mycoplasma pneumoniae (MP) infection, a common cause of community-acquired pneumonia, can trigger extrapulmonary complications affecting various organs, with the cardiovascular system being particularly vulnerable. Recent research highlights the significance of readily available blood markers in predicting myocardial damage in children infected with MP.

The Culprit: How MP Infection Leads to Myocardial Injury

The exact mechanisms by wich MP infection leads to myocardial injury are still under investigation, but two primary pathways are suspected:

• Direct invasion: MP can directly invade epithelial cells, increasing vascular permeability and stimulating T cells and macrophages.This process induces inflammatory cells to secrete pro-inflammatory cytokines, ultimately causing myocardial injury.
• Indirect Immune Damage: Some MP antigens share structural similarities with cardiomyocyte surface proteins. This similarity can lead to cross-immune reactions, triggering autoantibodies that attack myocardial tissue. MP can directly invade epithelial cells, increase vascular permeability, stimulate T cells and macrophages, induce inflammatory cells to secrete pro-inflammatory cytokines, and cause myocardial injury; some MP antigens are structurally similar to cardiomyocyte surface proteins, resulting in cross-immune reactions and triggering autoantibodies to attack myocardial tissue

Key Blood Markers: NLR and PNR

Two easily obtainable and cost-effective indices, the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-neutrophil ratio (PNR), are emerging as valuable tools in clinical research. These ratios reflect the interplay between inflammatory cells during MP infection and are associated with immune and coagulation responses in systemic inflammation.

• NLR (Neutrophil-to-Lymphocyte Ratio): An elevated NLR indicates a higher proportion of neutrophils (pro-inflammatory cells) compared to lymphocytes (cells involved in immune regulation). NLR has been used to predict poor outcomes in conditions like sepsis, cancer, and cardiovascular diseases. NLR has now been used to predict poor prognosis in diseases such as sepsis, neoplasms, and cardiovascular diseases
• PNR (Platelet-to-Neutrophil Ratio): A decreased PNR suggests increased interaction between platelets and neutrophils, potentially leading to vascular and organ damage.

Neutrophils and Lymphocytes: A Delicate Balance

During MP infection, neutrophils and lymphocytes play opposing roles in the inflammatory response:

• Neutrophils: These pro-inflammatory cells secrete inflammatory factors, reactive oxygen species (ROS), and proteolytic enzymes. After migrating to the heart, they can cause cardiomyocyte necrosis, vascular endothelial injury, and impaired myocardial perfusion. Neutrophils are pro-inflammatory cells that secrete large amounts of inflammatory factors, reactive oxygen species (ROS), and proteolytic enzymes after migrating to the heart, resulting in cardiomyocyte necrosis, vascular endothelial injury, affecting myocardial perfusion, and causing myocardial damage
• Lymphocytes: Stimulated by inflammation, lymphocytes differentiate into regulatory T cells and secrete anti-inflammatory cytokines like IL-10. These actions reduce the inflammatory response, promote the regeneration of damaged myocardium and vascular endothelial cells, and offer protection during cardiovascular injury. Lymphocytes are stimulated by inflammation to differentiate into regulatory T cells, secrete anti-inflammatory cytokines such as IL-10, reduce the inflammatory response, promote the proliferation and regeneration of damaged myocardium and vascular endothelial cells, and have a protective effect during cardiovascular injury

Study Findings: NLR and PNR as Predictors

A recent study revealed significant correlations between NLR, PNR, and myocardial damage in children with MP infection:

• Elevated NLR: Children with MP-related myocardial damage exhibited significantly higher NLR values compared to those without myocardial damage. This suggests that NLR can serve as an autonomous risk factor for myocardial damage and has predictive value. in this study, we found that NLR was significantly higher in children with MPP myocardial damage than in those without myocardial damage. NLR can be used as an independent risk factor for myocardial damage and has some predictive value.
• Decreased PNR: PNR was significantly lower in children with MP-related myocardial damage. While PNR alone was not a significant predictor in multivariate analysis, it showed a strong negative correlation with inflammatory markers like CRP, CK-MB, and LDH. This study showed that PNR was significantly lower in children with MPP myocardial damage than those without myocardial damage.PNR was negatively correlated with CRP, CK-MB, and LDH.

Platelet-Neutrophil Interactions: A Closer Look

The interaction between platelets and neutrophils plays a crucial role in the inflammatory cascade. Platelet-neutrophil complexes can trigger neutrophil trapping nets (NETs) and ROS release, leading to organ tissue damage. Some studies have found that PNR is decreased in patients with septic shock, and activated platelets interact with neutrophils, both of which together cause vascular and vital organ damage and may trigger shock.

Platelet-neutrophil complexes interact in bacterial sepsis to trigger neutrophil trapping nets (NETs) and ROS release,causing organ tissue damage while eliminating pathogens.
Lisman T. Platelet-neutrophil interactions as drivers of inflammatory and thrombotic disease. Cell Tissue Res. 2018;371:567-76.

Clinical Implications and Recommendations

The study’s ROC curve analysis indicated that a combination of factors, including median age, NLR, PNR levels, and extrapulmonary manifestations, provides the highest diagnostic and predictive value. Specifically:

• Age: Children younger than 6.79 years old are at higher risk.
• Extrapulmonary Manifestations: The presence of conditions like acute sinusitis or acute otitis media increases the risk.
• Blood markers: An NLR greater than 2.41 and a PNR less than 44.74 suggest potential myocardial damage.

Based on these findings, it is recommended that children with MP infection who meet these criteria undergo myocardial enzyme testing and electrocardiography for early detection and treatment.

Limitations and Future Directions

The study acknowledges certain limitations, including the absence of cardiac troponin I (cTnI) measurements, a conventional marker of myocardial injury.However, the specificity of CK-MB was improved by excluding concomitant skeletal muscle injury or other conditions that could lead to CK-MB elevation. The study was also a single-center retrospective study with a limited number of cases included, which may effect the predictive power of NLR, PNR, etc., due to selective bias.

Future research should prioritize larger, multicenter, prospective studies that include cTnI analysis to further validate these results.