Immunoglobulin A anti-beta(2)-glycoprotein antibodies in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death

OBJECTIVE: Studies in rheumatologic populations suggest that immunoglobulin A antiphospholipid antibodies are strongly associated with the clinical ma nifestations of antiphospholipid syndrome. However, the association between immunoglobulin A antiphospholipid antibodies and pregnancy loss is uncerta in. We determined whether immunoglobulin A antiphospholipid antibodies, spe cifically anti-beta (2)-glycoprotein I and anticardiolipin, are associated with the obstetric features of antiphospholipid syndrome. STUDY DESIGN: Sera from 4 groups of women were studied: (1) 133 women who e xperienced unexplained recurrent spontaneous abortion, (2) 48 women who exp erienced unexplained fetal death, (3) 145 healthy fertile control subjects, and (4) 67 women with well-characterized antiphospholipid syndrome. Serum immunoglobulin A, immunoglobulin G, and immunoglobulin M anti-beta (2)-glyc oprotein I and anticardiolipin antibodies were determined by enzyme-linked immunoassay. RESULTS: Groups of women who experienced unexplained recurrent spontaneous abortion and unexplained fetal death had a higher proportion of women who h ad positive test results for immunoglobulin A anti-beta (2)-glycoprotein I antibodies than fertile control subjects (P < .01, chi-square test); these subjects also had higher levels of autoantibody (P =.001, Kruskal-Wallis). Women who experienced recurrent spontaneous abortion had a higher proportio n of women with positive test results for immunoglobulin A anticardiolipin antibodies compared to fertile control subjects (P < .05, chi-square test); this group also had higher levels of autoantibody (P =.0065, Kruskal-Walli s test). Linear regression analysis showed significant correlation between anti-beta (2)-glycoprotein I immunoglobulin A and anti-beta (2)-glycoprotei n I immunoglobulin G (R =.609; P.0001) and less correlation between anticar diolipin immunoglobulin A and anticardiolipin immunoglobulin G (R =.093; P =.065). CONCLUSION: Immunoglobulin A anti-beta (2)-glycoprotein I antibodies are mo re common in women who experience unexplained recurrent spontaneous abortio n and unexplained fetal death whose initial test results are negative for l upus anticoagulant and immunoglobulin G anticardiolipin antibodies compared to fertile control subjects. Therefore, these antibodies may identify addi tional women with clinical features of antiphospholipid syndrome who are no t identified through traditional testing. It is unclear whether these antib odies are directly pathogenic, a result of the pregnancy losses, or markers for an underlying, yet uncharacterized autoimmune disorder.