Platelet/Lymphocyte, Lymphocyte/Monocyte, and Neutrophil/Lymphocyte Ratios as Biomarkers in Patients with Rheumatoid Arthritis and Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Chen Q ，Chen DY ，Xu XZ ，Liu YY ，Yin TT ，Li D ... -  《MEDICAL SCIENCE MONITOR》

The clinical value of KL-6 for predicting the occurrence and severity of connective tissue disease-associated interstitial lung disease is not affected by CTD type or treatment.

The aim of this study was to explore the potential values of Krebs von den Lungen-6 (KL-6), neutrophil to lymphocyte ratio (NLR), systemic immune inflammation (SII), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR) and red blood cell distribution width (RDW) in the diagnosis and evaluation of the severity of connective tissue disease-associated interstitial lung disease (CTD-ILD). A total of 140 connective tissue disease (CTD) patients and 85 CTD-ILD patients were recruited for this study at Shanxi Provincial People's Hospital from May 2022 to May 2023. Patients were divided into subgroups based on medication history and CTD subtypes to compare and analyze the clinical data and laboratory parameters of CTD-ILD patients and CTD patients. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of KL-6, NLR, SII, PLR, MLR, and RDW in identifying CTD-ILD patients from CTD patients. A Spearman correlation analysis was conducted to elucidate the correlations between these markers and the lung function parameters of forced vital capacity (FVC, %), forced expired volume in one second (FEV1, %), and diffusing capacity of carbon monoxide (DLCO, %). Finally, binary logistic regression analysis was applied to discern the independent risk factors for CTD-ILD. NLR, SII, MLR, RDW, and KL-6 displayed significant statistical differences in the experimental groups. In both untreated and treated subgroups, KL-6 displayed higher values for CTD-ILD than CTD among all CTD subtypes. In untreated subgroups, there were significant differences in MLR levels between rheumatoid arthritis (RA) and RA-ILD patients and in NLR levels between Sjögren syndrome (SjS) and SjS-ILD patients. There were also significant differences in RDW-SD between the "other CTD" and "other CTD-ILD" groups. In treated subgroups, there were significant differences in both RDW-SD and RDW-CV between RA and RA-ILD patients and in NLR, SII, MLR, PLR, and RDW-SD between "other CTD" and "other CTD-ILD" groups. ROC revealed that KL-6 emerged as the most effective predictor for CTD-ILD in both treated and untreated groups. The multivariate logistic regression analysis results showed that both KL-6 and age were independent risk factors for CTD-ILD. NLR, SII, and PLR were negatively correlated with DLCO (%) in the untreated CTD-ILD group, and KL-6 was negatively correlated with various lung function parameters in both treated and untreated CTD-ILD groups. KL-6 emerged as the most promising biomarker for diagnosing CTD-ILD and assessing its severity. The diagnostic value of KL-6 was unaffected by medication interference and surpassed the value of other parameters, such as NLR, SII, MLR, and RDW. The diagnostic value of RDW-SD was higher than that of RDW-CV in CTD-ILD patients. NLR, SII, MLR, and PLR have potential value in diagnosing the different types of CTD-ILD.

Xing H ，Liang H 《PeerJ》

Multidimensional biomarker approach integrating tumor markers, inflammatory indicators, and disease activity indicators may improve prediction of rheumatoid arthritis-associated interstitial lung disease.

Rheumatoid arthritis (RA) often leads to interstitial lung disease (ILD), significantly affecting patient outcomes. This study explored the diagnostic accuracy of a multi-biomarker approach to offer a more efficient and accessible diagnostic strategy for RA-associated ILD (RA-ILD). Patients diagnosed with RA, with or without ILD, at Beijing Tiantan Hospital from October 2019 to October 2023 were analyzed. A total of 125 RA patients were included, with 76 diagnosed with RA-ILD. The study focused on three categories of indicators: tumor markers, inflammatory indicators, and disease activity measures. The heatmap correlation analysis was employed to analyze the correlation among these indicators. Logistic regression was used to determine odds ratios (OR) for indicators linked to RA-ILD risk. Receiver-operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic potential of these indicators for RA-ILD. The results of logistic regression analysis showed that tumor markers (carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and cytokeratin 19 fragment (CYFRA21-1)), as well as inflammatory indicators (neutrophil, neutrophil-to-lymphocyte ratio (NLR), platelet, C-reactive protein (CRP)) and disease activity measures (disease activity score-28-CRP (DAS28-CRP), rheumatoid factor (RF), and anti-cyclic peptide containing citrulline (anti-CCP)), were significantly associated with RA-ILD. The correlation coefficients among these indicators were relatively low. Notably, the combination indicator 4, which integrated the aforementioned three categories of biomarkers, demonstrated improved diagnostic accuracy with an AUC of 0.857. The study demonstrated that combining tumor markers, inflammatory indicators, and disease activity measures significantly enhanced the prediction of RA-ILD. Key Points • Multidimensional strategy: Integrated tumor markers, inflammatory indicators, and disease activity measures to enhance early detection of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). • Diagnostic accuracy: Employed heatmap correlation and logistic regression, identifying significant associations and improving diagnostic accuracy with a multidimensional biomarker combination. • Superior performance: The combined multidimensional biomarker strategy demonstrated higher diagnostic precision compared to individual or dual-category indicators. • Clinical relevance: Offers a promising, accessible approach for early detection of RA-ILD in clinical settings, potentially improving patient outcomes.

