title: Early treatment with fluconazole may abrogate the development of IgG antibodies in coccidioidomycosis.
abstract: BACKGROUND
  We have observed a number of patients who fail to develop coccidioidal complement fixing (CF) antibody (immunoglobulin [IgG]) after the initiation of early antifungal therapy. Although this is the first description of this phenomenon in mycology, a precedent for the abrogation of the immune response has been observed in other conditions, including primary syphilis and primary Lyme disease.
  
  
  METHODS
  We conducted a retrospective case-control study to determine any patient-specific risk factors associated with this observation. Additionally, in vitro analysis of the coccidioidal CF (IgG) antigen (Cts1) was performed after Coccidioides was grown under escalating fluconazole concentrations.
  
  
  RESULTS
  Seventeen patients persistently positive for coccidioidal IgM antibodies without developing an IgG response (cases) were compared with 64 consecutive patients who did develop coccidioidal CF (IgG) antibodies (controls). Early treatment with antifungals (within 2 weeks of symptom onset) was associated with an abrogation of IgG antibody production (P < .001). With immunodiffusion testing, control serum demonstrated a lack of IgG seroreactivity when Coccidioides posadasii grown in the presence of escalating fluconazole doses (0.5-128 μg/mL) was used as the antigen; however, control serum remained seroreactive for the presence of IgM. The coccidioidal IgG antigen (Cts1) was shown to be diminished when cultures were grown in the presence of fluconazole, lending further in vitro plausibility to our findings.
  
  
  CONCLUSIONS
  The abrogation of an IgG response in patients treated early in the course of coccidioidal infection may complicate serodiagnosis and epidemiologic studies, and further study to determine the potential clinical implications should be performed.
authors.affiliation: Department of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California, Davis, California 95616, USA. grthompson@ucdavis.edu
authors.forename: George R
authors.initials: GR
authors.lastname: Thompson
authors.forename: Jennine M
authors.initials: JM
authors.lastname: Lunetta
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Johnson
authors.forename: Sandra
authors.initials: S
authors.lastname: Taylor
authors.forename: Derek
authors.initials: D
authors.lastname: Bays
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Cohen
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Pappagianis
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000328:Adult; D000368:Aged; D000908:Antibodies, Fungal / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D000935:Antifungal Agents / Q000627:therapeutic use*; D000946:Antigens, Fungal / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002688:Chitinases / Q000235:genetics / Q000378:metabolism; D003045:Coccidioides / Q000276:immunology*; D003047:Coccidioidomycosis / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D005779:Immunodiffusion; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000908:Antibodies, Fungal; D000935:Antifungal Agents; D000946:Antigens, Fungal; D005656:Fungal Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015725:Fluconazole; D002688:Chitinases