The Role of Circulating Soluble CD74 in Acute Lung Injury

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Acute Lung Injury, Acute Respiratory Distress Syndrome

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ARDS patients<br>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<br>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?
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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 | Measure Description | 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 |