Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients

Katja Lakota, Julia Feichtinger, Blaž Burja, Tadeja Kuret, Polona Žigon, Žiga Rotar, Rok Ješe, Snezna Sodin-Semrl, Saša Čučnik, Gerhard G Thallinger, Matija Tomšič, Alojzija Hočevar

Research output: Chapter in Book/Report/Conference proceedingConference contributionResearchpeer-review

Abstract

Background: Giant Cell Arteritis (GCA) is a systemic vasculitis affecting primarily large and medium sized arteries. Immediate high dose steroid treatment may prevent urgent complications, such as vision loss and cerebrovascular insults1–3. However, there is a clear lack of data on predicting serological markers and their association to clinical complications.

Objectives: To investigate serological parameters that support clinicians in predicting complications in a large, clinically well-characterized set of untreated GCA patients at time of diagnosis.

Methods: The study included 98 GCA patients (67% female) with a median (IQR) age 74.1 (67.3–78.8) years and a median (IQR) symptome duration time of 30 (20–90) days). Healthy blood donors (HDs, n=52, 61.5% female, median (IQR) age of 41.95 (20.4–63.1) years) served as controls. GCA complications studied were visual disturbances (including permanent loss of vision), relapses, peripheral artery involvement and claudication. Levels of 27 serum analytes were measured using Luminex xMAP Technology. Interleukin-6 (IL-6) and serum amyloid A (SAA) levels were tested using ELISA and nephelometry, respectively.

Results: The highest, significantly elevated analytes in GCA vs. HDs were SAA (85-fold > HDs mean values), IL-23 (63-fold) and IL-6 (11-fold). IL-13, α-fetoprotein and MMP-2 were significantly decreased in GCA, while levels of IL-2, IL-17A and TNF-α were unchanged. PCA analysis revealed a signature analyte profile positioning towards the HD cluster. SAA, CRP, haptoglobin, ESR, thrombocyte # and matrix metalloproteinase-1 (MMP-1) all negatively associated with visual disturbances, confirming our previous data. Age showed significant association to permanent visual loss, with older patients being more affected3. SAA, CRP and ESR at presentation were found to be predictive of relapsing disease, while MMP-2 negatively associated with relapse. VCAM-1, α-fetoprotein, MARCO and IL-27 were all negatively associated with peripheral artery involvement. MMP-2 and MARCO showed positive association with claudication, while IL-18 was negatively associated.

Conclusions: In our large study of untreated GCA patients we highlight the importance of using serological acute phase parameters, MMPs and other analytes for predicting complications.

References:

Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med 2003, 349:160–169.

Nesher G: The diagnosis and classification of giant cell arteritis. J Autoimmun 2014, 48–49:73–75.

1Hocevar A et al. Do Early Diagnosis and Glucocorticoid Treatment Decrease the 2Risk of Permanent Visual Loss and Early Relapses in Giant Cell Arteritis: A 3Prospective Longitudinal Study. Medicine (Baltimore) 2016, 95:e3210.

LanguageEnglish
Title of host publicationAnnals of the Rheumatic Diseases
Place of PublicationLondon
PublisherBMJ Publ. Group
Pages219
Volume76
EditionSupplement 2
ISBN (Electronic)1468-2060
ISBN (Print)0003-4967
DOIs
StatusPublished - 14 Jun 2017

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Giant Cell Arteritis
Biomarkers
Serum Amyloid A Protein
Matrix Metalloproteinases
Therapeutics
Arteries
alpha-Fetoproteins
Recurrence
Interleukin-6
Interleukin-27
Interleukin-11
Nephelometry and Turbidimetry
Interleukin-23
Systemic Vasculitis
Baltimore
Matrix Metalloproteinase 1
Passive Cutaneous Anaphylaxis
Interleukin-18
Haptoglobins
Interleukin-13

Fields of Expertise

  • Human- & Biotechnology
  • Information, Communication & Computing

Treatment code (Nähere Zuordnung)

  • Basic - Fundamental (Grundlagenforschung)

Cite this

Lakota, K., Feichtinger, J., Burja, B., Kuret, T., Žigon, P., Rotar, Ž., ... Hočevar, A. (2017). Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients. In Annals of the Rheumatic Diseases (Supplement 2 ed., Vol. 76, pp. 219). London: BMJ Publ. Group. DOI: 10.1136/annrheumdis-2017-eular.3467

Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients. / Lakota, Katja; Feichtinger, Julia; Burja, Blaž; Kuret, Tadeja; Žigon, Polona; Rotar, Žiga; Ješe, Rok; Sodin-Semrl, Snezna; Čučnik, Saša; Thallinger, Gerhard G; Tomšič, Matija; Hočevar, Alojzija.

Annals of the Rheumatic Diseases. Vol. 76 Supplement 2. ed. London : BMJ Publ. Group, 2017. p. 219.

