Antibody profile in patients with mild and severe leptospirosis. Homo sapiens

Leptospirosis is zoonotic disease of global importance, with over a million cases andnearly 60,000 deaths annually. Symptomatic disease presentation ranges from a mildfebrile disease with non-specific symptoms to severe forms, characterized by multi-organ failure, lung hemorrhage, and death. Factors governing severe outcomes remainunclear, but the host immune response likely plays an important role. In the presentstudy, we applied high throughput techniques to identify the antibody profiles ofpatients with severe and mild leptospirosis. We discovered a limited number ofimmunodominant antigens, specific to patients. Surprisingly, we found the antibodyrepertoire varies in patients with different clinical outcomes and hypothesized thatpatients with mild symptoms were protected from severe disease due to pre-existingantibodies, while the profile of patients with severe outcomes was representative of afirst exposure. These findings represent a substantial step forward in the knowledge ofthe humoral immune response to Leptospira infection, and we have identified newtargets for vaccine and diagnostic test development. Overall design: We used protein microarray chip to profile theantibody responses of patients with severe and mild leptospirosis against the completeLeptospira interrogans serovar Copenhageni predicted ORFeome. Serum samplesfrom patients with mild or severe leptospirosis were collected twice: (i) acute sample,collected at patient admittance at the health care unit and (ii) convalescent sample,collected 5-276 days after the first sampling. Controls consisted of (i) 37 sera fromhealthy Leptospira-unexposed (naïve) volunteers from California/US and (ii) 37 serafrom healthy participants enrolled in a cohort study in a high risk urban slumcommunity in Salvador, endemic for leptospirosis.