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
PY - 2017
Y1 - 2017
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 - Female
KW - Gene Expression
KW - Genetic Predisposition to Disease
KW - Humans
KW - Leukocytes/immunology
KW - Male
KW - Middle Aged
KW - Real-Time Polymerase Chain Reaction
KW - Telomerase/metabolism
KW - Telomere/metabolism
KW - Telomere Homeostasis
KW - Telomere Shortening
KW - Uveitis/genetics
U2 - 10.1371/journal.pone.0176175
DO - 10.1371/journal.pone.0176175
M3 - Article
C2 - 28459868
SN - 1932-6203
VL - 12
SP - e0176175
JO - PLoS ONE
JF - PLoS ONE
IS - 5
ER -