Diagnostic and Prognostic Utility of IL-6 and MMP-7 in Pediatric Immune Mediated Interstitial Lung Disease

Pediatric interstitial lung disease (ILD) represents a heterogeneous group of rare but potentially severe pulmonary disorders characterized by diffuse parenchymal involvement and impaired gas exchange. Among these, immune-mediated ILD constitutes a significant subgroup, often associated with autoimmune and inflammatory conditions, leading to progressive lung damage and substantial morbidity.

Early diagnosis and accurate prognostication of pediatric ILD remain challenging due to overlapping clinical presentations, nonspecific radiological findings, and the lack of reliable biomarkers. Consequently, there is an increasing need to identify measurable biological indicators that can aid in both diagnosis and prediction of disease progression.

Interleukin-6 (IL-6) is a pro-inflammatory cytokine that plays a central role in immune regulation and has been implicated in various inflammatory and autoimmune disorders. Elevated IL-6 levels have been associated with disease activity and severity in multiple pulmonary conditions. Similarly, matrix metalloproteinase-7 (MMP-7) is involved in extracellular matrix remodeling and has emerged as a promising biomarker in interstitial lung diseases, reflecting ongoing tissue injury and fibrosis.

The combined assessment of IL-6 and MMP-7 may provide valuable insights into both inflammatory activity and fibrotic processes in immune-mediated ILD. This dual role suggests their potential utility not only as diagnostic markers but also as prognostic indicators for disease progression and clinical outcomes.

This study aims to evaluate the diagnostic and prognostic utility of IL-6 and MMP-7 in children with immune-mediated interstitial lung disease, with the goal of improving early detection, risk stratification, and clinical management.

Study Overview

• Status: Not yet recruiting
• Conditions: Pediatric Immune Mediated Interstitial Lung Disease
• Intervention / Treatment: Diagnostic test: IL-6 (interlukin 6); Radiation: High-Resolution Computed Tomography (HRCT):; Other: Pulmonary Function Tests (PFTs)

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: lamiaa k morssi, assistant lecturer; Phone Number: 01028979861; Email: drlamyaakamel@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Group 1: Immune-mediated ILD

Pediatric patients with confirmed interstitial lung disease associated with immune-mediated disorders, including:

• Connective tissue diseases (CTD) such as SLE, juvenile idiopathic arthritis, juvenile dermatomyositis, mixed connective tissue disease, systemic sclerosis
• Vasculitis-associated ILD
• Sarcoidosis-associated ILD
• Autoimmune musculoskeletal disorders with ILD Group 2: Immune-mediated disease without ILD Pediatric patients with immune-mediated diseases (CTD, vasculitis, sarcoidosis, autoimmune musculoskeletal disorders) but without ILD.

This group serves as a comparison to determine whether elevations in IL-6 and MMP-7 are specific to ILD rather than the underlying immune disease itself.

Group 3: Healthy Controls Age- and sex-matched healthy children without immune-mediated disease or lung disease used as a baseline reference for biomarker levels.

Description

Inclusion Criteria:

• Children aged 2-18 years with immune-mediated interstitial lung disease, including:

  • Connective Tissue Disease-associated ILD (CTD-ILD), such as Juvenile Idiopathic Arthritis, according to ILAR Classification, 2019, Systemic Lupus Erythematosus, according to EULAR/ACR Classification, 2023, Juvenile Dermatomyositis, according to EULAR/ACR Classification for Juvenile Idiopathic Inflammatory Myopathies, 2017, Mixed Connective Tissue Disease, according to Kasukawa Criteria, 2019, and Systemic Sclerosis, according to ACR/EULAR Classification, 2013.
  • Pediatric vasculitis, according to EULAR/PRINTO/PReS Pediatric Vasculitis Classification Criteria, 2022 update.
  • Pediatric sarcoidosis, according to WASOG pediatric consensus, 2019
• Children with newly diagnosed or previously diagnosed cases in whom IL-6 and MMP- 7 biomarker levels can be obtained according to standardized procedures.
• Children whose guardians have provided written informed consent, according to institutional ethical guidelines.

Exclusion Criteria:

• • ILD caused by infectious, environmental, drug-induced, or post-injury etiologies, rather than immune-mediated mechanisms, according to ERS/ATS chILD guidelines, 2025.

