Vazirpanah Nadia, Verhagen Fleurieke H, Rothova Anna, Missotten Tom O A R, van Velthoven Mirjam, Den Hollander Anneke I, Hoyng Carel B, Radstake Timothy R D J, Broen Jasper C A, Kuiper Jonas J W
Laboratory of Translational Immunology, department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, The Netherlands.
PLoS One. 2017 May 1;12(5):e0176175. doi: 10.1371/journal.pone.0176175. eCollection 2017.
Birdshot Uveitis (BU) is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes.
To study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL) in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls.
Although LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL) = 4.87 (= 74131 base pair) compared to 4.31 (= 20417 base pair) in unaffected controls (P<0.0001). The cause underpinning the difference in LTL could not be explained by clinical parameters, immune cell-subtype distribution, nor genetic predisposition based upon the computed weighted genetic risk score of genotyped validated variants in TERC, TERT, NAF1, OBFC1 and RTEL1.
These findings suggest that BU is accompanied by significantly longer LTL.
鸟枪弹样脉络膜视网膜炎(BU)是一种典型的慢性炎症性眼病,视力预后较差,是研究慢性炎症的理想模型。BU通常影响50岁左右的患者。这表明它可能是一种与年龄相关的慢性炎症性疾病,与白细胞端粒长度的侵蚀增加有关。
为了详细研究这一问题,我们采用了一种灵敏的标准化定量实时聚合酶链反应,来测定91例基因分型的荷兰BU患者和150例未受影响的荷兰对照者的外周血白细胞端粒长度(LTL)。
尽管BU患者和健康对照者的LTL侵蚀率非常相似,但我们观察到,BU患者的LTL更长,中位数log(LTL)=4.87(=74131碱基对),而未受影响的对照者为4.31(=20417碱基对)(P<0.0001)。基于TERC、TERT、NAF1、OBFC1和RTEL1中基因分型验证变体的计算加权遗传风险评分,LTL差异的潜在原因无法用临床参数、免疫细胞亚型分布或遗传易感性来解释。
这些发现表明,BU患者伴有明显更长的LTL。