Research output: Chapter in Book/Report/Conference proceedingConference contributionResearchpeer-review

Lakota, K, Feichtinger, J, Burja, B, Kuret, T, Žigon, P, Rotar, Ž, Ješe, R, Sodin-Semrl, S, Čučnik, S, Thallinger, GG, Tomšič, M & Hočevar, A 2017, Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients. in Annals of the Rheumatic Diseases. Supplement 2 edn, vol. 76, BMJ Publ. Group, London, pp. 219. DOI: 10.1136/annrheumdis-2017-eular.3467
Lakota K, Feichtinger J, Burja B, Kuret T, Žigon P, Rotar Ž et al. Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients. In Annals of the Rheumatic Diseases. Supplement 2 ed. Vol. 76. London: BMJ Publ. Group. 2017. p. 219. Available from, DOI: 10.1136/annrheumdis-2017-eular.3467
Lakota, Katja ; Feichtinger, Julia ; Burja, Blaž ; Kuret, Tadeja ; Žigon, Polona ; Rotar, Žiga ; Ješe, Rok ; Sodin-Semrl, Snezna ; Čučnik, Saša ; Thallinger, Gerhard G ; Tomšič, Matija ; Hočevar, Alojzija. / Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients. Annals of the Rheumatic Diseases. Vol. 76 Supplement 2. ed. London : BMJ Publ. Group, 2017. pp. 219
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abstract = "Background: Giant Cell Arteritis (GCA) is a systemic vasculitis affecting primarily large and medium sized arteries. Immediate high dose steroid treatment may prevent urgent complications, such as vision loss and cerebrovascular insults1–3. However, there is a clear lack of data on predicting serological markers and their association to clinical complications. Objectives: To investigate serological parameters that support clinicians in predicting complications in a large, clinically well-characterized set of untreated GCA patients at time of diagnosis. Methods: The study included 98 GCA patients (67{\%} female) with a median (IQR) age 74.1 (67.3–78.8) years and a median (IQR) symptome duration time of 30 (20–90) days). Healthy blood donors (HDs, n=52, 61.5{\%} female, median (IQR) age of 41.95 (20.4–63.1) years) served as controls. GCA complications studied were visual disturbances (including permanent loss of vision), relapses, peripheral artery involvement and claudication. Levels of 27 serum analytes were measured using Luminex xMAP Technology. Interleukin-6 (IL-6) and serum amyloid A (SAA) levels were tested using ELISA and nephelometry, respectively. Results: The highest, significantly elevated analytes in GCA vs. HDs were SAA (85-fold > HDs mean values), IL-23 (63-fold) and IL-6 (11-fold). IL-13, α-fetoprotein and MMP-2 were significantly decreased in GCA, while levels of IL-2, IL-17A and TNF-α were unchanged. PCA analysis revealed a signature analyte profile positioning towards the HD cluster. SAA, CRP, haptoglobin, ESR, thrombocyte # and matrix metalloproteinase-1 (MMP-1) all negatively associated with visual disturbances, confirming our previous data. Age showed significant association to permanent visual loss, with older patients being more affected3. SAA, CRP and ESR at presentation were found to be predictive of relapsing disease, while MMP-2 negatively associated with relapse. VCAM-1, α-fetoprotein, MARCO and IL-27 were all negatively associated with peripheral artery involvement. MMP-2 and MARCO showed positive association with claudication, while IL-18 was negatively associated. Conclusions: In our large study of untreated GCA patients we highlight the importance of using serological acute phase parameters, MMPs and other analytes for predicting complications. References: Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med 2003, 349:160–169. Nesher G: The diagnosis and classification of giant cell arteritis. J Autoimmun 2014, 48–49:73–75. 1Hocevar A et al. Do Early Diagnosis and Glucocorticoid Treatment Decrease the 2Risk of Permanent Visual Loss and Early Relapses in Giant Cell Arteritis: A 3Prospective Longitudinal Study. Medicine (Baltimore) 2016, 95:e3210.",
author = "Katja Lakota and Julia Feichtinger and Blaž Burja and Tadeja Kuret and Polona Žigon and Žiga Rotar and Rok Ješe and Snezna Sodin-Semrl and Saša Čučnik and Thallinger, {Gerhard G} and Matija Tomšič and Alojzija Hočevar",
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T1 - Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients

