Ankylosing spondylitis (AS), an immune-mediated chronic inflammatory rheumatic disease with unknown etiology, mainly affects the axial bone and articular structures, but also other parts, such as peripheral arthritis, enthesitis and finger arthritis with extraarticular manifestations like uveitis(Xu, Wang, & Zheng, 2018).The prevalence of AS is about 0.2–0.3%, occurs mostly in males aged 20–30 years. Without effective treatment, Severe disable could be presented in nearly one third of the patients (Arévalo et al., 2018).Until now, the pathophysiology of AS has not been fully understood. Risk factors resulted from heredity, immunity and inflammation are considered as the most important factors in the pathogenesis of AS. In current clinical practice, HLA-B27 is considered as the diagnosis maker for AS due to its 90%-95% high prevalence in AS and its direct role in the onset of AS(Stolwijk, Onna, Boonen, & Tubergen, 2015). Besides HLA-B27, imaging modalities are usually employed in the diagnosis of AS(Bradbury, Hollis, Gautier, Shankaranarayana, & Brown, 2018). However, the radioactive property, relative high expense and limited use in specific patients (such as pregnant women) of imaging facility. Therefore, specific and sensitive biochemical markers for auxiliary diagnosis, treatment guidance and prognosis monitoring of AS are urgently needed.
Traditional inflammatory markers, including ESR and CRP[1], have been verified to be related to the disease activity of AS. ESR × duration of disease and CRP × duration of disease were demonstrated had a good correlation with poor physical activity of AS patients [2].In recent years, some new inflammatory markers, such as Neutrophil-to-lymphocyte ratio (NLR) and RDW, have also been found to be associated with the disease activity of AS. In AS patients, NLR had a good correlation with ESR and CRP, and increased NLR was found in patients with high disease activity[3], whereas difference levels of NLR were found in the patients with different treatment, such as anti-TNF-alpha therapy, and non-steroidal anti-inflammatory drugs[4]. Moreover, there was a significant difference in RDW between patients with BASDAI index > 4 and < 4. RDW was positively correlated with BASDAI index, ESR and CRP levels[3]. Based on the finding, routine blood test indexes could be potential resource for novel and effective marker exploration for AS.
Lymphocyte-monocyte ratio (LMR), similar to RDW and NLR, is also a common blood routine indicator. It has been of great interest in a wide range of fields such as inflammation, immunology and carcinoma for a long period of time. Recent data from several studies suggested that LMR was associated with diagnostic, pretreatment and prognostic statue of diseases. A genome-wide association study has confirmed that mutations in ITGA4 and HLA-DRB1 genes could affect LMR levels and has been widely recognized as susceptible genes for autoimmune diseases, such as rheumatoid arthritis (RA)[5], suggesting its possible employment in AS diagnosis and prognosis evaluation.
To date, few studies have investigated the association between LMR and AS. Therefore, the aim of this essay was to explore the diagnostic value of LMR in AS and its role in reflecting disease activity and X-ray staging of sacroiliac arthritis .
Methods
Patients with AS
A total of 78 patients with AS [51females and 27 males; mean age 41.0 (29–52) years] were enrolled in this retrospective study. These patients were attending the Department of Endocrinology, Taizhou Hospital (Zhejiang, China). All patients fulfilled the AS criteria prescribed by the New York criteria[6],1984. All patients were treated by nonsteroidal anti-inflammatory drugs only. Patients combined with autoimmune diseases such as SS, SLE, RA and psoriasis, malignant diseases, end-stage kidney diseases, liver diseases, acute myocardial infarction, hypertension, diabetes, cerebrovascular diseases were excluded.
Sacroiliac arthritis X-ray staging of the AS Patients
The stage of sacroiliac arthritis was assessed using X-ray and staged from I to IV. Stage I with suspicious sacroiliac arthritis; Stage II with vague margin of sacroiliac joint, slightly sclerotic and minimally invasive lesions, and unchanged joint space; Stage III with moderate or progressive sacroiliac arthritis, accompanied by one or more following changes: sclerosis of proximal articular area, narrowing/widening of joint space, bone destruction or partial ankylosis; and Stage IV with complete joint fusion or ankylosis with or without sclerosis.
Healthy Controls
Healthy controls (HCs) included 55 males and 23 females with a mean age of 40 (30–53) years. These subjects were selected from the Physical Examination Center of Taizhou Hospital (Zhejiang, China) who underwent a physical examination, with features of sex and age match with AS patients. All subjects were healthy without any disease and the absence of drugs that affect bone metabolism, such as hormone replacement therapy.
Biological detection and Imaging system
Fasting blood samples were obtained from all included subjects, whereas X-ray were acquired simultaneously from AS patients. Blood routine test was detected by Mindray BC6800-plus (China) automatic blood analyzer, ESR was detected by ALifax Tes1(Italy) automatic blood analyzer, CRP was detected by Immage 800 (Beckman coulter, USA). ALT, AST, TBIL and Alb/Globin (A/G) were detected by AU5800 (Beckman coulter, USA) automatic biochemical analyzer. X-ray was taken by Digital X-ray imaging system (DR)(Philips, Holland).
Statistical analyses
All statistical analyses were carried out by SPSS version 19.0 (SPSS Inc., Chicago, IL), all graphs were drawn by GraphPad Prism 8. Quantitative and qualitative data were respectively expressed as median (range) or number (percentage). Comparison of between group quantitative and qualitative data was performed using Kruskal-Wallis test and the chi-square test. Receiver operating characteristic (roc) curve analysis with calculation of area under curve (AUC) and 95% confidential interval (CI) was used to determine the role of LMR in the diagnosis of AS. Moreover, optimal cut-off value was calculated Youden's index by for specificity and sensitivity. The correlations between LMR and other indicators was performed by Spearman correlation analysis. P < 0.05 was considered to have statistical significance.