Molecular and genetic characterizations of five pathogenic and two non-pathogenic monoclonal antiphospholipid antibodies.
Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by thrombosis, recurrent fetal loss and thrombocytopenia. Antiphospholipid antibodies, detected by enzyme-linked immunoabsorbent assays (aCL) and/or in vitro blood clotting assays (LAC) are strongly associated with APS. Both the molecular structures used by pathogenic antiphospholipid antibodies and the genetic mechanisms leading to their production are unknown. We describe here the variable region genes of seven IgG antiphospholipid antibodies derived from two APS patients. Of these, five are pathogenic as defined in a mouse model of thrombosis and two are not. Analyses of the expressed variable region genes show no preferential V gene usage. However, similar to anti-DNA antibodies, pathogenic antiphospholipid antibodies contain an increased number of arginine residues in the third complimentarity-determining region (CDR3) of their H chains. The increased accumulation of arginine residues in the V(H) CDR3 may act to enhance antigen binding, promote disease and point to the importance of the H chain in the pathogenic potential of certain antiphospholipid antibodies.
Chukwuocha
Reginald U
RU
Department of Medicine, Division of Rheumatology, University of California, Los Angeles, 32-59 Rehabilitation Center, 1000 Veteran Avenue, Los Angeles, CA 90095-1670, USA. rchukwu@ula.edu
Zhu
Min
M
Cho
Chul Soo
CS
Visvanathan
Sudha
S
Hwang
Kwan K
KK
Rahman
Anisur
A
Chen
Pojen P
PP
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D017152:Antibodies, Antiphospholipid / Q000737:chemistry / Q000235:genetics*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D022801:Complementarity Determining Regions; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data
D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region