Cytokine Profiles and suPAR in Spondylodiscitis

Spondylodiscitis is a primary infection of the intervertebral discs with secondary infection of the adjacent end-plates and vertebral bodies. It is relatively rare with an incidence of 2.4:100.000 and three times more common among men. The process of infection, which is commonly creeping, leads to a destruction of the vertebral bodies and production of abscesses, which can cause neurological deficits.

Clinical symptoms, especially in the early stages, are uncommon. Patients suffer from unspecific back pain and fever occurs only in 50% of all cases. Currently, markers used including leucocyte count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are also unspecific.For this reason of that several weeks may elapse between the first signs of symptoms and the final diagnosis of spondylodiscitis. Therefore, the identification of the pathogen is indispensable for an effective antibiotic therapy.

Spinal infections are generally monomicrobial, frequently with a haematogenous source. Therefore, blood cultures can be used for identifying the pathogens. In case of negative blood cultures, the pathogens can be identified by invasive methods such as percutaneous punch biopsy or CT-guided fine needle aspiration. Despite biopsies, the pathogen can only be identified in two out of three patients. Failures of pathogen identification are mainly due to previous systemic antibiotic treatment. As a consequence, diagnosis is often based on medical imaging methods (CT, MRT, PET, radiograph, skeletal scintigraphy). The disadvantage of these methods is that structural changes of the spine must occur to become visible.

Treatment of an advanced spondylodiscitis consists of removal of the necrotic tissue, stabilization of the affected vertebral bodies and concomitant antibiotic therapy. Randomized studies for the duration of antibiotic treatments have not been published as yet. Current recommendations are between 6 to 12 weeks. For evaluating the therapy response only the clinical improvement and the CRP value are used. The mean period of stay in the hospital is about 49 days.

The goal is to establish a non-invasive method which allows discrimination of infectious and non-infectious diseases to improve the diagnosis of spondylodiscitis. For that purpose, blood and tissue samples from patients with spondylodiscitis and erosive osteochondrosis will be collected and analyzed for their cytokine and suPAR concentration. Erosive osteochondrosis is a non-infectious, degenerative disease of the spine with similar surgical treatment. Thus, it is an optimal reference group. Nevertheless, erosive osteochondrosis includes special types, called modic type I-III. Because modic type I is associated with an immune response caused by repeated traumata of the spine this modic type will be excluded from the study.

Cytokines are messengers, which are present in blood and all tissues, regulating the immune response. In this study, the goal is to assess if cytokine profiles and suPAR contribute to the discrimination of infectious and non-infectious spondylodiscitis and if this could be verified by the characterization of the cytokine-producing cells. Furthermore, the investigators want to analyze the therapy response by measuring the cytokine and suPAR profiles.

Routine blood collection will be carried out directly before surgery and also during the stationary hospitalization on day 4 and day 10. Additional blood collection will be done after 6 weeks and 3 months during the follow-up. At each time point serum and plasma will be used for the study to determine the cytokine and suPAR concentration and expression of the cytokine-producing cells. Necrotic tissue, which is removed during the surgery, will be analyzed microbiologically as well as pathologically. Parts of this tissue will also be used for the determination of cytokines. Further blood samples will be collected when a patient appears again in the Department of Orthopaedic Surgery and Traumatology because of treatment and therapy of a re-infection. A minimum of 15 patients per group - control group (erosive osteochondrosis modic type II-III) and spondylodiscitis - will be included in this study. Both groups should be homogeneous in sex and age distribution.

There will be no additional pain or complications for the patients participating in this study. All samples will be collected for a period of about one year and stored at -80°C. Afterwards, the blood and tissue samples will be analyzed for potential marker suPAR via ELISA and cytokines by using a Multiplex Assay. Furthermore, results will be linked to anamnesis to detect potential correlations. Specific correlations can indicate a diagnostic and perhaps a prognostic value of the measured cytokines and suPAR.