Immunoreactivity and avidity of IgG anti-β2-glycoprotein I antibodies from patients with autoimmune diseases to different peptide clusters of β2-glycoprotein I.
The pathogenicity of antibodies against β2-glycoprotein I (anti-β2GPI) depends on multiple factors such as subclass type, epitope binding and avidity. Due to their large heterogeneity, their impact on antiphospholipid syndrome (APS) onset is still not fully clarified. We studied the binding characteristics of IgG anti-β2GPI with known avidity from sera of 201 autoimmune patients (87 with APS, 67 with APS associated with systemic lupus erythematosus (SLE), 47 with only SLE) to six β2GPI peptides corresponding to amino acid clusters on domains I-II, II, III and III-IV by indirect ELISA and evaluated their association with clinical features of APS. Peptides A (LKTPRV; domain I-II), B (KDKATF; domain IV) and C (TLRVYK; domain III) were derived from a hexapeptide phage display library previously shown to react with pathogenic monoclonal anti-β2GPI. Peptides D (NGPANSK; domain III), E (YNPLWFV; domain II) and F (KMDGNHP; domain III-IV) represent surface amino acid clusters on β2GPI. The percentage of patients positive for peptides were observed as follows: 30.3% for peptide D, 28.90% for B, 25.9% for C, 24.9% for E, 24.4% for F and 10.0% for A. The anti-peptide antibodies in studied serum samples were predominantly of heterogeneous avidity, followed by law avidity anti-peptide antibodies, whereas only a few were of high avidity. Positive and negative correlations were found between several anti-peptide antibodies and the rate of thrombosis. Our results indicated diverse reactivity of IgG anti-β2GPI to different epitopes on β2GPI. Classification of IgG anti-β2GPI into subgroups regarding epitope specificity and avidity could represent an additional tool in understanding their pathogenicity in APS.
Lek Pharmaceuticals d.d., Sandoz Biopharmaceuticals Mengeš, Kolodvorska 27, 1234, Menges, Slovenia.
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A
Artenjak
I
I
Locatelli
H
H
Brelih
D M
DM
Simonič
Z
Z
Ulcova-Gallova
J
J
Swadzba
J
J
Musial
T
T
Iwaniec
L
L
Stojanovich
F
F
Conti
G
G
Valesini
T
T
Avčin
J W
JW
Cohen Tervaert
Y
Y
Shoenfeld
M
M
Blank
A
A
Ambrožič
S
S
Sodin-Semrl
B
B
Božič
S
S
Čučnik
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000915:Antibody Affinity / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D055815:Young Adult; D053482:beta 2-Glycoprotein I / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D007074:Immunoglobulin G; D010455:Peptides; D053482:beta 2-Glycoprotein I