title: Subclass-specific antibody responses to human cytomegalovirus in lung transplant recipients and their association with constant heavy immunoglobulin G chain polymorphism and virus replication.
abstract: BACKGROUND
  Human cytomegalovirus (HCMV) causes severe infections in transplant recipients. The significance of the HCMV-specific antibody (Ab) response in limiting HCMV replication is not clear. Therefore, we analyzed the HCMV-specific subclass Ab profile in lung transplant recipients (LTRs) and its association with the genomic immunoglobulin G (IgG) heavy-chain variants GM3/17 and HCMV DNAemia.
  
  
  METHODS
  We determined HCMV-specific total IgG, IgG1 and IgG3 Ab levels by enzyme-linked immunoassay and HCMV-DNAemia by quantitative polymerase chain reaction during post-transplant follow-up in 57 LTRs and, in 44 of these recipients, the genetic allotype marker 359a/g variants (reflecting GM3/17 allotypes) by genotyping.
  
  
  RESULTS
  In seropositive LTRs there was a significant Ab response to HCMV viremia (p = 0.0005), especially when low HCMV DNA levels were detected (<1,000 copies/ml: p = 0.0012; DNAemia >1,000 copies/ml: p = 0.0516). In particular, IgG3 but not IgG1, increased with viremia (IgG3: p = 0.0004). IgG1 levels were significantly lower in patients with 359 g/g (GM3/3) than in those with 359 a/g (GM3/17) variant (p < 0.0001). Of note, the IgG3 increase with viremia occurred particularly in patients carrying the IgG1 low-level 359 g/g variant (p < 0.0002).
  
  
  CONCLUSIONS
  These data suggest that the HCMV-specific Ab response, and especially the IgG3 subclass response, correlate significantly with HCMV replication after transplantation. The patients' GM 3/17 variant is significantly associated with their HCMV IgG subclass profile.
authors.affiliation: Department of Virology, Medical University Vienna, Vienna, Austria.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Simon
authors.affiliation: Department of Virology, Medical University Vienna, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Weseslindtner
authors.affiliation: Department of Virology, Medical University Vienna, Vienna, Austria.
authors.forename: Irene
authors.initials: I
authors.lastname: Görzer
authors.affiliation: Department of Virology, Medical University Vienna, Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Pollak
authors.affiliation: Division of Thoracic Surgery, Medical University Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Jaksch
authors.affiliation: Division of Thoracic Surgery, Medical University Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.affiliation: Department of Virology, Medical University Vienna, Vienna, Austria. Electronic address: elisabeth.puchhammer@meduniwien.ac.at.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Puchhammer-Stöckl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000145:classification / Q000276:immunology*; D000917:Antibody Formation; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D014779:Virus Replication; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains
keywords: CMV DNAemia; GM allotype; IgG heavy chain; human cytomegalovirus; lung transplantation