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Lack of Humoral Immunity Against Glucosaminidase Is Associated with Postoperative Complications in Staphylococcus
Stephen L Kates1, John R Owen1, Christopher A Beck2
1Department of Orthopaedic Surgery, Virginia Commonwealth University, Richmond, Virginia.
Background:
Glucosaminidase (Gmd) is known to be a protective antigen in animal models of Staphylococcus aureus osteomyelitis. We compared the endogenous anti-Gmd antibody levels in sera of patients with culture-confirmed S. aureus bone infections to their sera at 1 year after operative treatment of the infection.
Methods:
A novel global biospecimen registry of 297 patients with deep-wound culture-confirmed S. aureus osteomyelitis was analyzed to assess relationships between baseline anti-Gmd serum titers (via custom Luminex assay), known host risk factors for infection, and 1-year postoperative clinical outcomes (e.g., infection control, inconclusive, refracture, persistent infection, septic nonunion, amputation, and septic death).
Results:
All patients had measurable humoral immunity against some S. aureus antigens, but only 20 patients (6.7%; p < 0.0001) had high levels of anti-Gmd antibodies (>10 ng/mL) in serum at baseline. A subset of 194 patients (65.3%) who completed 1 year of follow-up was divided into groups based on anti-Gmd level: low (<1 ng/mL, 54 patients; 27.8%), intermediate (<10 ng/mL, 122 patients; 62.9%), and high (>10 ng/mL, 18 patients; 9.3%), and infection control rates were 40.7%, 50.0%, and 66.7%, respectively. The incidence of adverse outcomes in these groups was 33.3%, 16.4%, and 11.1%, respectively. Assessing anti-Gmd level as a continuous variable showed a 60% reduction in adverse-event odds (p = 0.04) for every tenfold increase in concentration. No differences in patient demographics, body mass index of >40 kg/m, diabetes status, age of ≥70 years, male sex, Charlson Comorbidity Index of >1, or Cierny-Mader host type were observed between groups, and these risk factors were not associated with adverse events. Patients with low anti-Gmd titer demonstrated a significant 2.68-fold increased odds of adverse outcomes (p = 0.008).
Conclusions:
Deficiency in circulating anti-Gmd antibodies was associated serious adverse outcomes following operative treatment of S. aureus osteomyelitis. At 1 year, high levels of anti-Gmd antibodies were associated with a nearly 3-fold increase in infection-control odds. Additional prospective studies clarifying Gmd immunization for osteomyelitis are needed.
Level Of Evidence:
Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Insights
Low levels of antibodies against glucosaminidase (Gmd) are linked to worse outcomes in Staphylococcus aureus osteomyelitis patients. Higher anti-Gmd antibody levels correlate with better infection control and reduced adverse events after surgery.
Area of Science:
- Immunology
- Infectious Diseases
- Orthopedic Surgery
Background:
- Glucosaminidase (Gmd) is a known protective antigen in animal models of Staphylococcus aureus osteomyelitis.
- Endogenous anti-Gmd antibody levels were compared in patients with S. aureus bone infections before and after treatment.
Purpose of the Study:
- To assess the relationship between baseline anti-Gmd antibody levels and clinical outcomes in patients with S. aureus osteomyelitis.
- To determine if host risk factors influence these outcomes.
Main Methods:
- Analysis of a biospecimen registry of 297 patients with S. aureus osteomyelitis.
- Assessed baseline anti-Gmd serum titers using a custom Luminex assay.
- Correlated antibody levels with 1-year postoperative outcomes, including infection control and adverse events.
Main Results:
- Only 6.7% of patients had high anti-Gmd antibody levels (>10 ng/mL) at baseline.
- Higher anti-Gmd levels were associated with increased infection control rates (66.7% in high vs. 40.7% in low).
- Low anti-Gmd titers significantly increased the odds of adverse outcomes (2.68-fold), while higher levels reduced adverse event odds by 60% per tenfold increase.
Conclusions:
- Deficiency in circulating anti-Gmd antibodies is associated with adverse outcomes in S. aureus osteomyelitis.
- High anti-Gmd antibody levels correlate with improved infection control post-treatment.
- Further research on Gmd immunization for osteomyelitis is warranted.
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