Persistent Unresolved Inflammation in the Mecp2-308 Female Mutated Mouse Model of Rett Syndrome.

Rett syndrome (RTT) is a rare neurodevelopmental disorder usually caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2). Several Mecp2 mutant mouse lines have been developed recapitulating part of the clinical features. In particular, Mecp2-308 female heterozygous mice, bearing a truncating mutation, are a validated model of the disease. While recent data suggest a role for inflammation in RTT, little information on the inflammatory status in murine models of the disease is available. Here, we investigated the inflammatory status by proteomic 2-DE/MALDI-ToF/ToF analyses in symptomatic Mecp2-308 female mice. Ten differentially expressed proteins were evidenced in the Mecp2-308 mutated plasma proteome. In particular, 5 positive acute-phase response (APR) proteins increased (i.e., kininogen-1, alpha-fetoprotein, mannose-binding protein C, alpha-1-antitrypsin, and alpha-2-macroglobulin), and 3 negative APR reactants were decreased (i.e., serotransferrin, albumin, and apolipoprotein A1). CD5 antigen-like and vitamin D-binding protein, two proteins strictly related to inflammation, were also changed. These results indicate for the first time a persistent unresolved inflammation of unknown origin in the Mecp2-308 mouse model.

Increased plasma concentrations of antiprothrombin antibodies in women with recurrent spontaneous abortions.

BACKGROUND: Antiphospholipid antibodies are associated with recurrent fetal loss, but the clinical relevance of antiprothrombin (aPT) antibodies remains controversial. This study was designed to evaluate the relationship of plasma concentrations of aPT antibodies (IgG, IgM, and IgA isotypes) and recurrent spontaneous abortion (RSA) not associated with antiphospholipid-antibody syndrome. METHODS: In this retrospective case-control study, we measured plasma aPT antibodies in 100 pregnant women at 8-12 weeks of gestation who had histories of recurrent abortion not associated with antiphospholipid-antibody syndrome. The controls were 200 healthy gestational-age-matched women with uncomplicated gestations. RESULTS: The mean (SD) plasma aPT concentrations were significantly (P <0.001) higher in women with histories of recurrent abortion than in healthy controls [7.97 (0.79) and 2.08 (0.07) kU/L]. Similarly, the concentrations of IgM aPT were significantly (P <0.001) higher in patients than in controls [5.73 (0.85) and 1.83 (0.05) kU/L]. No differences were found for IgA aPT (P = 0.358). CONCLUSIONS: High concentrations of aPT antibodies (IgG and IgM isotypes) are associated with pregnancy loss in women with RSA. We suggest that the antibodies may have a relevant role in the etiology and pathogenesis of the condition.