Circulating Anti-Beta2-glycoprotein Antibodies and Endothelial Dysfunction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01822990
Recruitment Status : Completed
First Posted : April 4, 2013
Last Update Posted : April 4, 2013
Information provided by (Responsible Party):
Joaquin de Haro, M.D., Hospital Universitario Getafe

Brief Summary:

Circulating anti-beta2-glycoprotein antibodies have been associated with coronary artery disease and peripheral arterial disease. This auto-antibodies could activate endothelial cells leading to the expression of leukocyte adhesion molecules and increasing the release of pro-inflammatory cytokines.

On the other hand, endothelial dysfunction of atherosclerotic patients acts as a primary pathogenic event, as it occur before structural changes are evident on angiogram or ultrasound scan. Loss of endothelial normal function causes vasoconstriction, local coagulation alterations and an increase arterial wall proliferation. This situation s been attributed to a reduction in nitric oxide bioactivity, and to an increase oxygen-free radical formation in the context of the pro-inflammatory status found in atherosclerosis.

Hypothesis: Circulating Anti-beta2-glycoprotein I antibodies could be associated with endothelial dysfunction and nitric oxide metabolism disruption en patients with peripheral arterial disease.

Condition or disease
Peripheral Arterial Disease

Study Type : Observational [Patient Registry]
Actual Enrollment : 60 participants
Observational Model: Case Control
Time Perspective: Prospective
Target Follow-Up Duration: 12 Months
Official Title: Influence of Circulating Anti-beta2-glycoprotein I Antibodies on the Endothelial Function and NO Metabolism in Peripheral Arterial Disease Patients.
Study Start Date : February 2011
Actual Primary Completion Date : July 2012
Actual Study Completion Date : July 2012

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U.S. FDA Resources

Atherosclerotic patients
Male patients with intermittent claudication.
Control subjects
healthy male subjects with normal results on vascular examination and no cardiovascular risk factors, who are not in receipt of any pharmacological treatment, matched by age within two years with peripheral arterial disease patients

Primary Outcome Measures :
  1. Circulating anti-beta2-glycoprotein I antibodies [ Time Frame: 12 months ]
    The titer of circulating anti-endothelial cell antibodies directed against beta2-glycoprotein antigens (Circulating ABGPI) could be detected by indirect immunofluorescence using a diagnosis reagent kit and subjects serum.

  2. Flow-mediated arterial dilatation (FMAD) [ Time Frame: 12 months ]
    FMAD is an ultrasound test based on the ability of endothelial cells to detect changes in shear stress and is one of the most effective and reliable indirect methods for estimating endothelial dysfunction. The ultrasound transducer is applied proximal to the antecubital fossa, and a longitudinal image of the brachial artery is obtained. The basal arterial diameter is determined. A blood pressure cuff is then placed distal to the measurement area and inflated to a pressure of 250 mmHg for five minutes. New measurements of the arterial diameter in the final diastolic phase should be obtained, 60 seconds after the cuff is deflated

  3. Nitrite serum levels [ Time Frame: 12 months ]
    Nitrite serum levels reflects the nitric oxide metabolism. Serum nitrite concentration could be measured by colorimetric analysis using the Griess reaction. This is a chemical reaction which uses sulphanilamide and naphthylethylenediamine dihydrochloride under acid conditions (phosphoric acid).The system is capable of detecting nitric oxide in a variety of biological and experimental fluids, like human serum samples.

  4. Highly sensitive C-reactive protein. [ Time Frame: 12 months ]
    Highly sensitive C-reactive protein levels could be measured using a highly sensitive, automated immunoassay with the human serum samples.

Biospecimen Retention:   Samples Without DNA
Serum samples of all the subjects included.

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Cases: Male patients with intermittent claudication due to peripheral arterial disease after haemodynamic confirmation of the disease by Doppler and treadmill exercise testing. No previous history of autoimmune disease.

Controls: Healthy male subjects with normal results on vascular examination and no cardiovascular risk factors, who were not in receipt of any pharmacological treatment, matched by age within two years with PAD patients.


Inclusion Criteria:

  • Male gender
  • Peripheral arterial disease diagnosis
  • Intermittent claudication.
  • Hemodynamic confirmation of the disease through non-invasive vascular studies.

Exclusion Criteria:

  • Autoimmune disease
  • Previous revascularization of the ischemic limb.
  • Ischemic ulcers
  • Previous history of organ transplants.
  • Treatment with immunosuppressors

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01822990

Hospital Universitario de Getafe
Getafe, Madrid, Spain, 28905
Sponsors and Collaborators
Hospital Universitario Getafe
Principal Investigator: Cesar Varela, MD Hospital Universitario de Getafe
Study Director: Joaquin De Haro, MD Hospital Universitario de Getafe
Study Director: Francisco Acin, MD, PhD Hospital Universitario de Getafe

Responsible Party: Joaquin de Haro, M.D., Study director, Hospital Universitario Getafe Identifier: NCT01822990     History of Changes
Other Study ID Numbers: ABGPINO150613
First Posted: April 4, 2013    Key Record Dates
Last Update Posted: April 4, 2013
Last Verified: March 2013

Keywords provided by Joaquin de Haro, M.D., Hospital Universitario Getafe:
Anti-beta2-glycoprotein antibodies
Peripheral arterial disease
Nitric oxide
Endothelial dysfunction

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Beta 2-Glycoprotein I
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antibiotics, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Interferon Inducers
Radiation-Protective Agents
Protective Agents