University of Manitoba College of Medicine, Winnipeg, Manitoba, Canada.
RMD Open. 2019 Apr 29;5(1):e000874. doi: 10.1136/rmdopen-2018-000874. eCollection 2019.
Antibodies to citrullinated peptides (anti-CCP) develop in individuals predisposed to rheumatoid arthritis (RA). Neutrophil extracellular traps are a major source of citrullinated antigens and the immunomodulatory host defence peptide LL-37. Vitamin D regulates LL-37 expression. This study assessed the associations of LL-37 and anti-CCP, vitamin D metabolites and vitamin D receptor (VDR) polymorphisms in early inflammatory arthritis (EIA).
Serum LL-37, 25-hydroxy-vitamin D (25OHvitD) and anti-CCP were measured by ELISA in treatment naïve EIA (n = 181). VDR single nucleotide polymorphisms (Fok1, Bsm1, Apa1, Taq1, Cdx-2) and HLADRB1 shared epitope (SE) alleles were detected by DNA amplification. Associations were tested in multivariable models. Median (25%, 75%) or percentiles are reported.
Participants (70 % female, age 56 [45, 66] years, disease activity score [DAS28ESR3var] 3.7 [2.8, 4.8], 41 % anti-CCP positive, 68 % RA) had low serum 25OHvitD; 20.5 nmol/L (13.9, 29.0). In multivariable models, controlling for age, sex, SE, smoking and vitamin D deficiency, LL37 level (top quartile) associated with anti-CCP seropositivity (OR 22; 95% CI 4 to 104).
Levels of circulating LL-37 are associated with anti-CCP seropositivity. LL37 activity may be one mechanism linking infection and toxin exposure to anti-CCP generation.
抗瓜氨酸化肽抗体（抗-CCP）在易患类风湿关节炎（RA）的个体中产生。中性粒细胞胞外诱捕网是瓜氨酸化抗原和免疫调节宿主防御肽 LL-37 的主要来源。维生素 D 调节 LL-37 的表达。本研究评估了 LL-37 与抗-CCP、维生素 D 代谢物和维生素 D 受体（VDR）多态性在早期炎症性关节炎（EIA）中的相关性。
采用 ELISA 法检测未经治疗的 EIA（n=181）患者血清中 LL-37、25-羟维生素 D（25OHvitD）和抗-CCP 的水平。采用 DNA 扩增法检测 VDR 单核苷酸多态性（Fok1、Bsm1、Apa1、Taq1、Cdx-2）和 HLADRB1 共享表位（SE）等位基因。在多变量模型中检验相关性。报告中位数（25%，75%）或百分位数。
参与者（70%为女性，年龄 56[45,66]岁，疾病活动评分[DAS28ESR3var]3.7[2.8,4.8]，41%抗-CCP 阳性，68%为 RA）血清 25OHvitD 水平较低；20.5nmol/L（13.9,29.0）。在多变量模型中，校正年龄、性别、SE、吸烟和维生素 D 缺乏后，LL37 水平（最高四分位）与抗-CCP 阳性相关（OR 22；95%CI 4 至 104）。
循环 LL-37 水平与抗-CCP 阳性相关。LL37 活性可能是将感染和毒素暴露与抗-CCP 产生联系起来的机制之一。
