Paper of the week: Lack of Humoral Immunity Against Glucosaminidase Is Associated with Postoperative Complications in Staphylococcus aureus Osteomyelitis

Paper of the week: Lack of Humoral Immunity Against Glucosaminidase Is Associated with Postoperative Complications in Staphylococcus aureus Osteomyelitis

ICM Philly December 1, 2020

Stephen L Kates, John R Owen, Christopher A Beck, Chao Xie, Gowrishankar Muthukrishnan, John L Daiss, Edward M Schwarz.

 The Journal of Bone and Joint Surgery November 4, 2020; 102 (21): 1842doi: 10.2106/JBJS.20.00029. PMID: 32858560.

Summary by: Emanuele Chisari

Infection prevention is the most cost-effective solution to reduce the socioeconomic burden associated with infections. Even though musculoskeletal infections are caused by a multitude of organisms, including bacteria, fungi, and viruses [1-4], Staphylococcus aureus is widely recognized as the most prevalent pathogen involved. As such, many active and passive immunization solutions to prevent S. aureus infection have been developed by scientists and surgeons. Although these solutions have incorporated multiple antigenic targets, technologies, and methodologies, all candidates tested to-date failed to show any benefit in preclinical and clinical studies and were also associated with unfavorable patient outcomes [5-6]. Despite these unsuccessful attempts, the development of effective immunotherapies against S. aureus remains among the highest priorities in orthopaedics, according to the International Consensus Meeting group [7].

In the observational study by Kates et al. [8], S. aureus osteomyelitis patients with high (>10 ng/mL) serum anti- Glucosaminidase (Gmd) antibodies at baseline (before infection treatment) were almost 3 times more likely to control their infection at 1 year. Moreover, there was a 60% reduction in adverse events for every tenfold increase in anti-Gmd antibodies. Kates et al. have previously individuated Gmd through an antigen discovery screen and showed it to be present in the serum of infected patients. Following this exciting line of research, the authors show that passive immunization to Gmd may be associated with better outcomes in infected patients [9-14].

Although the study’s observational design presents limitations that are well acknowledged by the authors, these results are promising for the future of passive immunization in musculoskeletal infections. Further studies are needed to confirm or correct the threshold suggested by the authors in a larger cohort, investigate if anti-Gmd antibodies exist in the periarticular tissues of infected patients, and demonstrate clinical benefit via interventional studies. If anti-Gmd monoclonal antibodies are shown to be protective through further study, Gmd-targeted immunotherapy can be a crucial solution to boost the immune systems of vulnerable patient populations, and eventually, all individuals undergoing high-risk procedures.

References:

  1. Malhas, A. M., Lawton, R., Reidy, M., Nathwani, D. & Clift, B. A. Causative organisms in revision total hip & knee arthroplasty for infection: Increasing multi-antibiotic resistance in coagulase-negative Staphylococcus and the implications for antibiotic prophylaxis ScienceDirect. (2015) doi:10.1016/j.surge.2014.04.002.
  2. Aggarwal, V. K. et al. Organism profile in periprosthetic joint infection: pathogens differ at two arthroplasty infection referral centers in Europe and in the United States. J. Knee Surg. 27, 399–406 (2014).
  3. Russell, C. D., Ramaesh, R., Kalima, P., Murray, A. & Gaston, M. S. Microbiological characteristics of acute osteoarticular infections in Children. J. Med. Microbiol. 64, 446–453 (2015).
  4. Bariteau, J. T. et al. Fungal osteomyelitis and septic arthritis. J. Am. Acad. Orthop. Surg. 22, 390–401 (2014).
  5. Miller, L. S., Fowler, V. G., Shukla, S. K., Rose, W. E. & Proctor, R. A. Development of a vaccine against Staphylococcus aureus invasive infections: Evidence based on human immunity, genetics and bacterial evasion mechanisms. FEMS Microbiology Reviews vol. 44 123–153 (2019).
  6. Fowler, V. G. & Proctor, R. A. Where does a Staphylococcus aureus vaccine stand? Clinical Microbiology and Infection vol. 20 66–75 (2014).
  7. Schwarz, E. M. et al. 2018 International Consensus Meeting on Musculoskeletal Infection: Research Priorities from the General Assembly Questions. Journal of Orthopaedic Research vol. 37 997–1006 (John Wiley and Sons Inc., 2019).
  8. Kates, S. L. et al. Lack of Humoral Immunity Against Glucosaminidase Is Associated with Postoperative Complications in Staphylococcus aureus Osteomyelitis. J. Bone Jt. Surg. 102, 1842–1848 (2020).
  9. Gedbjerg, N. et al. Anti-glucosaminidase IgG in sera as a biomarker of host immunity against staphylococcus aureus in orthopaedic surgery patients. J. Bone Jt. Surg. – Ser. A 95, (2013).
  10. Varrone, J. J. et al. Passive immunization with anti-glucosaminidase monoclonal antibodies protects mice from implant-associated osteomyelitis by mediating opsonophagocytosis of Staphylococcus aureus megaclusters. J. Orthop. Res. 32, 1389–1396 (2014).
  11. Varrone, J. J., Li, D., Daiss, J. L. & Schwarz, E. M. Anti-glucosaminidase monoclonal antibodies as a passive immunization for methicillin-resistant Staphylococcus aureus (MRSA) orthopedic infections. IBMS Bonekey 8, 187–194 (2011).
  12. Oh, I. et al. Tracking anti-Staphylococcus aureus antibodies produced in vivo and ex vivo during foot salvage therapy for diabetic foot infections reveals prognostic insights and evidence of diversified humoral immunity. Infect. Immun. 86, (2018).
  13. Nishitani, K. et al. A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis. Clin. Orthop. Relat. Res. 473, 2735–2749 (2015).
  14. Brady, R. A. et al. Resolution of Staphylococcus aureus biofilm infection using vaccination and antibiotic treatment. Infect. Immun. 79, 1797–1803 (2011).
%d bloggers like this: