The Mosaic of “Seronegative” Antiphospholipid Syndrome

Abstract

In the clinical practice it is possible to find patients with clinical signs suggestive of antiphospholipid syndrome (APS), who are persistently negative for the laboratory criteria of APS, that is, anti-cardiolipin antibodies (aCL), anti-β 2-GPI antibodies and lupus anticoagulant. Therefore, it was proposed for these cases the term of seronegative APS (SN-APS). In order to detect autoantibodies with different methodological approaches, sera from 24 patients with SN-APS were analysed for anti-phospholipid antibodies using TLC immunostaining, for anti-vimentin/cardiolipin antibodies by enzyme-linked immunosorbent assay (ELISA), and for anti-annexin V and anti-prothrombin antibodies by ELISA and dot blot. Control groups of our study were 25 patients with APS, 18 with systemic lupus erythematosus (SLE), and 32 healthy controls. Results revealed that 13/24 (54.2%) SN-APS sera were positive for aCL (9 of whom were also positive for lysobisphosphatidic acid) by TLC immunostaining, 11/24 (45.8%) for anti-vimentin/cardiolipin antibodies, 3/24 (12.5%) for anti-prothrombin antibodies, and 1/24 (4.2%) for anti-annexin V antibodies. These findings suggest that in sera from patients with SN-APS, antibodies may be detected using “new” antigenic targets (mainly vimentin/cardiolipin) or methodological approaches different from traditional techniques (mainly TLC immunostaining). Thus, SN-APS represents a mosaic, in which antibodies against different antigenic targets may be detected.

Diagnosis and management of the antiphospholipid syndrome

“…27, 28 This is a poorly-defined disorder with an uncertain relationship with APS, and we recommend against its routine use until its pathogenesis is better defined. Some individuals with reported ‘seronegative APS’ have IgA antibodies against aCL or β 2 GPI, 28–32 or APLA specific for phosphatidylethanolamine and other antigens, 33–35 though the frequency of these positive tests compared to normal individuals is uncertain.…”

Detection of IgG anti-Domain I beta2 Glycoprotein I antibodies by chemiluminescence immunoassay in primary antiphospholipid syndrome

“…While primary APS (PAPS) is defined by no evidence of any underlying systemic autoimmune disorder, the secondary APS is associated with other systemic autoimmune diseases, in particular systemic lupus erythematosus. There are, however, subjects who have the typical clinical features of APS but are negative for the laboratory criteria [2,3]. Therefore, these so-called "seronegative" patients cannot be classified as APS patients and their management could be difficult.…”

The clinical performance of a chemiluminescent immunoassay in detecting anti-cardiolipin and anti-β2 glycoprotein I antibodies. A comparison with a homemade ELISA method

“…There are, moreover, subjects who present the typical clinical features consistent with APS classification but are negative for its laboratory criteria [2,3]. These so-called seronegative patients are not classified as APS patients despite the fact that their negative laboratory results may depend in part or entirely on the poor performance of laboratory tests including enzyme-linked immunosorbent assay (ELISA) [2,3], hence the importance of reproducible, adequately precise, sensitive, and specific aPL tests to diagnose and consequently to treat these subjects.…”