Special Poster Session 50th International Society for the Study of the Lumbar Spine Annual Meeting 2024

BACTERIAL AND AUTOIMMUNE ENDOTYPES OF MODIC TYPE 1 CHANGE PATIENTS HAVE DISTINCT BLOOD CYTOKINE PROFILES (#SP-10a)

Irina Heggli 1 2 , Tamara Mengis 1 2 , Christoph J. Laux 3 , Nick Herger 1 2 , Danilo Menghini 1 2 , Nadja A Farshad-Amacker 4 , Aaron J. Fields 5 , Mazda Farshad 3 , Oliver Distler 1 2 , Stefan Dudli 1 2
  1. Center of Experimental Rheumatology, University of Zurich, Zurich, Switzerland
  2. Department of Physical Medicine and Rheumatology, Balgrist University Hospital, Balgrist Campus, University of Zurich, Zurich, Switzerland, Zurich
  3. Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich, Switzerland, Zurich
  4. Department of Radiology, Balgrist University Hospital, University of Zurich, Zurich, Switzerland, Zurich
  5. Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, USA, San Francisco

INTRODUCTION:

Modic type 1 changes (MC1) are vertebral bone marrow (BM) lesions commonly found in patients with chronic low back pain (CLBP). Disease-modifying MC1 treatments are not available. Their development is likely hampered by the unknown etiopathogenesis. Recently, a link between intradiscal Cutibacterium acnes (C.acnes)  load with the adjacent BM immune response was shown1. This provided the first evidence for the existence of bacterial (C.acnes-mediated) and autoimmune endotypes in MC1 patients. In this exploratory study, we hypothesized that patients with different MC1 endotypes can be distinguished based on their blood cytokine profiles.

METHODS:

We collected blood and intervertebral discs from CLBP patients with MC1 (n=19) undergoing lumbar spinal fusion. Intradiscal C.acnes genome copies were quantified with 16S qPCR. Blood plasma was collected and concentrations of 20 innate and adaptive immunity cytokines were measured using MesoScale U-Plex Discovery Assays. The cut-off to distinguish between MC1 endotypes has previously been defined as the upper 99% confidence interval limit of control discs (without adjacent MC1), which was found to be 870 C.acnes copies/gram disc1. Hence, we assigned MC1 patients with >870 C.acnes copies/gram disc to the bacterial MC1 endotype, patients with <870 copies to the autoimmune. Blood plasma protein levels were compared between MC1 endotypes with Mann-Whitney-U test and were corrected for multiple comparisons with Bonferroni correction. Correlations between intradiscal C.acnes copies and blood cytokine concentrations were calculated using Spearman's correlation. Area under the receiver operating characteristic curve (AUC) was calculated for each cytokine that correlated significantly with intradiscal C.acnes load using simple logistic regression. A logistic regression model was calculated for the combination of cytokines that correlated significantly with intradiscal C.acnes load.

RESULTS:

Patients with autoimmune MC1 endotypes had a median of 181 [interquartile range (IQR): 22,375] C.acnes copies/gram disc (n=10), patients with bacterial MC1 endotypes 1897 [IQR: 1228,5650] copies (n=9). Interleukin 13 (IL-13), a cytokine found to be elevated in patients with autoimmune diseases, was higher in autoimmune vs. bacterial MC1 endotypes (false discovery rate (FDR)=0.02) (Figure 1). In the bacterial endotype group, IL-13 was only detected in 1 out of 9 patients (11%), whereas it was detected in 8 out of 10 patients (80%) of the autoimmune endotype group. Furthermore, IFN-y (ρ=-0.64, p-value=0.004), IL-12p70 (ρ=-0.54, p-value=0.018), and IL-13 (ρ=-0.71, p-value=0.0006) correlated negatively with intradiscal C.acnes load. IL-13 discriminated best between the two endotypes (AUC=0.89, sensitivity=100%, specificity=80%). In combination with IFN-y and IL-12p70, the discriminatory ability was further increased (AUC=0.92, sensitivity=89%, specificity=80%) (Table 1).

 

DISCUSSION:

Here we found that MC1 patients of different endotypes can be distinguished based on IL-13, IL-12p70, and IFN-y blood cytokine levels. Endotype-specific patient stratification will likely be key for the development of disease-modifying MC1 treatments. The findings of this exploratory study can help to identify endotype-specific biomarkers. The stratification potential of these cytokines needs to be validated in a larger biomarker study. In summary, the results of this exploratory study may have important clinical implications for the identification of endotype-specific biomarkers for MC1 patients.

 

65439700f1cac-Figure+1.png65439700f1cac-Table+1.png

  1. REFERENCES: 1 Heggli I, et al. (2023). AB1394 INTRADISCAL CUTIBACTERIUM ACNES DECIDE ON INNATE AND ADAPTIVE IMMUNE PATHWAYS IN MODIC TYPE 1 CHANGES. Annals of the Rheumatic Diseases 2023;82:1926.