Role of Interleukin 18 (IL-18) and Interleukin 18 Binding Protein (IL-18BP) in the Diagnostic Work-up of Systemic Juvenile Idiopathic Arthritis and Autoinflammatory Diseases: Possible Biomarkers in the Differential Diagnosis of Other Febrile Diseases

March 11, 2026 updated by: Angela Miniaci, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Literature data suggest that elevated blood values of IL-18 and IL-18 Binding Protein and alterations in their ratio may be significantly correlated with various autoinflammatory diseases, such as systemic juvenile idiopathic arthritis, recurrent autoinflammatory fevers etc. In this view, the clinical implication of this observational, prospective, single-centre, non-pharmacological study will be the definition of new laboratory markers that may be useful in the early differential diagnosis of certain rare and serious paediatric diseases.

Study Overview

Status

Not yet recruiting

Conditions

Systemic Juvenile Idiopathic Arthritis (sJIA)

Detailed Description

The primary aim of this study is to investigate the role of IL-18 and IL-18 Binding Protein as biomarkers of systemic Juvenile Idiopathic Arthritis and recurrent autoinflammatory fevers, while the secondary one is to investigate the superiority of IL-18 and IL-18 Binding Protein over other cytokines and inflammatory indexes in the differential diagnosis of systemic Juvenile Idiopathic Arthritis and recurrent fevers of an autoinflammatory nature.

The study will enroll patients referred to the Pediatric Rheumatology Outpatient Clinic of the Pediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy, for suspected Juvenile Idiopathic Arthritis or suspected recurrent fever/self-inflammatory disease.

Patients will be enrolled during the acute phase of the disease and, prior to the start of immunosuppressive therapy (i.e. corticosteroids, colchicine, biological drugs), a blood sample will be taken for haematochemical investigations, according to clinical practice, as well as an additional blood sample for the assay of IL-18 and IL-18 Binding Protein.

The following variables will be considered for each patient: demographic data; key clinical features; haemochromocytometric test; liver and kidney function tests; indexes of inflammation and acute phase proteins; inflammatory cytokines panel; serum values of IL-18 and IL-18 Binding Protein.

Study Type

Observational

Enrollment (Estimated)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Angela Miniaci, MD
Phone Number: 00390512144811
Email: angela.miniaci@aosp.bo.it

Study Locations

Italy
- Bologna
  - Bologna, Bologna, Italy, 40138
    - IRCCS Azienda Ospedaliero-Universitaria di Bologna
    - Contact:
      
      Angela Miniaci, MD
      
      Phone Number: 00390512144811
      
      Email: angela.miniaci@aosp.bo.it
    - Principal Investigator:
      
      Angela Miniaci

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child
Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

The study enrolls patients referred to the Pediatric Rheumatology Outpatient Clinic of the Pediatrics Unit, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy, for suspected Juvenile Idiopathic Arthritis or suspected recurrent fever/self-inflammatory disease.

Description

Inclusion Criteria:

Age between 2 years and 18 years;
Being affected by 1 of the following: Juvenile Idiopathic Arthritis; recurrent fever/ autoinflammatory disease; rheumatic disease; severe infectious diseases (sepsis, meningitis, urinary tract infection, lower respiratory tract infection);
Obtaining informed consent from parents/legal guardians of paediatric patients.

Exclusion Criteria:

• Patients in whom the suspicion of rheumatic disease is based on a finding of subclinical carditis or chorea.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum levels of IL-18, and IL-18BP Time Frame: at T0 - T1(3 months) - T2(12 months)	pg/mL	at T0 - T1(3 months) - T2(12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum levels of inflammatory cytokines Time Frame: at T0 - T1(3 months) - T2(12 months)	IL-6; IL-8; TNF alpha; IL-12p70; IL-1 beta; IL-10 (pg/mL)	at T0 - T1(3 months) - T2(12 months)
Serum levels of acute phase proteins Time Frame: at T0 - T1(3 months) - T2(12 months)	C-reactive protein (mg/dL); amyloid A protein (mg/dL); ferritin (ng/dL); transferrin (mg/dL); fibrinogen (mg/dL)	at T0 - T1(3 months) - T2(12 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Investigators

Principal Investigator: Angela Miniaci, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2027

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

December 1, 2024

First Submitted That Met QC Criteria