The Role of Circulating Soluble CD74 in Acute Lung Injury

Relationship Between Elevated Soluble Cluster of Differentiation 74 (CD74) and Severity of Experimental and Clinical ALI/ARDS.

Efforts to identify circulating factors that predict severity of acute lung injury/acute respiratory distress syndrome（ALI/ARDS） patients is unrevealing. The primary purpose of this study is to verify our hypothesis that soluble CD74 might be a potential novel ALI/ARDS biomarker.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome; Acute Lung Injury

Detailed Description

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a devastating cause of morbidity and mortality characterized by alveolar epithelial and endothelial injury. Despite recent advances in pathogenetic mechanisms and therapy strategies of ALI, efforts to identify circulating factors that predict severity of ALI/ARDS patients have been unrevealing.

CD74 (also known as a major histocompatibility complex (MHC) class II invariant chain) is a type II transmembrane protein, recently found to be the high-affinity receptor of macrophage migration inhibitory factor (MIF). MIF promotes neutrophil accumulation in alveolar space via binding to CD74 expressed on the cell surface. Our previous study， consistent with others, has shown that MIF was highly expressed in acute lung injury (ALI). In addition, we also detected highly CD74 expression in lipopolysaccharide (LPS)-induced ALI mouse model. Recently, a circulating form of CD74 was discovered in autoimmune liver disease. Similarly, we investigated the existence of soluble form of CD74 in serum and bronchoalveolar lavage fluid (BALF) in ALI mouse model and burn or trauma related ALI patients. Based on these finds, we postulated that soluble CD74 might participate in regulating lung inflammation and be a potential novel ALI/ARDS biomarker.

• Study Type: Observational
• Enrollment (Actual): 139

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200433
    • Department of Burn and Trauma Sugery, Changhai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 100 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with and without ARDS were screened from Changhai Hospital. Patients were enrolled consecutively over a 2-year time period (2014-2015). All enrolled patients with ALI met the American-European Consensus Committee criteria.In addition, healthy individuals were recruited from the general population.

Description

Inclusion Criteria:

• Clinical diagnosis of ALI/ARDS
• Informed consent was obtained from either the subjects themselves or from designated surrogates before enrollment in the study.

Exclusion Criteria:

• Patients who have chronic lung disease before enrollment.
• Patients who have severe organ dysfunction, autoimmune diseases and tumor.
• Women who are pregnant or breast-feeding.
• Patients who, in the opinion of the Investigator, have any other medical condition which renders the patient unable to complete the study or which would interfere with optimal participation in the study or produce significant risk to the patient.
• Patients participating in or planning to enroll in another clinical trial during the time of the study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ARDS patients; Eighty-one patients were enrolled consecutively over a two-year time period (2014-2015) and identified as ARDS prospectively according to the Berlin definitions of the European Society of Intensive Care Medicine and American Thoracic Society on ARDS. Exclusion criteria were an age of less than 16 years, pregnancy, chronic obstructive pulmonary disease according to medical history and failure to obtain informed consent.
Healthy volunteers; Fifty-eight healthy volunteers recruited from the general population who had no significant medical history and no medications were categorized as control patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Receiving Mechanical Ventilation		up to 28 days
Fraction of Inspired Oxygen (FiO2)/Partial Arterial Oxygen Pressure (PO2)		up to 28 days
Acute Physiology and Chronic Health Evaluation (APACHE) II Scores	APACHE II scores range from 0 to 71. A higher values represent a worse outcome.	up to 28 days
Serum Soluble Cluster of Differentiations 74 (sCD74)	The concentration of sCD74 was determined using Elx800 (BioTek Instruments, Inc. VT), and normalization was based on concentration-response curves, using CD74 recombinant protein.	Day 1
Serum Soluble Cluster of Differentiations 74 (sCD74)	The concentration of sCD74 was determined using Elx800 (BioTek Instruments, Inc. VT), and normalization was based on concentration-response curves, using CD74 recombinant protein.	Day 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Length of Stay in the ICU	1 year
Length of Hospital Stay	1 year
Days of Unassisted Ventilation	1 year
Death	up to 28 days
TNF-α	Day 3
IL-6	Day 3
MIF	Day 3

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Investigators: Study Director: Zhaofan Xia, MD PhD, Department of Burn Sugery, Changhai Hospital

Publications and helpful links

General Publications

• Wu G, Sun Y, Wang K, Chen Z, Wang X, Chang F, Li T, Feng P, Xia Z. Relationship between elevated soluble CD74 and severity of experimental and clinical ALI/ARDS. Sci Rep. 2016 Jul 22;6:30067. doi: 10.1038/srep30067.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: July 24, 2014
• First Submitted That Met QC Criteria: July 25, 2014
• First Posted (ESTIMATE): July 28, 2014

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2017
• Last Update Submitted That Met QC Criteria: January 2, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: 20131224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO