ABSTRACT
AIM: To investigate the clinical significance of anti-factor XII (FXII) in a large cohort of patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: This study comprised 127 patients with SLE. IgG and IgM anti-FXII were tested by an in-house ELISA. 123 healthy donors comprised the control group. RESULTS: 51 (40%) patients with SLE and 9 (7%) healthy controls were positive for anti-FXII. IgG and IgM anti-FXII were frequently found in patients with thrombosis (28% and 13%, respectively). Levels of IgG and IgM anti-FXII were higher in patients with thrombosis than in the control group (p<0.001 and p=0.005, respectively). Anti-FXII was more frequent in patients with arterial thrombosis (31% vs 4% for IgG and 14% vs 3% for IgM, respectively) and venous thrombosis than in controls (37% vs 4% for IgG). IgG anti-FXII were more frequent in patients with miscarriages and fetal death (35% and 40% vs 4% for IgM). The prevalence of IgM anti-FXII was not different between groups. CONCLUSION: Anti-FXII are frequent in patients with SLE. Their presence is associated with thrombosis and adverse obstetric history, making these antibodies a novel marker for the antiphospholipid syndrome.
Subject(s)
Antiphospholipid Syndrome/diagnosis , Autoantibodies/blood , Factor XII/immunology , Lupus Erythematosus, Systemic/complications , Abortion, Spontaneous/etiology , Abortion, Spontaneous/immunology , Adult , Antiphospholipid Syndrome/etiology , Biomarkers/blood , Enzyme-Linked Immunosorbent Assay/methods , Female , Fetal Death/etiology , Fetal Death/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Lupus Coagulation Inhibitor/blood , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , Pregnancy , Pregnancy Outcome , Thrombosis/etiology , Thrombosis/immunologyABSTRACT
Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients' sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus.
