title: Early appearance of neutralizing immunoglobulin G3 antibodies is associated with chikungunya virus clearance and long-term clinical protection.
abstract: BACKGROUND
  Chikungunya virus (CHIKV) and related arboviruses have been responsible for large epidemic outbreaks with serious economic and social impact. Although infected individuals clear the virus from the blood, some develop debilitating and prolonged arthralgia.
  
  
  METHODS
  We investigated specificity and strength of antibody responses in a longitudinal study on CHIKV-infected patients and analyzed their association with viral load, cytokine profile, and severity.
  
  
  RESULTS
  We found that CHIKV-specific response is dominated by immunoglobulin G3 (IgG3) antibodies. The antibodies were neutralizing, and patients with high viremia rapidly developed high levels of anti-CHIKV antibodies of this specific isotype. Although these patients endured a more severe disease progression during the acute viremic phase, they cleared the virus faster and did not experience persistent arthralgia. However, significant persistent arthralgia was observed in patients with low viremia who developed IgG3 at a later stage.
  
  
  CONCLUSIONS
  Absence of early CHIKV-specific IgG3 may therefore serve as a specific marker of patients with increased risk of disease.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Yiu-Wing
authors.initials: YW
authors.lastname: Kam
authors.forename: Diane
authors.initials: D
authors.lastname: Simarmata
authors.forename: Angela
authors.initials: A
authors.lastname: Chow
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Her
authors.forename: Terk-Shin
authors.initials: TS
authors.lastname: Teng
authors.forename: Edward K S
authors.initials: EK
authors.lastname: Ong
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.forename: Yee-Sin
authors.initials: YS
authors.lastname: Leo
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
mesh_terms: D000328:Adult; D000368:Aged; D018354:Alphavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers; D002646:Chikungunya virus / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G