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甘露糖结合凝集素在类风湿关节炎中的双重作用:一项横断面研究

Two edged role of mannose binding lectin in rheumatoid arthritis: a cross sectional study.

作者信息

Garred P, Madsen H O, Marquart H, Hansen T M, Sørensen S F, Petersen J, Volck B, Svejgaard A, Graudal N A, Rudd P M, Dwek R A, Sim R B, Andersen V

机构信息

Tissue Typing Laboratory, Department of Clinical Immunology, The National University Hospital (Rigshospitalet), Copenhagen, Denmark.

出版信息

J Rheumatol. 2000 Jan;27(1):26-34.

Abstract

OBJECTIVE

We investigated whether polymorphisms in the gene of mannose binding lectin (MBL) may be associated with onset of rheumatoid arthritis (RA), and whether MBL in conjunction with aggregated agalactosyl IgG (IgG-G0) may be associated with clinical and paraclinical variables.

METHODS

MBL genotypes and serum concentrations were measured by polymerase chain reaction and ELISA in 189 patients with established RA. Binding of purified MBL to IgG-G0 in serum was assessed and clinical and paraclinical variables were recorded.

RESULTS

The median age at onset of RA in the 3 genotypes (normal: A/A, hetero: A/0, and homozygous: 0/0 for variant alleles) was 54.1 (n = 108), 47.0 (n = 68), and 38.4 years (n = 13), respectively (p = 0.01). The frequency of variant alleles in patients with onset below the median age (50.8 yrs) was 0.32, but was 0.17 in patients with onset above 50.8 years (p = 0.003) and 0.20 in 250 controls (p = 0.001). Stratification according to erosion score (no, small, large) revealed an increasing tendency among the different groups in binding of MBL to IgG-G0, increased Health Assessment Questionnaire score, and acute phase reactants in A/A individuals, while no difference was seen among carriers of variant alleles. This effect was most pronounced in those with late onset RA.

CONCLUSION

Presence of MBL variant alleles was associated with early onset of RA. MBL deficiency may, therefore, accelerate the disease. However, in patients with late onset and advanced disease our results indicate that the A/A type may be associated with additional inflammation different from that seen in carriers of variant alleles.

摘要

目的

我们研究了甘露糖结合凝集素(MBL)基因多态性是否可能与类风湿关节炎(RA)的发病相关,以及MBL与聚集的无半乳糖IgG(IgG-G0)联合是否可能与临床及副临床变量相关。

方法

采用聚合酶链反应和酶联免疫吸附测定法检测189例确诊RA患者的MBL基因型和血清浓度。评估纯化的MBL与血清中IgG-G0的结合情况,并记录临床及副临床变量。

结果

3种基因型(正常:A/A,杂合:A/0,纯合:变异等位基因0/0)的RA发病中位年龄分别为54.1岁(n = 108)、47.0岁(n = 68)和38.4岁(n = 13)(p = 0.01)。发病年龄低于中位年龄(50.8岁)的患者中变异等位基因频率为0.32,而发病年龄高于50.8岁的患者中为0.17(p = 0.003),250名对照者中为0.20(p = 0.001)。根据侵蚀评分(无、小、大)分层显示,不同组中MBL与IgG-G0的结合、健康评估问卷评分增加以及A/A个体的急性期反应物呈上升趋势,而变异等位基因携带者之间无差异。这种效应在晚发型RA患者中最为明显。

结论

MBL变异等位基因的存在与RA的早发相关。因此,MBL缺乏可能会加速疾病进展。然而,在晚发和病情进展的患者中,我们的结果表明A/A型可能与不同于变异等位基因携带者的额外炎症相关。

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