title: Distinct antibody responses of patients with mild and severe leptospirosis determined by whole proteome microarray analysis.
abstract: Leptospirosis is an important zoonotic disease worldwide. Humans usually present a mild non-specific febrile illness, but a proportion of them develop more severe outcomes, such as multi-organ failure, lung hemorrhage and death. Such complications are thought to depend on several factors, including the host immunity. Protective immunity is associated with humoral immune response, but little is known about the immune response mounted during naturally-acquired Leptospira infection.
  
  
  
  Here, we used protein microarray chip to profile the antibody responses of patients with severe and mild leptospirosis against the complete Leptospira interrogans serovar Copenhageni predicted ORFeome. We discovered a limited number of immunodominant antigens, with 36 antigens specific to patients, of which 11 were potential serodiagnostic antigens, identified at acute phase, and 33 were potential subunit vaccine targets, detected after recovery. Moreover, we found distinct antibody profiles in patients with different clinical outcomes: in the severe group, overall IgM responses do not change and IgG responses increase over time, while both IgM and IgG responses remain stable in the mild patient group. Analyses of individual patients' responses showed that >74% of patients in the severe group had significant IgG increases over time compared to 29% of patients in the mild group. Additionally, 90% of IgM responses did not change over time in the mild group, compared to ~51% in the severe group.
  
  
  
  In the present study, we detected antibody profiles associated with disease severity and speculate that patients with mild disease were protected from severe outcomes due to pre-existing antibodies, while patients with severe leptospirosis demonstrated an antibody profile typical of first exposure. Our findings represent a significant advance in the understanding of the humoral immune response to Leptospira infection, and we have identified new targets for the development of subunit vaccines and diagnostic tests.
authors.affiliation: Fiocruz, Bio-Manguinhos, Brazilian Ministry of Health, Rio de Janeiro, RJ, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Lessa-Aquino
authors.affiliation: Fiocruz, Gonçalo Moniz Research Institute, Brazilian Ministry of Health, Salvador, BA, Brazil.|Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United States of America.
authors.forename: Janet C
authors.initials: JC
authors.lastname: Lindow
authors.affiliation: Antigen Discovery Inc, Irvine, CA, United States of America.
authors.forename: Arlo
authors.initials: A
authors.lastname: Randall
authors.affiliation: Fiocruz, Gonçalo Moniz Research Institute, Brazilian Ministry of Health, Salvador, BA, Brazil.|Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United States of America.
authors.forename: Elsio
authors.initials: E
authors.lastname: Wunder
authors.affiliation: Department of Medicine, Division of Infectious Disease, University of California Irvine, Irvine, California, United States of America.
authors.forename: Jozelyn
authors.initials: J
authors.lastname: Pablo
authors.affiliation: Department of Medicine, Division of Infectious Disease, University of California Irvine, Irvine, California, United States of America.
authors.forename: Rie
authors.initials: R
authors.lastname: Nakajima
authors.affiliation: Department of Medicine, Division of Infectious Disease, University of California Irvine, Irvine, California, United States of America.
authors.forename: Algis
authors.initials: A
authors.lastname: Jasinskas
authors.affiliation: Fiocruz, Gonçalo Moniz Research Institute, Brazilian Ministry of Health, Salvador, BA, Brazil.
authors.forename: Jaqueline S
authors.initials: JS
authors.lastname: Cruz
authors.affiliation: Fiocruz, Gonçalo Moniz Research Institute, Brazilian Ministry of Health, Salvador, BA, Brazil.
authors.forename: Alcineia O
authors.initials: AO
authors.lastname: Damião
authors.affiliation: Fiocruz, Gonçalo Moniz Research Institute, Brazilian Ministry of Health, Salvador, BA, Brazil.
authors.forename: Nívison
authors.initials: N
authors.lastname: Nery
authors.affiliation: Institute of Collective Health, Federal University of Bahia, Salvador, BA, Brazil.
authors.forename: Guilherme S
authors.initials: GS
authors.lastname: Ribeiro
authors.affiliation: Fiocruz, Gonçalo Moniz Research Institute, Brazilian Ministry of Health, Salvador, BA, Brazil.|Institute of Collective Health, Federal University of Bahia, Salvador, BA, Brazil.
authors.forename: Federico
authors.initials: F
authors.lastname: Costa
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United States of America.
authors.forename: José E
authors.initials: JE
authors.lastname: Hagan
authors.affiliation: Fiocruz, Gonçalo Moniz Research Institute, Brazilian Ministry of Health, Salvador, BA, Brazil.
authors.forename: Mitermayer Galvão
authors.initials: MG
authors.lastname: Reis
authors.affiliation: Fiocruz, Gonçalo Moniz Research Institute, Brazilian Ministry of Health, Salvador, BA, Brazil.|Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United States of America.
authors.forename: Albert I
authors.initials: AI
authors.lastname: Ko
authors.affiliation: Fiocruz, Bio-Manguinhos, Brazilian Ministry of Health, Rio de Janeiro, RJ, Brazil.
authors.forename: Marco Alberto
authors.initials: MA
authors.lastname: Medeiros
authors.affiliation: Department of Medicine, Division of Infectious Disease, University of California Irvine, Irvine, California, United States of America.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Felgner
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007921:Leptospira interrogans / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D007922:Leptospirosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology; D008297:Male; D040081:Protein Array Analysis; D020543:Proteome / Q000032:analysis* / Q000276:immunology; D012698:Serologic Tests; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020543:Proteome