Identification of a 5-Plex Cytokine Signature that Differentiates Patients with Multiple Systemic Inflammatory Diseases

Levi Hoste; Bram Meertens; Benson Ogunjimi; Vito Sabato; Khadija Guerti; Jeroen van der Hilst; Jeroen Bogie; Rik Joos; Karlien Claes; Veronique Debacker; Fleur Janssen; Simon J Tavernier; Peggy Jacques; Steven Callens; Joke Dehoorne; Filomeen Haerynck

doi:10.1007/s10753-024-02183-3

Identification of a 5-Plex Cytokine Signature that Differentiates Patients with Multiple Systemic Inflammatory Diseases

Inflammation. 2024 Nov 12. doi: 10.1007/s10753-024-02183-3. Online ahead of print.

Authors

Levi Hoste^{1

2}, Bram Meertens^{1

2}, Benson Ogunjimi^{3

4

5

6

7}, Vito Sabato⁸, Khadija Guerti⁹, Jeroen van der Hilst^{10

11}, Jeroen Bogie^{12

13}, Rik Joos^{4

8

14}, Karlien Claes^{1

2}, Veronique Debacker¹, Fleur Janssen¹⁵, Simon J Tavernier^{1

16

17

18}, Peggy Jacques¹⁹, Steven Callens²⁰, Joke Dehoorne¹⁴, Filomeen Haerynck^{21

22}

Affiliations

¹ Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium.
² Department of Internal Medicine and Pediatrics, Division of Pediatric Pulmonology, Infectious Diseases and Inborn Errors of Immunity ,Ghent University Hospital, European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Network (ERN-RITA) Center, Ghent, Belgium.
³ Rheumatology Department, Antwerp Hospital Network, Antwerp, Belgium.
⁴ Division of Pediatric Rheumatology, Antwerp University Hospital, Edegem, Belgium.
⁵ Antwerp Center for Pediatric Rheumatology and Autoinflammatory Diseases, Antwerp, Belgium.
⁶ Division of Pediatric Rheumatology, Brussels University Hospital, Jette, Belgium.
⁷ Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO) ,Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), University of Antwerp, Antwerp, Belgium.
⁸ Department of Immunology, Allergology, and Rheumatology, Antwerp University Hospital, Edegem, Belgium.
⁹ Department of Clinical Chemistry, Antwerp University Hospital, Edegem, Belgium.
¹⁰ Department of Infectious Diseases and Immune Pathology, Jessa General Hospital, Hasselt, Belgium.
¹¹ Limburg Clinical Research Center, Hasselt University, Hasselt, Belgium.
¹² Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
¹³ University MS Centre, Hasselt University, Hasselt, Belgium.
¹⁴ Department of Pediatric Rheumatology, Ghent University Hospital, European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN-RITA) Center, Ghent, Belgium.
¹⁵ Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
¹⁶ Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
¹⁷ Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
¹⁸ Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
¹⁹ Department of Rheumatology, University Hospital Ghent, Ghent, Belgium.
²⁰ Department of General Internal Medicine, Ghent University Hospital, Ghent, Belgium.
²¹ Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium. filomeen.haerynck@uzgent.be.
²² Department of Internal Medicine and Pediatrics, Division of Pediatric Pulmonology, Infectious Diseases and Inborn Errors of Immunity ,Ghent University Hospital, European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Network (ERN-RITA) Center, Ghent, Belgium. filomeen.haerynck@uzgent.be.

PMID: 39528768
DOI: 10.1007/s10753-024-02183-3

Abstract

Patients with non-infectious systemic inflammation may suffer from one of many diseases, including hyperinflammation (HI), autoinflammatory disorders (AID), and systemic autoimmune disease (AI). Despite their clinical overlap, the pathophysiology and patient management differ between these disorders. We aimed to investigate blood biomarkers able to discriminate between patient groups. We included 44 patients with active clinical and/or genetic systemic inflammatory disease (9 HI, 27 AID, 8 systemic AI) and 16 healthy controls. We quantified 55 serum proteins and combined multiple machine learning algorithms to identify five proteins (CCL26, CXCL10, ICAM-1, IL-27, and SAA) that maximally separated patient groups. High ICAM-1 was associated with HI. AID was characterized by an increase in SAA and decrease in CXCL10 levels. A trend for higher CXCL10 and statistically lower SAA was observed in patients with systemic AI. Principal component analysis and unsupervised hierarchical clustering confirmed separation of disease groups. Logistic regression modelling revealed a high statistical significance for HI (P = 0.001), AID, and systemic AI (P < 0.0001). Predictive accuracy was excellent for systemic AI (AUC 0.94) and AID (0.91) and good for HI (0.81). Further research is needed to validate findings in a larger prospective cohort. Results will contribute to a better understanding of the pathophysiology of systemic inflammatory disorders and can improve diagnosis and patient management.

Keywords: Biomarkers; Cytokines; Inflammation.