True anti-anionic phospholipid immunoglobulin M antibodies can exert lupus anticoagulant activity.
True (cofactor-independent) anticardiolipin antibodies (aCL) are thought to lack lupus anticoagulant (LA) activity and pathogenic potential. A serum monoclonal immunoglobulin Mlambda (mIgMlambda) with aCL and LA activities found in a man with a splenicIgMlambda+ B-cell lymphoplasmacytic lymphoma (LPL) without thrombotic events has been characterized. LPL-derived hybridoma clones (designated HY-FRO) producing the serum mIgMlambda were obtained. mIgMlambda secreted by HY-FRO grown in protein-free culture medium, like that purified from serum, (i) showed binding, in a cofactor-free system, to solid-phase CL and phosphatidylserine (PS) and to the membrane of PS-expressing cells (apoptotic cells and activated platelets); (ii) failed to bind neutral phospholipids (PL), beta2Glycoprotein, histone, ssDNA, dsDNA, human IgG and umbilical vein endothelial cells. Absorption with apoptotic cells abolished its binding to anionic plate-bound CL and PS. IgMlambda-FRO used poorly mutated VH and Vlambda region genes, with a pattern that was inconsistent with an antigen-driven selection. Basic amino acids were present in the IgH complementarity determining region 3 (CDR3), which can be important for binding to anionic PL. These findings demonstrate unequivocally that true anti-anionic PL IgM antibodies can exert LA and indicate this anti-PL type does not involve thrombophilia.
Gallart
Teresa
T
Service of Immunology, Hospital Clínic Universitari, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona University School of Medicine, Barcelona, Spain. tgallart@medicina.ub.es
Benito
Carmen
C
Reverter
Joan-Carles
JC
Bosch
Francesc
F
Blay
Maite
M
Tàssies
Dolors
D
Vigorito
Elena
E
Cervera
Ricard
R
Font
Josep
J
Gomis
Ramon
R
Campo
Elias
E
Vives
Jordi
J
D000368:Aged; D000595:Amino Acid Sequence; D017153:Antibodies, Anticardiolipin / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000494:pharmacology*; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D005803:Genes, Immunoglobulin; D006801:Humans; D006825:Hybridomas; D007075:Immunoglobulin M / Q000276:immunology*; D016682:Lupus Coagulation Inhibitor / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D007075:Immunoglobulin M; D016682:Lupus Coagulation Inhibitor; D010718:Phosphatidylserines