The BH1 idiotype defines a population of anticardiolipin antibodies closely associated with the antiphospholipid syndrome

Abstract

Background: A human IgM monoclonal anticardiolipin antibody–BH1–has previously been described, which has characteristics typical of antiphospholipid antibodies in the serum of patients with antiphospholipid syndrome (APS). It appears to be idiotypically distinct from other human monoclonal autoantibodies of different or overlapping ligand-binding specificities derived from patients with related conditions.

Aim: To determine whether the idiotype of BH1 is expressed on particular populations of antibodies (antiphospholipid and anti-β₂-glucoprotein I) in the serum of patients with APS and other conditions.

Methods: Sera from patients with APS (9), systemic lupus erythematosus without APS (`uncomplicated SLE'–9), and rheumatoid arthritis (RA–15), and from normal controls (15) were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with cardiolipin, β₂ glycoprotein I (β₂ GPI), and a polyclonal anti-idiotype raised against BH1 (RIdBH1). Absorption experiments were subsequently performed on selected sera using micelles of cardiolipin or phosphatidyl choline.

Results: Eight out of nine patients with APS were positive for binding to RIdBH1 (IgG and/or IgM), while only one patient with uncomplicated SLE and none of the patients with RA or the healthy controls were positive. Although all of the patients with APS were positive for binding to β₂ GPI, there was poor correlation between these results and levels of binding to cardiolipin and RIdBH1. Absorption of sera from patients with APS by cardolipin micelles resulted in a median reduction in IgG anticardiolipin and anti-β₂ GPI activity of 81.6% and 6.3% respectively. For those sera positive for IgG reactivity with RIdBH1 the median reduction in this activity was 79.4%. Antibodies eluted from selected micelles showed activity against cardiolipin, β₂ GPI and RIdBH1. Three anticardiolipin-positive sera from patients with RA were similarly absorbed; however the eluted antibodies failed to bind to RIdBH1. Absorption of all these sera with phosphatidyl choline resulted in no significant reduction in any of these activities.

Conclusions: The BH1 idiotype defines a population of serum antibodies associated with features of APS. The antibody response in this condition, though diverse, may include the expression of a restricted group of variable region genes.

Keywords

antiphospholipid syndrome Hughes' syndrome anticardiolipin antibody anti-β2 glycoprotein I antibody idiotype

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