Aberrant leukocyte telomere length in Birdshot Uveitis

Nadia Vazirpanah; Fleurieke H Verhagen; Anna Rothova; Tom O A R Missotten; Mirjam van Velthoven; Anneke I Den Hollander; Carel B Hoyng; Timothy R D J Radstake; Jasper C A Broen; Jonas J W Kuiper

doi:10.1371/journal.pone.0176175

Aberrant leukocyte telomere length in Birdshot Uveitis

Nadia Vazirpanah, Fleurieke H Verhagen, Anna Rothova, Tom O A R Missotten, Mirjam van Velthoven, Anneke I Den Hollander, Carel B Hoyng, Timothy R D J Radstake, Jasper C A Broen, Jonas J W Kuiper

Medical retina and Uveitis

Research output: Contribution to journal › Article › Research › peer-review

Abstract

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.

Original language	English
Pages (from-to)	e0176175
Journal	PLoS ONE
Volume	12
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0176175
Publication status	Published - 2017

Keywords

Female
Gene Expression
Genetic Predisposition to Disease
Humans
Leukocytes/immunology
Male
Middle Aged
Real-Time Polymerase Chain Reaction
Telomerase/metabolism
Telomere/metabolism
Telomere Homeostasis
Telomere Shortening
Uveitis/genetics

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title = "Aberrant leukocyte telomere length in Birdshot Uveitis",

abstract = "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.",

keywords = "Female, Gene Expression, Genetic Predisposition to Disease, Humans, Leukocytes/immunology, Male, Middle Aged, Real-Time Polymerase Chain Reaction, Telomerase/metabolism, Telomere/metabolism, Telomere Homeostasis, Telomere Shortening, Uveitis/genetics",

author = "Nadia Vazirpanah and Verhagen, {Fleurieke H} and Anna Rothova and Missotten, {Tom O A R} and {van Velthoven}, Mirjam and {Den Hollander}, {Anneke I} and Hoyng, {Carel B} and Radstake, {Timothy R D J} and Broen, {Jasper C A} and Kuiper, {Jonas J W}",

year = "2017",

doi = "10.1371/journal.pone.0176175",

language = "English",

volume = "12",

pages = "e0176175",

number = "5",

}

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

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VL - 12

SP - e0176175

JO - PLoS ONE

JF - PLoS ONE

IS - 5

ER -

Aberrant leukocyte telomere length in Birdshot Uveitis

Abstract

Keywords

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