Normal Reference Intervals of Neutrophil-To-Lymphocyte Ratio, Platelet-To-Lymphocyte Ratio, Lymphocyte-To-Monocyte Ratio, and Systemic Immune Inflammation Index in Healthy Adults: a Large Multi-Center Study from Western China

Background: Numerous studies have shown that the hematological components of the systemic inflammatory response, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune inflammation index (SI') are efficient prognostic indicators in patients with cancers. Most of the studies did not investigate the reference intervals (RIs) of these parameters in healthy controls. Methods: A retrospective cohort study was performed on healthy ethnic Han population aged between 18 and 79 years of age by retrieving the data from a healthy routine examination center database and laboratory information system of four participating centers in western China. By following the Clinical and Laboratory Standards Institute (CLSI), RIs of each parameter was established and validated. Results: The analysis included 5,969 healthy subjects. We found that the individual's gender can significantly influence PLR, LMR, and SII (all p < 0.05), but not NLR (p > 0.05). Surprisingly, we also found that with an increase in age, the PLR, LMR, and SII tend to decrease, while NLR remained stable. PLR, LMR, and SII values were significantly higher in the young adults (18 - 64 years) than in old adults (65 - 79 years) (p < 0.001). The RIs of NLR, PLR (adults), PLR (old adults), LMR and SII were 0.88 - 4.0, 49 - 198, 42 - 187, 2.63 - 9.9, 142 x 10(9)/L 804 x 10(9)/L, respectively. Conclusions: Our study addresses possible variations and establishes consensus for the NLR, PLR, LMR, and SIIRIs for healthy Han Chinese adults in western China. Further, established RIs can standardize clinical applications and promote the use of these indicators into the routine complete blood count report.