In previous studies, recently developed inflammatory and immunological indicators such as NLR and the platelet-to-lymphocyte ratio (PLR) have been verified as diagnostic makers of disease activity and severity in various disorders. Peng et al. indicated that the combined use of NLR, PLR and CEA could represent a good diagnostic biomarkers for colorectal cancer, and positive correlations were found between the TNM stage and NLR or PLR[15]. In addition, Zhao et al. also observed that NLR was correlated with knee recurrence after arthroscopic surgery combined with local radiotherapy [16]. A recent study of rheumatoid arthritis (RA) patients with and without rheumatoid arthritis-associated interstitial lung disease (RA-ILD) by Chen et al. revealed that PLR and NLR exhibited a statistically significant positive correlation with DAS28 and PLR could be used to diagnose RA and RA-ILD and distinguish RA-ILD patients from RA patients and healthy subjects[17].
In recent years, another indicator LMR has attracted considerable attention in the diagnosis and prognosis of many diseases such as cancers or various immunological diseases. Rajwa et al. found that urothelial bladder cancer patients treated with radical cystectomy with lower LMR values exhibited a greater risk for developing postoperative in-hospital complications[18]. Du et al. showed that the LMR was an inflammatory marker that is effective in disease activity evaluation in patients with RA and RA differentiation from other arthritis condition[19].
The present study revealed a decreased LMR in axial SpA patients compared to healthy controls, especially in axial SpA patients with high X-ray stages. Furthermore, the correlations between LMR and other axial SpA related indicators revealed that LMR was positively correlated with RBC, Hb, Hct and A/G and negatively correlated with NLR, PLR, AST and TBIL.
Anemia is a common phenomenon in the process of chronic inflammation and is also found in axial SpA patients, and the mechanisms were attributed to the inhibitory effects of cytokines secretion. Tumor necrosis factor alpha(TNF-α) could block the effects of Erythropoietin(EPO) on CD34(+) hematopoietic stem/progenitor cells[20]. Increased hemoglobin level were observed in axial SpA patients with significant improvement of physical function and fatigue [21]. Thus, hemoglobin levels could reflect axial SpA activity and severity. Specifically, reduced Hb levels indicate reduced disease severity.
As a major component in serum protein, serum albumin was used to reveal long-standing malnutrition and was also associated with systemic inflammation[22]. Globulin is the carrier of sex hormones, and globulin levels combined with levels of pro-inflammatory proteins (including complement components, immunoglobulin, CRP, interleukin, TNF) are reflective of the inflammatory state[23]. A/G is based on serum albumin and globulin levels and reflects immunonutritional status and systemic inflammatory reactions with more accuracy compared with either indicator alone.. A higher A/G value indicates a good malnutrition status and low hormone levels. Besides, Lin et al also showed that a low A/G level was significantly correlated with high total bilirubin levels but low hemoglobin levels [24]. These results were consistent with the results obtained in this study.
Lymphocytes play an important role in immunology. Although different subsets of T cells are associated with poor tumor prognosis [25, 26], high absolute lymphocyte counts are associated with good prognosis in gastric cancer patients [27]. An increased number of monocytes was associated with poor prognosis in various types of tumors[28, 29].
Monocytes could differentiate into tumor-associated macrophages (TAMs) in the tumor microenvironment[30]. TAMs could promote tumor angiogenesis and tumor growth by secreting TNF-α[31]. Therefore, LMR may be associated with a good axial SpA prognosis because a higher of LMR could result in reduced inhibitory effects of TNF-α on EPO secretion as well as higher hemoglobin levels and A/G ratios. In contrast, lower NLR, PLR, total bilirubin levels and direct bilirubin levels were also observed, supporting the results of this study.
Liver toxic effects could result from systemic rheumatic diseases and therapeutic drugs. Hepatic involvement is a severe type of extra-articular manifestations in various rheumatic diseases. Hepatotoxicity is commonly observed with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modified anti-rheumatic drugs (DMARD) as immunosuppressants[32]. In our study, we only included axial SpA patients who were treated by NSAIDs; Therefore, the negative correlation between LMR and AST was reasonable.
Regarding the correlations we observed between axial SpA and LMR, we further discussed the diagnostic value of LMR in axial SpA prognosis. ROC curve analysis showed that LMR had a high diagnostic value for axial SpA second only to ESR and CRP. The combined diagnostic AUC of LMR, ESR and CRP for axial SpA was 0.975 with a sensitivity and specificity of 94.9% and 97.4%, respectively. Based on X-ray staging, axial SpA patients were divided into the non-radiographic axial SpA and radiographic axial SpA groups. WBC and NLR levels were higher in the radiographic axial SpA groups, whereas LMR levels were lower. Based on these observations, it can be inferred that LMR is associated with the X-ray stage of sacroiliitis in axial SpA patients.
The relationship between LMR and X-ray staging in axial SpA is rarely reported in previous publications. In our research, we classified axial SpA patients as stage I to IV according to X-ray imaging to discuss the associations between LMR and the severity of sacroiliitis. The value of LMR decreased as X-ray staging increased, indicating the role of LMR in determining axial SpA severity.
The main limitation of our study was it only assessed patients from a single center.. Therefore, multicenter prospective study is needed for further verification of our results. Secondly, we could not obtain scoring criteria related to axial SpA activity such as BASDAI and ASDAS activity indexes, given the lack of or incomplete clinical datas of axial SpA patients. Third, the sample size was relatively small given the low prevalence and we only included axial SpA patient treated by NSAIDs in the present study. Fourth, most of axial SpA patients included in the study exhibited a lower stage of activity and disease severity, and more sensitive imaging techniques are needed.