a Laboratory of Immunopathology , Clinical Hospital, Federal University of Paraná , Curitiba , Brazil.
b Evangelic University Hospital of Curitiba , Curitiba , Brazil.
Autoimmunity. 2017 Nov;50(7):409-413. doi: 10.1080/08916934.2017.1373765. Epub 2017 Sep 12.
To investigate the association between mannose-binding lectin (MBL) serum level and MBL2 polymorphisms, and the frequency of spontaneous miscarriages in rheumatoid arthritis (RA) patients.
One hundred seventy seven women (mean age 50 years) with RA from Southern Brazil were studied and 4.5% had a history of abortion (8/177). The MBL levels were determined by ELISA. MBL2 polymorphisms in the promoter (-550H/L, -221X/Y), 5' untranslated region (4 P/Q) and exon 1 (p.Gly54Asp: B allele, p.Arg52Cys: D allele and p.Gly57Glu: C allele; collectively labelled O) were genotyped by sequencing.
Mannose-binding lectin levels of RA patients ranged from ≤100 ng/mL to 6640 ng/mL (median 541.5 ng/mL). There was a significant difference in MBL median levels (100 ng/mL vs. 625 ng/mL, respectively, p = .001) and frequency of MBL deficiency (75.0% vs. 24.1%, p = .007, OR = 10.3, 95%CI = 1.9-55.4), in patients with a history of miscarriage vs those without it. Patients with RA and miscarriage had more frequently haplotypes related with low MBL levels (p = .007, OR = 10.5, 95%CI = 1.3-84) than high producers. Moreover, LYPB haplotype and O allele were significantly associated with the occurrence of miscarriage (p = .001, OR = 9.7, 95%CI = 2.4-39.1 and p = .009, OR = 5.9, 95%CI = 1.4-23.4, respectively).
The results suggest that MBL deficiency and the presence of MBL2 gene polymorphisms that lead to MBL deficiency are risk factors for the occurrence of miscarriage in patients with RA.
探讨甘露聚糖结合凝集素(MBL)血清水平与 MBL2 多态性及自发性流产频率在类风湿关节炎(RA)患者间的相关性。
本研究纳入了来自巴西南部的 177 名女性 RA 患者(平均年龄 50 岁),其中 4.5%(8/177)有流产史。采用 ELISA 法测定 MBL 水平。通过测序对 MBL2 启动子(-550H/L、-221X/Y)、5'非翻译区(4P/Q)和外显子 1(p.Gly54Asp:B 等位基因、p.Arg52Cys:D 等位基因和 p.Gly57Glu:C 等位基因;统称 O)多态性进行基因分型。
RA 患者 MBL 水平范围为≤100ng/ml 至 6640ng/ml(中位数 541.5ng/ml)。有流产史和无流产史的患者 MBL 中位数水平(分别为 100ng/ml 和 625ng/ml,p=0.001)和 MBL 缺乏频率(分别为 75.0%和 24.1%,p=0.007,OR=10.3,95%CI=1.9-55.4)存在显著差异。与高 MBL 产生者相比,RA 合并流产的患者更常出现低 MBL 水平相关的单倍型(p=0.007,OR=10.5,95%CI=1.3-84)。此外,LYPB 单倍型和 O 等位基因与流产的发生显著相关(p=0.001,OR=9.7,95%CI=2.4-39.1 和 p=0.009,OR=5.9,95%CI=1.4-23.4)。
结果提示 MBL 缺乏和导致 MBL 缺乏的 MBL2 基因多态性是 RA 患者流产发生的危险因素。