Background and Aims

Seronegative Antiphospholipid Syndrome refers to patients with clinical profile suggestive of Antiphospholipid Syndrome (APS) but persistently negative for antiphospolipid antibodies (aPL) included in APS classification criteria: anticardiolipin (ACA), anti-beta2Glycoprotein I (B2GP) (both IgG or IgM), and lupus anticoagulant.

Methods

We recruited 63 patients, from three Spanish hospitals, with small vessel brain lesions (SVBL), MRI and clinical manifestations compatible with APS and negative for aPL included in APS criteria. We also tested a control group of patients with autoimmune diseases. We performed:

1-ELISA assays for B2GP and ACA (IgA); anti-phosphatidylserine/prothrombin (PS/PT), phosphatidylethanolamine, prothrombin (PT) (IgG, IgM), anti-annexin A5 (IgG).

2-Chemiluminiscence assay for antibodies to Domain 1 of B2GP IgG.

Results

We found 13 patients positive for extra-criteria aPL: 2 (3.1%) for B2GP IgA; 4 (6.1%) for PT IgG, 1 of them was low positive; 4 (6.1%) for PT IgM , 2 were low positive for PS/PT IgM (3.1%) and 1 was low positive for PT IgG and PS/PT IgM (1.5%). Only 3 controls were positive: 1 for PS/PT IgM, 1 for PT IgG and 1 for Annexin A5, all of them low positive. Excluding low positive results, we detected 9 patients and 0 controls positive.

Conclusions

The presence of Abs to B2GP (IgA) and to PT (IgG and IgM) allowed us to identify as aPL-positive 13.8% of seronegative SVBL patients presenting MRI and clinical findings compatible with APS. Follow-up of these patients and additional studies will confirm our results.This work was funded by a grant from the Spanish Society of Internal Medicine (ref: SAFSN-SNCpv).