title: Haptoglobin polymorphism: a key factor in the proatherogenic role of B cells?
abstract: 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.
authors.affiliation: Department of Clinical Chemistry, Ghent University Hospital, De Pintelaan 185, B 9000 Ghent, Belgium. Joris.delanghe@ugent.be
authors.forename: Joris R
authors.initials: JR
authors.lastname: Delanghe
authors.forename: Michel R
authors.initials: MR
authors.lastname: Langlois
authors.forename: Marc L
authors.initials: ML
authors.lastname: De Buyzere
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000473:pathology*; D001323:Autoantibodies / Q000737:chemistry; D001402:B-Lymphocytes / Q000166:cytology*; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood; D018450:Disease Progression; D006242:Haptoglobins / Q000235:genetics*; D006461:Hemolysis / Q000235:genetics; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000097:blood / Q000235:genetics; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001323:Autoantibodies; D015415:Biomarkers; D000098902:CD163 Antigen; D006242:Haptoglobins; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D051918:Sialic Acid Binding Ig-like Lectin 2; C099252:oxidized low density lipoprotein