2.
Antibodies against Glucosaminidase as a biomarker of protective
immunity against Staphylococcus aureus osteomyelitis
Nina Gedbjerg, John Daiss, Joshua Hunter, Kirill Gromov, Kjeld Søballe,
Edward Schwarz
The Center for Musculoskeletal Research and Department of Orthopedics
University of Rochester, Rochester, New York, USA and Aarhus University
Hospital, Aarhus, Denmark; Codevax Inc, Rochester, New York, USA; The
Center for Musculoskeletal Research, University of Rochester, Rochester, New
York, USA; Department of Orthopedics, Aarhus University Hospital, Aarhus,
Denmark; Department of Orthopedics, Aarhus University Hospital, Aarhus,
Denmark; The Center for Musculoskeletal Research, University of Rochester,
Rochester, New York, USA
Background:
Methicillin-resistant Staphylococcus aureus is now the most
deadly pathogen in the USA. This has raised concerns for the millions of
people who undergo total joint replacement (TJR) surgery each year, 1-2% of
which will contract chronic osteomyelitis. The standard of care is a two-stage
exchange arthroplasty with a failure rate as high as 30-50%. The choice and
timing of treatment should be based on the patient’s immune status, but at the
moment there are no available biomarkers to make this possible. Based on
preclinical studies that have identified glucosaminidase (Gmd) as an immuno-
dominant antigen, we hypothesize that anti-Gmd antibodies are diagnostic of
protective immunity against S. aureus osteomyelitis.
Purpose / Aim of Study:
To evaluate circulating anti-Gmd antibodies in
patient sera as a biomarker of protective immunity against S. aureus
osteomyelitis.
Materials and Methods:
We developed an ELISA and a Gmd enzyme
inhibition assay to quantify the physical and functional titers of anti-Gmd
antibodies in patient sera respectively using approved IRB protocols. These
titers were determined in sera from 20 healthy controls undergoing primary
TJR surgery, and 32 patients infected with S. aureus osteomyelitis following
TJR surgery.
Findings / Results:
The osteomyelitis patient group had significant higher
titers of anti-Gmd antibodies when compared to the control group (physical
titer p<0.02; functional titer p<0.0001). Furthermore, we demonstrated a
significant correlation between physical and functional titers (p<0.0001).
Conclusions:
Protective immunity requires high-titer neutralizing antibodies
against several S. aureus antigens, including Gmd. We showed that anti-Gmd
antibodies have a diagnostic value as a biomarker of immunity against S.
aureus osteomyelitis and this is the first step towards development of a S.
aureus vaccine.
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