Testing for the antiphospholipid syndrome: importance of IgA anti-beta 2-glycoprotein I.
BACKGROUND
Testing for the antiphospholipid syndrome (APS) using anticardiolipin antibodies (aCL) has been problematic. Titers may fluctuate or even become negative. Anti-beta 2-glycoprotein I assays (abeta2-GPI) may be more reliable for diagnosis.


METHODS
In a prospective, blinded study over a nine-month period we retested all patients seen for routine follow-up visits in our clinic who had previously been evaluated for aCL-associated illnesses. Patients were stratified into two groups: group A-patients previously positive for aCL; group B-patients previously negative for aCL. Both groups were further classified according to disease severity. Patients were retested for both aCL and abeta2-GPI (isotypes G, M, A for each) using uniform testing standards.


RESULTS
118 patients with previously positive aCL (group A) were retested. Repeat aCL were positive in 52/118 (44%), abeta2-GPI positive in 69/118 (58%) and 82/118 (69.5%) were positive for one or both assays. In patients with serious organ damage (92% with documented APS), 48.6% were aCL positive, 64% positive for abeta2-GPI, and 75.7% were positive for one or both assays. When only one assay was positive, abeta2-GPI was most frequent (P=0.0096). Overall, IgA abeta2-GPI was the most frequent isotype found (60.9%). On retesting of 73 aCL-negative patients (group B), 9/73 (12%) were aCL positive, 27/73 (36%) were abeta2-GPI positive, with 24/73 (32.9%) having isolated abeta2-GPI. Of those positive for abeta2-GPI, IgA abeta2-GPI was present in 74. 1%. Many of these patients had documented APS.


CONCLUSIONS
Based on our data, abeta2-GPI assays are superior to aCL assays for diagnosis of APS. The combined use of both assays enhance positive testing results in up to 75% of patients with APS at any stage of illness. ACL negative patients suspected of having APS should be retested for both abeta2-GPI and aCL. IgA abeta2-GPI appears to be the most important isotype detected.
Greco
T P
TP
Section of Rheumatology, Yale University School of Medicine, New Haven, CT, USA.
Amos
M D
MD
Conti-Kelly
A M
AM
Naranjo
J D
JD
Ijdo
J W
JW
D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000032:analysis; D000925:Anticoagulants / Q000032:analysis*; D016736:Antiphospholipid Syndrome / Q000175:diagnosis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis*; D007132:Immunoglobulin Isotypes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D000925:Anticoagulants; D006023:Glycoproteins; D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D053482:beta 2-Glycoprotein I