidosis as compared with control RA patients without amyloidosis and that the increased levels may be implicated in the pathogenesis of certain disease manifestations, including anemia of chronic disease and renal pathology in reactive amyloidosis.

摘要

目的

研究伴有或不伴有反应性淀粉样变的类风湿关节炎（RA）患者肿瘤坏死因子α（TNFα）-308基因启动子多态性以及TNFα和可溶性肿瘤坏死因子I型受体（sTNFRI）的循环水平。

方法

在一项回顾性研究中，我们检查了55例经活检证实有反应性淀粉样变的RA患者和55例无淀粉样变的对照RA患者（根据年龄、性别、类风湿因子滴度和RA病程进行匹配）。通过测量红细胞沉降率和C反应蛋白水平评估炎症活动。使用聚合酶链反应-限制性片段长度多态性分析研究TNFα基因启动子多态性。通过酶联免疫吸附测定法测量细胞因子和受体水平。

结果

伴有淀粉样变的RA患者的TNFα和sTNFRI水平显著高于对照RA患者。TNFα循环水平升高与白细胞介素-18水平相关，但与血清淀粉样蛋白A水平或TNFα -308基因启动子多态性无关（据报道后者与高TNFα水平和某些疾病易感性相关）。在伴有淀粉样变的RA患者中，贫血患者比无贫血患者的TNFα和sTNFRI水平显著更高，且TNFα和sTNFRI循环水平与血红蛋白浓度呈负相关。在伴有淀粉样变的RA患者中，肾病患者比无肾病患者的TNFα和sTNFRI水平显著更高；在单纯蛋白尿（但肌酐无升高）患者中，TNFα水平也显著升高，表明TNFα升高不仅仅是肾功能受损的结果。