title: Immunopathology of desialylation: human plasma lipoprotein(a) and circulating anti-carbohydrate antibodies form immune complexes that recognize host cells.
abstract: Human plasma lipoprotein(a) [Lp(a)], the dominant lipoprotein in atherosclerotic plaques, contains an apo(a) subunit of variable size linked to the apoB subunit of a low-density lipoprotein (LDL) molecule. Circulating lipoprotein immune complexes (ICs) assayed by ELISA using microplate-coated anti-apo(a) or anti-apoB antibody for capture and peroxidase-labelled anti-human immunoglobulins as probe consisted mostly of Lp(a) despite several-fold excess of LDL over Lp(a) in plasma. Microplate coating of plasma lipoprotein IC and probing with antibodies to apo(a) and apoB also revealed negligible presence of LDL compared to Lp(a). Peanut agglutinin specific to desialylated O-glycans bound significantly more to Lp(a) recovered after urea dissociation of IC than to free Lp(a). Plasma lipoproteins separated by ultracentrifugation and desialylated by neuraminidase formed IC with naturally occurring antibodies in normal plasma. These de novo ICs agglutinated desialylated but not normal human RBC in proportion to the polyagglutinin antibody titre of plasma used, suggesting availability of multiple unoccupied binding sites on the participating antibodies even after IC formation. Agglutination was inhibitable by galactosides and decreased 4-8 fold if precursor lipoprotein was selectively depleted of Lp(a), showing agglutinating ICs were contributed mainly by desialylated Lp(a) and galactose-specific antibodies. IC was 2 fold more agglutinating if lipoproteins used contained smaller rather than larger Lp(a) molecules of the same number. Small size/high plasma concentration Lp(a) phenotype and neuraminidase-releasing diseases including diabetes are risk factors for vascular disorders. Results suggest a possible route of Lp(a) attachment to vascular cells that offer terminal galactose on surface glycans following desialylation.
authors: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, 695011, India.
authors: P S
authors: PS
authors: Sabarinath
authors: P S
authors: PS
authors: Appukuttan
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D000936:Antigen-Antibody Complex / Q000097:blood*; D001055:Apolipoproteins B / Q000097:blood; D001665:Binding Sites; D002241:Carbohydrates / Q000276:immunology*; D004912:Erythrocytes / Q000378:metabolism; D006386:Hemagglutination Tests; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007536:Isomerism; D017270:Lipoprotein(a) / Q000097:blood*; D019158:N-Acetylneuraminic Acid / Q000276:immunology*; D055815:Young Adult
chemical_list: D000906:Antibodies; D000936:Antigen-Antibody Complex; D001055:Apolipoproteins B; D002241:Carbohydrates; D007075:Immunoglobulin M; D017270:Lipoprotein(a); D019158:N-Acetylneuraminic Acid
references: J Lipid Res. 1997 Nov;38(11):2193-206
references: 9392417
references: Int Urol Nephrol. 2011 Dec;43(4):1143-8
references: 21207147
references: J Lipid Res. 1978 May;19(4):478-88
references: 207802
references: J Lipid Res. 1991 Feb;32(2):317-27
references: 1829751
references: Chem Phys Lipids. 1994 Jan;67-68:161-6
references: 8187210
references: Clin Chem. 2007 Apr;53(4):679-85
references: 17303687
references: Circulation. 1993 Apr;87(4):1135-41
references: 8462142
references: J Clin Invest. 1969 Jul;48(7):1280-91
references: 4893685
references: Clin Immunol. 2010 Jan;134(1):55-65
references: 19427818
references: J Clin Invest. 1987 Aug;80(2):458-65
references: 2956279
references: Int J Biol Macromol. 2001 Jun 12;28(5):365-71
references: 11325423
references: Clin Chim Acta. 2003 Jan;327(1-2):115-22
references: 12482626
references: Scand J Immunol. 2014 Apr;79(4):251-9
references: 24517196
references: Am J Hum Genet. 1997 Aug;61(2):402-17
references: 9311746
references: J Immunoassay Immunochem. 2013;34(2):166-79
references: 23537301
references: J Lipid Res. 2005 Jul;46(7):1353-63
references: 15897601
references: J Lipid Res. 2003 Mar;44(3):487-93
references: 12562876
references: J Biol Chem. 1982 Mar 25;257(6):2744-6
references: 7061447
references: J Biol Chem. 1986 Jul 5;261(19):8712-8
references: 2941420
references: J Clin Invest. 1996 Nov 15;98(10):2414-24
references: 8941661
references: Eur J Immunol. 1989 Dec;19(12):2335-9
references: 2606142
references: Cardiol Clin. 2003 Aug;21(3):333-62
references: 14621450
references: J Biol Chem. 1975 Nov 10;250(21):8518-23
references: 811657
references: Circulation. 1999 Sep 14;100(11):1154-60
references: 10484534
references: Br J Exp Pathol. 1983 Aug;64(4):418-24
references: 6193802
references: Glycoconj J. 2014 May;31(4):289-98
references: 24723206
references: Lipids. 2014 Nov;49(11):1101-13
references: 25142165
references: Immunol Invest. 2013;42(4):324-40
references: 23883200
references: Int J Clin Lab Res. 1997;27(1):14-23
references: 9144023
references: J Clin Diagn Res. 2013 Nov;7(11):2435-7
references: 24392365
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: Diabetes Care. 1981 Jan-Feb;4(1):121-33
references: 7009108
references: Glycobiology. 2005 May;15(5):447-62
references: 15616123
references: J Lipid Res. 2012 Dec;53(12):2773-90
references: 22969153
references: J Biol Chem. 2001 Jun 22;276(25):22200-8
references: 11294842
references: J Lipid Res. 1988 Jan;29(1):1-8
references: 2451704