AU - Lakota,Katja

AU - Feichtinger,Julia

AU - Burja,Blaž

AU - Kuret,Tadeja

AU - Žigon,Polona

AU - Rotar,Žiga

AU - Ješe,Rok

AU - Sodin-Semrl,Snezna

AU - Čučnik,Saša

AU - Thallinger,Gerhard G

AU - Tomšič,Matija

AU - Hočevar,Alojzija

PY - 2017/6/14

Y1 - 2017/6/14

N2 - Background: Giant Cell Arteritis (GCA) is a systemic vasculitis affecting primarily large and medium sized arteries. Immediate high dose steroid treatment may prevent urgent complications, such as vision loss and cerebrovascular insults1–3. However, there is a clear lack of data on predicting serological markers and their association to clinical complications. Objectives: To investigate serological parameters that support clinicians in predicting complications in a large, clinically well-characterized set of untreated GCA patients at time of diagnosis. Methods: The study included 98 GCA patients (67% female) with a median (IQR) age 74.1 (67.3–78.8) years and a median (IQR) symptome duration time of 30 (20–90) days). Healthy blood donors (HDs, n=52, 61.5% female, median (IQR) age of 41.95 (20.4–63.1) years) served as controls. GCA complications studied were visual disturbances (including permanent loss of vision), relapses, peripheral artery involvement and claudication. Levels of 27 serum analytes were measured using Luminex xMAP Technology. Interleukin-6 (IL-6) and serum amyloid A (SAA) levels were tested using ELISA and nephelometry, respectively. Results: The highest, significantly elevated analytes in GCA vs. HDs were SAA (85-fold > HDs mean values), IL-23 (63-fold) and IL-6 (11-fold). IL-13, α-fetoprotein and MMP-2 were significantly decreased in GCA, while levels of IL-2, IL-17A and TNF-α were unchanged. PCA analysis revealed a signature analyte profile positioning towards the HD cluster. SAA, CRP, haptoglobin, ESR, thrombocyte # and matrix metalloproteinase-1 (MMP-1) all negatively associated with visual disturbances, confirming our previous data. Age showed significant association to permanent visual loss, with older patients being more affected3. SAA, CRP and ESR at presentation were found to be predictive of relapsing disease, while MMP-2 negatively associated with relapse. VCAM-1, α-fetoprotein, MARCO and IL-27 were all negatively associated with peripheral artery involvement. MMP-2 and MARCO showed positive association with claudication, while IL-18 was negatively associated. Conclusions: In our large study of untreated GCA patients we highlight the importance of using serological acute phase parameters, MMPs and other analytes for predicting complications. References: Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med 2003, 349:160–169. Nesher G: The diagnosis and classification of giant cell arteritis. J Autoimmun 2014, 48–49:73–75. 1Hocevar A et al. Do Early Diagnosis and Glucocorticoid Treatment Decrease the 2Risk of Permanent Visual Loss and Early Relapses in Giant Cell Arteritis: A 3Prospective Longitudinal Study. Medicine (Baltimore) 2016, 95:e3210.

AB - Background: Giant Cell Arteritis (GCA) is a systemic vasculitis affecting primarily large and medium sized arteries. Immediate high dose steroid treatment may prevent urgent complications, such as vision loss and cerebrovascular insults1–3. However, there is a clear lack of data on predicting serological markers and their association to clinical complications. Objectives: To investigate serological parameters that support clinicians in predicting complications in a large, clinically well-characterized set of untreated GCA patients at time of diagnosis. Methods: The study included 98 GCA patients (67% female) with a median (IQR) age 74.1 (67.3–78.8) years and a median (IQR) symptome duration time of 30 (20–90) days). Healthy blood donors (HDs, n=52, 61.5% female, median (IQR) age of 41.95 (20.4–63.1) years) served as controls. GCA complications studied were visual disturbances (including permanent loss of vision), relapses, peripheral artery involvement and claudication. Levels of 27 serum analytes were measured using Luminex xMAP Technology. Interleukin-6 (IL-6) and serum amyloid A (SAA) levels were tested using ELISA and nephelometry, respectively. Results: The highest, significantly elevated analytes in GCA vs. HDs were SAA (85-fold > HDs mean values), IL-23 (63-fold) and IL-6 (11-fold). IL-13, α-fetoprotein and MMP-2 were significantly decreased in GCA, while levels of IL-2, IL-17A and TNF-α were unchanged. PCA analysis revealed a signature analyte profile positioning towards the HD cluster. SAA, CRP, haptoglobin, ESR, thrombocyte # and matrix metalloproteinase-1 (MMP-1) all negatively associated with visual disturbances, confirming our previous data. Age showed significant association to permanent visual loss, with older patients being more affected3. SAA, CRP and ESR at presentation were found to be predictive of relapsing disease, while MMP-2 negatively associated with relapse. VCAM-1, α-fetoprotein, MARCO and IL-27 were all negatively associated with peripheral artery involvement. MMP-2 and MARCO showed positive association with claudication, while IL-18 was negatively associated. Conclusions: In our large study of untreated GCA patients we highlight the importance of using serological acute phase parameters, MMPs and other analytes for predicting complications. References: Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med 2003, 349:160–169. Nesher G: The diagnosis and classification of giant cell arteritis. J Autoimmun 2014, 48–49:73–75. 1Hocevar A et al. Do Early Diagnosis and Glucocorticoid Treatment Decrease the 2Risk of Permanent Visual Loss and Early Relapses in Giant Cell Arteritis: A 3Prospective Longitudinal Study. Medicine (Baltimore) 2016, 95:e3210.

U2 - 10.1136/annrheumdis-2017-eular.3467

DO - 10.1136/annrheumdis-2017-eular.3467

M3 - Conference contribution

SN - 0003-4967

VL - 76

SP - 219

BT - Annals of the Rheumatic Diseases

PB - BMJ Publ. Group

CY - London

ER -