Prediction of molecular mimicry between antigens from Leishmania sp. and human: Implications for autoimmune response in systemic lupus erythematosus.

Pathogens and humans share an intrinsic relation related to molecular mimicry in their antigens. Interactions between immune system and pathogenic antigens result in a production of antibodies that could protect against infection, but develop autoreactive responses mediated by autoantibodies that react to pathogenic and human antigens because they share epitopes. In this study, a pipeline of bioinformatic tools was used to explore the repertory of autoantigens implicated in the develop of Systemic Lupus Erythematosus and their homologous in Leishmania sp. With this, we screened and selected 33 molecular mimicry candidates. In 17 autoantigens from lupus was possible to perform epitope prediction and was found that, at least one potential cross epitope. Some of autoantigens with molecular mimicry were Aquaporin 4, nuclear autoantigens such as: Ubiquitin-related modifier 1 and Small nuclear ribonucleoprotein Sm. Also, mitochondrial, and ribosomal autoantigens were found to share molecular mimicry with antigens from Leishmania sp. In conclusion, this is the first study that provide evidence of molecular mimicry between antigens from Leishmania sp. and human. Implications for the develop of SLE and clinical manifestation deserve more study.

Therapeutic value and long-term safety of pulsed estrogen therapy.

OBJECTIVES: To demonstrate equivalent efficacy for menopausal symptoms between Aerodiol nasal spray and reference oral estradiol therapy, and to investigate the endometrial safety and tolerability of Aerodiol in the long term. METHODS: The efficacy of Aerodiol 300 microg, once daily, was compared with oral estradiol 2 mg/day in a randomized, double-blind trial. A statistical test of noninferiority was performed on the mean absolute Kupperman index (KI) obtained after 14 and 23 weeks of the two treatments. Long-term safety was assessed in a 1-year open-label study. The initial Aerodiol dose was 300 microg/day, and was adjusted if required. Endometrial biopsies were obtained at inclusion and at the end of the trial and examined independently by two pathologists. RESULTS: In the equivalence trial, the KI improved similarly in the Aerodiol group (n=317) and the oral estradiol group (n=342). Aerodiol was shown statistically to be at least as effective as oral therapy (P<0.001), but the incidences of mastalgia and withdrawal bleeding were significantly lower in the Aerodiol group (P<0.01 and P<0.001, respectively). In the long-term safety trial (n=408), the rate of Aerodiol treatment continuation at 12 months was 85%, and there was no incidence of endometrial hyperplasia or cancer. Aerodiol dose adaptation was performed by 29% of women. CONCLUSIONS: Aerodiol was shown to have equivalent efficacy to reference oral estradiol therapy, but with better gynaecological acceptability. The endometrial safety of Aerodiol was confirmed in the long term, and the ability to adjust the dosage easily was of benefit to a substantial proportion of women.