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The role of blood podoplanin in patients with viral myocarditis
Changhu Liu1, Mingxin Zhu1, Hongmin Yang1
1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract:
Podoplanin (PDPN), a small mucin-like glycoprotein, was recently found to promote the generation of cardiac ectopic lymphoid follicles and anti-heart autoantibodies (AHA) in viral myocarditis (VMC) mice. Herein, we investigated the blood PDPN expression and its potential clinical value in VMC patients. Overall, 40 VMC patients were enrolled among 112 hospitalized patients with suspected myocarditis. Their serum PDPN levels were higher than those in controlled acute myocardial infarction (AMI) patients (n = 40) and healthy individuals (n = 30) (both p < 0.01) and positively correlated with CRP, IL-17, and IL-4 (all p < 0.01). Elevation of serum PDPN discriminated VMC from AMI (OR = 4.061, p < 0.01) and PDPN addition to the basic model (age, CRP, and peak cTNI) increased AUC values (from 0.822 to 0.933, p = 0.04). Additionally, the serum levels of PDPN ligand CCL-21 were also increased and correlated with PDPN (R = 0.59, p < 0.01) in VMC patients, accompanied by AHA production. Moreover, the anti-MHC antibody was closely related to PDPN levels (R = 0.53, p < 0.01), and anti-MHC-positive patients with VMC displayed higher percentages of CD4+IL-17A+PDPN+T cells and CD19+CCR7+B cells (both p < 0.05). Noticeably, VMC patients complicated by ventricular arrhythmias (27.50%) presented with AHA production and higher PDPN levels (p < 0.05). Finally, we screened out and verified that miR-182-5p directly targeted PDPN and negatively regulated its expression (all p < 0.01). These data suggested that blood PDPN might be a novel inflammation-associated biomarker for the early diagnosis of VMC and may contribute to AHA production by binding CCL-21 to recruit Th17 and B cells, which were regulated by miR-182-5p.
Insights
Podoplanin (PDPN) is a potential biomarker for viral myocarditis (VMC), showing elevated levels in patients and correlating with inflammation and autoantibodies. This glycoprotein may aid in early VMC diagnosis and understanding disease mechanisms.
Area of Science:
- Immunology
- Cardiology
- Biochemistry
Background:
- Podoplanin (PDPN) promotes cardiac ectopic lymphoid follicles and autoantibodies in viral myocarditis (VMC) mouse models.
- The role and clinical significance of PDPN in human VMC remain largely unexplored.
Purpose of the Study:
- To investigate serum PDPN expression in VMC patients.
- To assess the clinical value of PDPN as a diagnostic biomarker for VMC.
- To explore the association of PDPN with inflammation, autoantibodies, and specific immune cell populations in VMC.
Main Methods:
- Serum PDPN levels were measured in 40 VMC patients, 40 acute myocardial infarction (AMI) patients, and 30 healthy controls.
- Correlations between PDPN, C-reactive protein (CRP), Interleukin-17 (IL-17), Interleukin-4 (IL-4), CCL-21, and anti-heart autoantibodies (AHA) were analyzed.
- Diagnostic performance of PDPN for VMC was evaluated using logistic regression and receiver operating characteristic (ROC) analysis.
- Flow cytometry was used to analyze immune cell populations (CD4+ T cells, CD19+ B cells) in relation to PDPN and anti-MHC antibodies.
- The regulatory role of miR-182-5p on PDPN expression was investigated.
Main Results:
- Serum PDPN levels were significantly higher in VMC patients compared to AMI patients and healthy individuals (p < 0.01).
- PDPN levels positively correlated with CRP, IL-17, and IL-4 (p < 0.01) and were elevated in VMC patients with ventricular arrhythmias and AHA production (p < 0.05).
- Elevated PDPN effectively discriminated VMC from AMI (OR = 4.061, p < 0.01) and improved diagnostic accuracy when added to a clinical model (AUC increased from 0.822 to 0.933, p = 0.04).
- PDPN correlated with CCL-21 and anti-MHC antibodies (p < 0.01), and higher percentages of CD4+IL-17A+PDPN+ T cells and CD19+CCR7+ B cells were observed in anti-MHC-positive VMC patients (p < 0.05).
- miR-182-5p was identified as a direct negative regulator of PDPN expression (p < 0.01).
Conclusions:
- Serum PDPN is a promising inflammation-associated biomarker for the early diagnosis of VMC.
- PDPN may contribute to AHA production by facilitating the recruitment of Th17 and B cells via CCL-21.
- miR-182-5p plays a regulatory role in PDPN expression, suggesting potential therapeutic targets.
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