  • Patients with incomplete diagnostic documentation preventing confirmation according to recognized criteria, as per disease-specific guidelines mentioned above.
  • Children with other chronic lung diseases unrelated to immune-mediated pathology, such as congenital malformations or cystic fibrosis, according to pediatric pulmonology consensus, 2024.
  • Cases in which biomarker samples cannot be obtained or processed reliably, according to laboratory standards for IL-6 and MMP-7 measurement

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pediatric patients with confirmed interstitial lung disease associated with immune-mediated disorder; Pediatric patients with confirmed interstitial lung disease associated with immune-mediated disorders, including: Connective tissue diseases (CTD) such as SLE, juvenile idiopathic arthritis, juvenile dermatomyositis, mixed connective tissue disease, systemic sclerosis; Vasculitis-associated ILD; Sarcoidosis-associated ILD; Autoimmune musculoskeletal disorders with ILD	Diagnostic test: IL-6 (interlukin 6); Interleukin-6 (IL-6): measured using enzyme-linked immunosorbent assay (ELISA) -Matrix Metalloproteinase-7 (MM7): quantified using standardized ELISA kits; Radiation: High-Resolution Computed Tomography (HRCT): High-Resolution Computed Tomography (HRCT): Evaluation of: (ground-glass opacities, fibrosis, reticular patterns, bronchiectasis) Scoring system may be applied to quantify ILD severity; Other: Pulmonary Function Tests (PFTs); Pulmonary Function Tests (PFTs) Spirometry: (FVC, FEV1, FEV1/FVC ratio)
Patients with immune-mediated disease without ILD; Pediatric patients with immune-mediated diseases (CTD, vasculitis, sarcoidosis, autoimmune musculoskeletal disorders) but without ILD. This group serves as a comparison to determine whether elevations in IL-6 and MMP-7 are specific to ILD rather than the underlying immune disease itself.	Diagnostic test: IL-6 (interlukin 6); Interleukin-6 (IL-6): measured using enzyme-linked immunosorbent assay (ELISA) -Matrix Metalloproteinase-7 (MM7): quantified using standardized ELISA kits; Radiation: High-Resolution Computed Tomography (HRCT): High-Resolution Computed Tomography (HRCT): Evaluation of: (ground-glass opacities, fibrosis, reticular patterns, bronchiectasis) Scoring system may be applied to quantify ILD severity
Healthy Controls; Healthy Controls Age- and sex-matched healthy children without immune-mediated disease or lung disease used as a baseline reference for biomarker levels	Diagnostic test: IL-6 (interlukin 6); Interleukin-6 (IL-6): measured using enzyme-linked immunosorbent assay (ELISA) -Matrix Metalloproteinase-7 (MM7): quantified using standardized ELISA kits

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diagnostic and prognostic utility of interleukin-6 (IL-6) and matrix metalloproteinase-7 (MMP-7) in children with immune-mediated interstitial lung disease (ILD)	To evaluate the diagnostic and prognostic utility of interleukin-6 (IL-6) and matrix metalloproteinase-7 (MMP-7) in children with immune-mediated interstitial lung disease (ILD), including connective tissue diseases (CTD), vasculitis, and sarcoidosis.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare IL-6 and MMP-7 levels among the subgroups	To compare IL-6 and MMP-7 levels among the subgroups: CTD-associated ILD Vasculitis-associated ILD Sarcoidosis-associated ILD Healthy pediatric controls	2 years
To correlate IL-6 and MMP-7 levels with clinical severity, pulmonary function tests, and radiological extent of ILD.		2 years
To assess the potential of IL-6 and MMP-7 as non-invasive biomarkers for early detection, disease monitoring, and prognosis in pediatric immune-mediated ILD.		2 years

Collaborators and Investigators

• Sponsor: Sohag University

Publications and helpful links

General Publications

• 5.Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6:a016295.
• 4.Wynn TA. Integrating mechanisms of pulmonary fibrosis. J Exp Med. 2011;208(7):1339-1350
• 3.Fan LL. Pediatric interstitial lung disease: updates and future directions. Pediatr Pulmonol. 2010;45(8):677-683.
• 2.Biederer J, Schoepf UJ, Mirsadraee S, Schick S, Beer M, Semple S, et al. Pediatric interstitial lung disease: a review with emphasis on connective tissue disease-associated ILD. Radiology. 2012;262(2):623-639.
• 1.Deutsch GH, Young LR, Deterding RR, Fan LL, Dell SD, Reynolds AM, et al. Diffuse lung disease in young children: application of a novel classification scheme. Am J Respir Crit Care Med. 2007;176(11):1120-1128

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 23, 2026
• First Submitted That Met QC Criteria: April 23, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pediatric; interstitial lung disease; IL-6; immune mediated; MM-7
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Circulatory and Respiratory Physiological Phenomena; Respiratory Physiological Phenomena
• Other Study ID Numbers: IRB00013006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No