Haptoglobin polymorphism: A key factor in the proatherogenic role of B cells?

B cells play a role in atherosclerosis. B lymphocytes may reduce the progression of vascular disease. Antibody production against modified auto-antigens is an element in the atheroprotective involvement of B lymphocytes. Paradoxical evidence is emerging from animal studies that suggest a proatherogenic B-cell behaviour independently of autoantibody production. One aspect that has received limited consideration is the role of genetic susceptibility modulated by extracellular matrix proteins. Haptoglobin is a polymorphic glycoprotein that binds to CD22 on B lymphocytes. Hp phenotypes show an important molecular heterogeneity. Hp 2-2 has been linked to an increased susceptibility for atherosclerosis. Haptoglobin and its polymorphism play a role in B-cell migration and function. Hp phenotypes may influence B-T cell dialogue and T cell activation. Haptoglobin is involved in the interplay of lymphocytes, neutrophils, and monocytes. Haptoglobin binds to the CD11b/CD18 receptor and to mast cells. HDL particles can become pro-inflammatory through interactions of Hp-Hb complexes with apolipoprotein A1. Haptoglobin is a chemoattractant to pre-B lymphocytes and monocytes. Beyond the conventional view of haptoglobin as a marker of hemolysis, several findings point towards an immunomodulatory effect of haptoglobin in B-cell mediated progression of atherosclerosis. The balance between proatherogenic and protective immunological properties of the different Hp phenotypes determines if lesions progress or regress. Clinical studies indicate a strong association between the Hp 2-2 phenotype and a more frequent onset of diabetic complications and cardiovascular disease. Findings in animal models (where no haptoglobin polymorphism is present) cannot always be extrapolated to humans. (C) 2011 Elsevier Ireland Ltd. All rights reserved.