TY - JOUR
T1 - Aberrant leukocyte telomere length in Birdshot Uveitis
AU - Vazirpanah, Nadia
AU - Verhagen, Fleurieke H
AU - Rothova, Anna
AU - Missotten, Tom O A R
AU - van Velthoven, Mirjam
AU - Den Hollander, Anneke I
AU - Hoyng, Carel B
AU - Radstake, Timothy R D J
AU - Broen, Jasper C A
AU - Kuiper, Jonas J W
N1 - Publisher Copyright:
© 2017 Vazirpanah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/5
Y1 - 2017/5
N2 - Purpose: 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. Methods: 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. Results: 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. Conclusions: These findings suggest that BU is accompanied by significantly longer LTL.
AB - Purpose: 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. Methods: 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. Results: 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. Conclusions: These findings suggest that BU is accompanied by significantly longer LTL.
KW - Dutch people
KW - INFLAMMATORY DISEASES
KW - T-CELLS
KW - Telomere length
KW - Telomeres
KW - White blood cells
KW - genetic predisposition
KW - uveitis
UR - https://www.scopus.com/pages/publications/85018978005
U2 - 10.1371/journal.pone.0176175
DO - 10.1371/journal.pone.0176175
M3 - Article
C2 - 28459868
SN - 1932-6203
VL - 12
JO - PLoS ONE [E]
JF - PLoS ONE [E]
IS - 5
M1 - e0176175
ER -