Role of serum amyloid A in Mycoplasma pneumoniae pneumonia and related respiratory diseases

Abstract

Serum amyloid A (SAA) is an acute-phase protein that can increase in plasma concentration by up to 1000-fold during infection and inflammation. Clinical studies have identified significantly elevated SAA levels in Mycoplasma pneumoniae pneumonia (MPP), correlating with disease severity, lung injury, and prognosis. Emerging evidence indicates that SAA is not merely a passive inflammatory biomarker but an active contributor to MPP pathogenesis, which engages receptors such as formyl peptide receptor 2 (FPR2), Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), and the receptor for advanced glycation end products (RAGE) to intensify the inflammatory response. The proposed Community-Acquired Respiratory Distress Syndrome (CARDS) toxin-NLR family pyrin domain containing 3 (NLRP3)-Interleukin-1 β (IL-1 β )-SAA amplification loop synthesizes evidence from disparate experimental systems into a coherent mechanistic hypothesis; however, this pathway has not been experimentally verified in a single integrated model, and each component has been demonstrated independently rather than as a functional loop. SAA has demonstrated diagnostic and predictive value in MPP, with reported area under the curve(AUC) values of 0.942 for MPP diagnosis and 0.735 -0.872 for predicting refractory MPP(RMPP) across studies with variable designs; however, detailed performance metrics, including 95% confidence intervals (CIs), study populations, and sample sizes are limited by inconsistent reporting in the source literature. SAA is induced within 4–6 hours post-infection, more rapidly than C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6); however, its limited specificity requires interpretation alongside clinical findings and other biomarkers. Moreover, SAA plays context-dependent roles in various pulmonary diseases, such as chronic airway diseases, interstitial lung diseases, acute infectious pneumonias, and acute lung injury. The dual nature of SAA—protective at low levels but pathogenic when persistently elevated—presents a therapeutic challenge: balancing acute-phase host defense with the prevention of chronic inflammatory damage. This review consolidates current knowledge on SAA structural biology, high-density lipoprotein (HDL)-associated regulation, receptor-mediated signaling, and clinical applications in MPP. It also examines SAA roles across pulmonary diseases, cellular sources, mechanisms of action, and emerging therapeutic strategies targeting SAA-mediated pathways.