Independent association of anti-β2-glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients

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Abstract

Objective. Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti-β2- glycoprotein I (anti-β2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti-β2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients. Methods. Seventy-five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti-β2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models. Results. Positivity for anti-β2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P = 0.017), with the IgA isotype of anti- β2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti-β2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5). Conclusion. Anti-β2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti- β2GPI as a biomarker of vascular disease in SSc should be further explored.

Original languageEnglish (US)
Pages (from-to)2480-2489
Number of pages10
JournalArthritis and Rheumatism
Volume60
Issue number8
DOIs
StatePublished - Aug 2009

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Anticardiolipin Antibodies
Glycoproteins
Odds Ratio
Pulmonary Hypertension
Mortality
Antibodies
Ischemia
Logistic Models
Systemic Scleroderma
Vascular Diseases
Blood Vessels
Biomarkers
Smoking
Demography
Wounds and Injuries
anticentromere antibody

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

@article{c961b02f09e84ce5a514e7973b9de5a5,
title = "Independent association of anti-β2-glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients",
abstract = "Objective. Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti-β2- glycoprotein I (anti-β2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti-β2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients. Methods. Seventy-five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti-β2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models. Results. Positivity for anti-β2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P = 0.017), with the IgA isotype of anti- β2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti-β2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5). Conclusion. Anti-β2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti- β2GPI as a biomarker of vascular disease in SSc should be further explored.",
author = "Francesco Boin and Stefano Franchini and Colantuoni, {Elizabeth Ann} and Antony Rosen and Fredrick Wigley and {Casciola Rosen}, {Livia A}",
year = "2009",
month = "8",
doi = "10.1002/art.24684",
language = "English (US)",
volume = "60",
pages = "2480--2489",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "8",

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TY - JOUR

T1 - Independent association of anti-β2-glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients

AU - Boin, Francesco

AU - Franchini, Stefano

AU - Colantuoni, Elizabeth Ann

AU - Rosen, Antony

AU - Wigley, Fredrick

AU - Casciola Rosen, Livia A

PY - 2009/8

Y1 - 2009/8

N2 - Objective. Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti-β2- glycoprotein I (anti-β2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti-β2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients. Methods. Seventy-five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti-β2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models. Results. Positivity for anti-β2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P = 0.017), with the IgA isotype of anti- β2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti-β2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5). Conclusion. Anti-β2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti- β2GPI as a biomarker of vascular disease in SSc should be further explored.

AB - Objective. Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti-β2- glycoprotein I (anti-β2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti-β2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients. Methods. Seventy-five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti-β2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models. Results. Positivity for anti-β2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P = 0.017), with the IgA isotype of anti- β2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti-β2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5). Conclusion. Anti-β2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti- β2GPI as a biomarker of vascular disease in SSc should be further explored.

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