High Prevalence of Anti-Protein Z and Anti-Protein S Antibodies in Patients with Other Serological Markers for Antiphospholipid Antibodies.
Authors: Ku De-Hui W. , Arkel Yale S. , Lam Xuan , Patel Paresh 
Published: October 2019

Anti-protein Z (aPZ) and protein S (aPS) antibodies have been reported to be associated with adverse pregnancy outcome and thrombosis. We have studied the prevalence of aPZ and aPS antibodies in 63 patients who were referred to our laboratory for antiphospholipid antibody (APA) and lupus inhibitor (LI) evaluation, and 46 normal controls. We considered patients who have increased levels of anticardiolipin (ACL), anti-ß2 glycoprotein I (aB2GPI), or antiphosphatidyl-serine antibodies (aPSer) as APA positive. We define LI positive as patients with prolonged LI sensitive PTT (PTT-LA), and positive for any one of the confirmatory tests (Hexagonal phase assay, platelet neutralization procedure, and diluted Russel Viper Venom Time Ratio). 27 of the 63 patients have APA, 24 of the 63 patients have LI, and 12 of the 63 patients have both APA and LI. Table 1 shows the means and standard deviation (SD) of aPS and aPZ levels of the 63 patients compared to the 46 normal controls. The means aPZ IgM for the total 63 patients group and the 27 patients with APA alone are statistically significantly greater than the control group (p<0.05). We considered aPZ and aPS levels greater than the normal control mean plus 2 SD as positive (aPZ IgG>2.32, IgM>2.95, aPS IgG>3.18, IgM>5.8). Of the 63 patients, 7 (11%) are positive for aPZ IgG, 22 (35%) positive for aPZ IgM, 4 (6%) positive for aPS IgG, and 4 (6%) positive for aPS IgM. In the aPZ, IgG and IgM, positive patients (N=28), 9 (32%) are LI only, 16(57%) are APA only, and 3 (11%) have both LI and APA. Of the 16 APA only, 13 have ACL, 11 have aPSer, and 8 have aB2GPI. For the aPS positive group, 4 positive IgG patients have APA only, and 4 positive IgM patients have LI only. We also have three additional patients other than the 63 patient, who have increased anti-prothrombin antibodies present. These three patients have high aPS IgM antibody (mean 4.50 +/− 3.16). In conclusion, we have found that aPZ IgM antibody are higher in the patients with serological markers for APA and LI compared to our normal controls. We also found that a substantial minority of our patients have increase aPZ (46%) and aPS (13%) antibodies. Since these antibodies have been reported to be associated with thrombosis and adverse pregnancy outcome they may have prognostic implications in those patients with serological markers for APA and LI. We also noticed that high percentage of our aPZ and aPS positive patients have LI. Our data would suggest the inclusion of these antibodies in the evaluation for immune related prothrombotic states and adverse pregnancy outcome. However, larger population study with detailed clinical information and patient outcomes are needed to make appropriated recommendations as to the efficacy for this type of laboratory testing.

Mean aPS and aPZ levels of the 63 patients and 46 controls CTR (N=46) All patients (N=66) APA only (N=30) LI only (N=24) APA + LI (N=12) * vs CTR P<0.05 aPZ IgG 0.50 +/− 0.91 1.01 +/− 2.28 0.92 +/− 1.08 1.20 +/− 3.52 0.84 +/− 0.58 aPZ IgM 0.99 +/− 0.98 2.83 +/− 2.96* 3.07 +/− 2.0* 2.21 +/− 3.66 3.52 +/− 3.24* aPS IgG 0.64 +/− 1.27 0.84 +/− 1.08 1.22 +/− 1.47 0.35 +/− 0.29 0.98 +/− 0.6 aPS IgM 2.02 +/− 1.89 2.51 +/− 3.52 2.22 +/− 1.30 2.93 +/− 5.45 2.30 +/− 1.77