Beta2-microglobulin as a biomarker in peripheral arterial disease: proteomic profiling and clinical studies.
BACKGROUND
Peripheral arterial disease (PAD) is common but commonly unrecognized. Improved recognition of PAD is needed. We used high-throughput proteomic profiling to find PAD-associated biomarkers.


RESULTS
Plasma was collected from PAD patients (ankle brachial index of <0.90; n=45) and subjects with risk factors but without PAD (n=43). Plasma was analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to quantify 1619 protein peaks. The peak intensity of a 12-kDa protein was higher in PAD patients. Western blot analyses and immunoaffinity studies confirmed that this protein was beta2-microglobulin (B2M). In a validation study, B2M was measured by ELISA in plasma in age- and gender-matched PAD (n=20) and non-PAD (n=20) subjects. Finally, we studied a larger cohort of subjects (n=237) referred for coronary angiography but without known PAD. Plasma B2M levels were higher in PAD patients than in non-PAD patients with coronary artery disease. Plasma B2M correlated with ankle brachial index and functional capacity. Independent predictors of PAD were diabetes mellitus, age, and the combination of B2M and C-reactive protein level.


CONCLUSIONS
In PAD patients, circulating B2M is elevated and correlates with the severity of disease independent of other risk factors. These findings might provide a needed biomarker for PAD and new insight into its pathophysiology. Further studies in other populations are needed to confirm the utility of measuring B2M in cardiovascular disease risk assessment.
Wilson
Andrew M
AM
Stanford University School of Medicine, Division of Cardiovascular Medicine, 300 Pasteur Dr, Falk Cardiovascular Research Center, Stanford, CA 94305-5406, USA.
Kimura
Eiichiro
E
Harada
Randall K
RK
Nair
Nandini
N
Narasimhan
Balasubramanian
B
Meng
Xiao-Ying
XY
Zhang
Fujun
F
Beck
Kendall R
KR
Olin
Jeffrey W
JW
Fung
Eric T
ET
Cooke
John P
JP
D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood / Q000150:complications; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D048909:Diabetes Complications / Q000097:blood; D005260:Female; D006801:Humans; D007511:Ischemia / Q000097:blood* / Q000209:etiology; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000209:etiology; D011237:Predictive Value of Tests; D040081:Protein Array Analysis; D040901:Proteomics / Q000379:methods*; D015427:Reperfusion Injury / Q000097:blood; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D001613:beta 2-Microglobulin / Q000032:analysis*
D015415:Biomarkers; D001613:beta 2-Microglobulin; D002097:C-Reactive Protein