Wan J ，Yu Z ，Cao X ，Zhao X ，Zhou W ，Zheng Y ... -  《-》

The value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as complementary diagnostic tools in the diagnosis of rheumatoid arthritis: A multicenter retrospective study.

The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have drawn attention in recent years as novel non-specific inflammatory markers; however, only a few studies have been conducted to investigate their value in RA. To investigate the value of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as complementary diagnostic tools in rheumatoid arthritis (RA). This study included 1009 patients with RA, 170 patients with other rheumatic diseases, and 245 healthy individuals from four medical centers. The patients' general data, including complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF), were retrospectively analyzed, and the NLR and PLR were calculated. Potential effective indicators were screened by logistic regression analysis, and a receiver operating characteristic (ROC) curve was plotted to evaluate their diagnostic value for RA. (a) The NLR and PLR were significantly higher in the RA group than in the non-RA group and the control group (P < .05). (b) Spearman's Rho showed that the NLR was positively correlated with the PLR (r = .584, P < .05), RF (r = .167, P < .01), and CRP (r = .280, P < .01) but was not significantly correlated with ESR (r = .100, P > .05). The PLR was positively correlated with RF (r = .139, P < .01), CRP (r = .297, P < .01), and ESR (r = .262, P < .05). (c) Logistic analysis showed that RF, CRP, ESR, and the NLR had diagnostic value for RA. (d) For the NLR, the area under the curve (AUC) of the ROC curve was 0.831; at the cutoff value of 2.13, the diagnostic sensitivity, specificity, accuracy, and Youden index were 76.7%, 75.9%, 76.4%, and 0.5424, respectively. The NLR was less effective than CRP and RF but was superior to ESR in the diagnosis of RA. The NLR can thus be used as a complementary diagnostic indicator in the diagnosis of RA.

Jin Z ，Cai G ，Zhang P ，Li X ，Yao S ，Zhuang L ，Ren M ，Wang Q ，Yu X ... -  《-》

Neutrophil-lymphocyte, platelet-lymphocyte and lymphocyte-monocyte ratios may not be useful markers to assess disease activity in rheumatoid arthritis: A STROBE-compliant article.

The associations among the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) and disease activity in rheumatoid arthritis remains unclear.To evaluate these indicators as potential markers of disease activity in patients with rheumatoid arthritis (RA).This cross-sectional study included 547 adult patients with RA. The patients were divided into two groups according to the disease activity score (DAS) system: remission and disease activity. Differences in the NLR, PLR and LMR of the two groups were assessed. Correlations were analyzed using Spearman analysis, and receiver operating characteristic (ROC) curves were used to identify the sensitivity, specificity, and optimal cutoff values to differentiate active RA patients from inactive RA patients.There was a statistically significant difference in the NLR (4.2 ± 3.2 vs 3.4 ± 2.4, P = .034) and PLR (222.3 ± 136.4 vs 176.9 ± 89.8, P = .006) between the two groups, but not for the LMR (3.0 ± 1.8 vs 3.4 ± 2.4, P = .115). In addition, the DAS28 and traditional inflammatory markers, including ESR and CRP, were weakly positively correlated with the NLR and PLR. Based on the ROC curves, the NLR (sensitivity 31.8%, specificity 77.8%) and PLR (sensitivity 57.3%, specificity 63.9%) were less valuable than the ESR (sensitivity 67.2%, specificity 91.7%) and CRP (sensitivity 76.2%, specificity 91.7%) for differentiating inactive RA patients from active RA patients due to low sensitivity and specificity and combining NLR or PLR also cannot significantly improved the diagnostic value of ESR and CRP.NLR, PLR and LMR may not be an useful independent diagnostic or complementary marker for disease activity in RA patients.

Lijuan W ，Yuting Z ，Chaoyang L ，Ju Y ... -  《-》