BackgroundSystemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. Anti-phospholipid antibodies (aPL) are frequently found in SLE patients. The Antiphospholipid syndrome (APS) represents the clinical association between aPL antibodies and a syndrome of hypercoagulability (recurrent thrombosis and miscarriage). Fifty percent of APS is secondary to SLE. Annexin AV (ANV) exhibits anticoagulant properties, but aPL antibodies formed against it interfere with its function and may be involved in development of thrombosis and miscarriage.Aim of the studyThe current study aimed to find out a relation between ANV (1C T) polymorphism, Anti ANV antibodies (Ig M /G) or ANV plasma level and the pathophysiology of SLE, APS and RPL (Recurrent Pregnancy Loss) and to compare the genetic variation of ANV with the protein product and the influence of the presence of antibodies on ANV plasma level.Material and MethodsDetection of ANV (1C T) gene polymorphism by Polymerase Chain reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay and measurement of Anti-ANV antibodies (Ig M/G) and ANV plasma level by Enzyme Linked Immunosorbent Assay (ELISA) in 55 female patients divided into 3 groups (SLE, APS and RPL) and 20 healthy controls of matched age and gender. ResultsAnti ANV IgM antibodies were significantly associated with APS, this was revealed when we compared patients with Primary APS, Secondary APS and RPL secondary to APS to the control group (P value: 0.02, 0.05 and 0.03 respectively). There was significant difference in ANV plasma level when we compared SLE to Primary APS and to Unexplained RPL (P value: 0.04 and 0.02 respectively) and Secondary to Primary APS (P value: 0.01). PCR- RFLP revealed 2 genotypes of ANV gene: CC and CT representing 32/55 (58.2%) and 23/55 (41.8%) respectively, but we did not find TT. CT genotype was significantly associated to SLE related groups; SLE and APS secondary to SLE with P value: 0.01 in both as compared to controls. There was a highly significant correlation between ANV polymorphism and treatment (P value: <0.01). ANV plasma levels were not affected by the presence of ANV polymorphism (P value: 0.49) or Anti ANV IgM/G (P value: 0.07 and 0.91 respectively). Miscarriage was highly correlated to low ANV plasma level with P value: <0.01 and to the presence of Anti ANV IgM with P value: <0.01. No correlations were found between ANV (plasma level, polymorphism or antibodies IgM/G) and thrombosis with P value: 0.10, 0.80, 0.44 and 0.78 respectively.ConclusionOur study suggests the possibility that the Anti ANV IgM may be involved in the occurrence of recurrent miscarriage in patients with APS. The ANV plasma level may contribute to susceptibility (low levels) or the protection (high levels) against herpercoagulability in APS and RPL patients. It may also reflect the severity of SLE. The Anti ANV antibodies and ANV plasma level seem to be relevant for the prediction of occurrence of miscarriage but are not related to thrombosis. The (1CT) mutation of ANV gene may affect the pathophysiology of SLE and APS secondary to SLE. Our results show that ANV plasma levels are not affected by the presence of ANV polymorphism or Anti ANV IgM/G. ANV may be an important tool in diagnosis and also target for treatment.