The Correlation Between Neutrophil-to-lymphocyte Ratio & Platelet-to-lymphocyte Ratio And Graves’ Disease & Graves’ Ophthalmopathy

Objectives:Complete blood count-derived parameters have been a subject of high interest among researchers which is cost-effective,easily-accessible and commonly used indices over the past decade.Neutrophils are treated as the active components of inflammation,whereas lymphocytes are involved in regulatory and protective pathways.Several studies have proved neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)as novel biomarkers of chronic subclinical inflammation in infection,tumor and autoimmune diseases.However,Literature data about the role of NLR and PLR in chronic autoimmune thyroid diseases are still lacking.Graves’ disease(GD)is a common autoimmune thyroid disease.Graves’ ophthalmopathy(GO)constitutes the major extra thyroidal manifestation of GD.GO is an autoimmune inflammatory disorder affecting orbital soft tissue,which may lead to the visual disturbances due to extraocular muscle involvement,proptosis,conjunctival inflammation and oedema.The clinical course of GO is commonly mild to moderate,and the incidence of severe sight-threatening form ranges from 3% to 5%.There is a great need to investigate early biomarkers to identify GD patients with high risk of GO development since patients with subclinical ocular involvement are usually more than those confirmed GO.Our study aimed to explore the relation of NLR and PLR to clinical and laboratory characteristics of patients diagnosed with GD without or with GO,and to analyze association of these parameters with development and grade of GO in GD patients.Methods:The research enrolled 153 patients hospitalized in the Endocrinology Department of the second hospital of Dalian Medical University during the period between January2018 and December 2020.GD patients were divided into two groups based on the presence(GO(+),n=66)or absence(GO(-),n=87)of GO.The control group consisted of 90 randomly selected,healthy individuals with normal thyroid function who had the same age and sex that matched the research group.Then all the cases were taken the morning fasting venous blood,in which the free thyroid glycine(FT3)and free thyroxine(FT4),thyroid stimulating hormone(TSH),thyroid stimulating hormone receptor antibody(TRAb),thyroglobulin antibody(Tg Ab),thyroid peroxidase antibody(TPOAb)and complete blood count were tested.All p value less than 0.05 was considered to be statistically significant.The activity of GO was graded according to Clinical Activity Score.The severity of GO was rated as mild,moderate-to-severe and sight-threatening using the European group on Graves’ orbitopathy criteria.All analyses were performed using SPSS program version 17.0.Results:1.Compared with the control group,platelets in GD group slightly higher than those in the control group,while lymphocytes were significantly lower,and NLR(P =0.046),PLR(P = 0.000)and MLR(P = 0.021)in GD group were higher than those in the healthy control group,and the difference was statistically significant.2.There was no significant difference between GO(+)group and GO(-)group in WBC,monocyte,platelet,PLR and MLR,but the levels of white blood cells,neutrophils,NLR and PLR in GO(+)group were higher than those in GO(-)group,but only WBC [GO(-)vs.GO(+),4.91(3.94-6.29)vs.6.62(4.93-8.39)],neutrophils[GO(-)vs.GO(+),2.50(1.78-3.35)vs.3.80(2.39-5.51)] and NLR [GO(-)vs.GO(+),1.30(0.92-1.77)vs.1.89(1.30-2.80)] with statistical difference(P < 0.05).3.Multivariate logistic regression showed that higher GO risk was associated with increased leukocyte count(OR,1.229;95% CI,1.024-1.474;P = 0.026),neutrophils(OR,1.349;95% CI,1.079-1.688;P = 0.009)and NLR(OR,1.222;95% CI,1.009-1.481;P = 0.040).In screening high-risk patients with GO,the best cut-off value of NLR in the receiver operator characteristic analysis was 1.62,the sensitivity was 65.2%,specificity was 71.3%.The proportion of patients with active GO in high NLR group was significantly higher than that in low NLR group(P =0.039).In terms of severity grading,mild(60.87%)was the main group in the low NLR group,while the proportion of mild(23.26%)and moderate severe(72.09%)in the high NLR group was the same.There was significant difference in severity grading between the two groups(P = 0.008).Conclusions:1.Compared with normal people,the levels of NLR and PLR were higher in GD and GO patients,especially in GO patients.2.The level of neutrophils may be related to the development of GO.White blood cell count,neutrophils and NLR are independent factors related to the development of GO in patients with GD.NLR may be helpful to the screening of high-risk patients with GO.3.In different groups of patients,the high NLR group had a higher incidence of GO,and the proportion of mild GO patients was smaller.It suggests that NLR can be used as a new marker to guide the clinical evaluation of patients with GD and GO.