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Cellular aging over 13 years associated with incident antinuclear antibody positivity in the Baltimore Longitudinal Study of Aging.
Journal of Autoimmunity ( IF 7.9 ) Pub Date : 2019-07-11 , DOI: 10.1016/j.jaut.2019.06.006
Helen C S Meier 1 , Christine G Parks 2 , Hans B Liu 3 , Dale P Sandler 2 , Eleanor M Simonsick 4 , Kevin Deane 5 , Nan-Ping Weng 3
Affiliation  

Age-associated increases in antinuclear antibodies (ANA) in the general population are commonly noted but the mechanisms underlying this observation are unclear. This study aims to evaluate whether shorter peripheral blood mononuclear cell (PBMC) telomere length, a marker of more advanced biological age, is associated with ANA positivity prevalence and incidence in middle and older aged autoimmune disease-free individuals from the Baltimore Longitudinal Study of Aging (BLSA). Telomere length was measured by Southern Blot and categorized into tertiles. ANA was measured in a 1:80 and a 1:160 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4). Multiple logistic regression was used to estimate the odds ratios and 95% confidence intervals of ANA positivity comparing the shorter tertiles of telomere length to the longest tertile for two cross-sectional points in time and then longitudinally to assess the association between shorter telomere length and incident ANA positivity. Cross-sectional analyses were adjusted for sex, race and BMI (N = 368 baseline, N = 370 follow-up) and longitudinal analyses were adjusted for sex, race, BMI and time between baseline and follow-up (N = 246). No statistically significant cross-sectional associations were observed at baseline or follow-up. Among those where ANA negative at baseline, individuals with shorter telomeres were more likely to be ANA positive at follow-up, an average 13 years later. Individuals with short telomeres at both time periods were more likely to be ANA positive. Findings suggest that ANA positivity in the general population may be indicative of immune dysfunction resulting from advanced cellular aging processes.

中文翻译:

巴尔的摩纵向衰老研究中,超过13年的细胞衰老与入射的抗核抗体阳性有关。

通常注意到一般人群中与年龄相关的抗核抗体(ANA)升高,但尚不清楚该观察的基础机制。这项研究的目的是评估巴尔的摩纵向延龄研究中较短的外周血单核细胞(PBMC)端粒长度(更高级的生物学年龄)是否与ANA阳性率和中老年无自身免疫性疾病的个体的发病率相关(BLSA)。端粒长度通过Southern印迹法测量并分类为三分位数。使用HEp-2细胞(血清阳性= 3或4)通过免疫荧光法以1:80和1:160的血清稀释度测定ANA。使用多元logistic回归来估计ANA阳性率的比值比和95%置信区间,比较两个横截面时间点上端粒长度的较短三分位数与最长三分位数之间的差异,然后纵向评估端粒长度较短与入射事件之间的关联ANA阳性。调整了针对性别,种族和BMI的横断面分析(N = 368基线,N = 370随访),并针对性别,种族,BMI和基线与随访之间的时间进行了纵向分析(N = 246)。在基线或随访时未观察到统计学上显着的横断面关联。在基线ANA阴性的患者中,端粒较短的个体在随访中平均ANA阳性的可能性更高,平均13年后。在这两个时期,端粒较短的个体更可能是ANA阳性。研究结果表明,普通人群中的ANA阳性可能预示了由先进的细胞衰老过程导致的免疫功能障碍。
更新日期:2019-11-18
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