Antiphospholipid antibodies and infertility: The importance of anti-phosphatidylserine antibody

Abstract

Antiphosphplipid antibodies (aPL) have been linked to poor reproductive performance for almost 20 years. Although many different types of antibodies may be present in the so-called antiphospholipid syndrome, the majority of the studies have been focused on anti-cardiolipin and lupus anticoagulant antibodies. However, many other antibodies have been described, among which anti-phosphatidylserine (aPS) is known to have adhesive properties essential for placentation. Therefore, previously unidentified patients with aPS+ may be at increased risk, even in the absence of the classical aPL. The aim of this study was to describe the incidence of aPS in patients with poor reproductive history and compare the results with other abnormal immunological findings. 102 patients with history of either repeated IVF failures (group 1) or recurrent miscarriage (group 2) were submitted to a protocol of immunological evaluation. Recurrent miscarriage was defined as antecedent of ≥ 2 spontaneous previous miscarriages and repeated IVF failures was defined as ≥2 previous failed IVF attempts. The patients were submitted to the following immunological evaluation: group 1: anti-nuclear antibody (ANA), anti-phospholipid antibodies—anti-cardiolipin (aCL) and anti-phosphatidylserine (aPS)—anti-thyroid antibodies (anti-tireoglobulin and anti-microsomal) and natural killer (CD3- CD16+ CD56+) cells count; group 2: the above mentioned exams for group 1 plus cross-match for HLA-sharing assessment, homocysteine level and genetic tests for detection of inherited thrombophilias (data not shown). Fisher’s exact test was used for statistical analysis and a p<0.05 was considered significant. Fifty-three patients (52%) had positive anti-phospholipid tests.Thirty-three patients (32.4%) had aCL and 41 patients (40.2%) presented positive aPS. When the 2 groups were compared, we found an equivalent prevalence of positive aCL: 30.6% (19/62) in group 1 and 35% (14/40) in group 2; p=0.67. The prevalence of positive aPS, however, was significantly higher in group 2: 55% (22/40) vs 30.6% (19/62); p=0.022. Also, 36.4% (12/33) of patients with aCL were negative for aPS. Contrarily, 53.7% (22/41) of patients with positive tests for aPS were negative for aCL. When other immunological abnormalities were studied for aPS positive patients (n=41), we found association with high NK cells in 36.6% (15/41), anti-thyroid antibodies in 9.8% (4/41) and ANA in 29.3% (12/41). Positive aPS and aCL were the only abnormal findings in 8.8% (9/102) and 3.9% (4/102) of all patients, respectively. We found a high prevalence of positive aPS in patients with poor reproductive history (40.2%). Our findings of a higher percentage of aPS positive women in group 2 (55% vs 30.6%) strengthens the importance of phosphatidylserine as a trophoblastic constitutive phospholipid. Autoantibodies against PS might therefore impair placentation and lead to miscarriage. It is noteworthy that neither aCL nor aPS shall be performed alone, because there is a significant number of patients in whom only one or another will be found. Finally, the significant association with other abnormalities in patients aPS+, especially high activated NK cells count (36.6%) and ANA (29.3%), highlights the need of a global immunological evaluation for patients with poor reproductive history, since different abnormalities may indicate distinct and specific treatments.