Correlation Studies On Clinical Characteristics And Biomarkers In Patients With Systemic Vasculitis

Objective:Recently,with the improvement of screening methods for hypertension,increasingly number of elevated blood pressure have been proved to be one of the clinical symptoms of some diseases in the process of occurrence and development.Systemic vasculitis(SV)has been proved to be one of the important causes of resistant hypertension and malignant hypertension.Because of its various clinical manifestations and lack of specific biomarkers for diagnosis and disease assessment.Therefore,it is very difficult to diagnose,distinguish the active and remission stages,evaluate the therapeutic effect and predict recurrence.This study retrospectively analyzed the hospitalized patients diagnosed with SV in the People’s Hospital of Xinjiang Uygur Autonomous Region,and deeply analyzed the demographic characteristics,clinical manifestations and related laboratory examinations of SV and its subgroups,so as to improve the clinicians’ understanding of SV.The expression levels of erythrocyte distribution width(RDW)?high mobility group box 1(HMGB1),lysosome-associated membrane protein-2(LAMP-2)and its autoantibodies in patients with SV were further studied.The correlation of RDW,HMGB1,LAMP-2 and its autoantibodies with clinical indicators of SV was analyzed,and the clinical diagnostic and disease evaluation value of RDW,HMGB1,LAMP-2 and its autoantibodies were assessed.Methods:Part Ⅰ:Two hundred and eighty-seven cases of SV patients hospitalized in People’s Hospital of Xinjiang Uygur Autonomous Region from January 2010 to December 2016 were collected,including 170 cases of ANCA-associated vasculitis(AAV),73 cases of polyarteritis nodosa(PAN)and 44 cases of takayasu arteritis(TA).Record the demographic data,clinical manifestations and laboratory test results of SV patients.Statistical analysis of the clinical characteristics of SV and its subgroups were performed.Part II:To investigate the clinical significance of red blood cell distribution width(RDW)in SV and its subgroups according to clinical data.Part III:Eighty-six patients with SV were selected from the Center for Hypertension of People’s Hospital of Xinjiang Uygur Autonomous Region from January 2013 to December 2018.During the same period,46 EH patients and 86 HC matched with age and sex were recruited.All clinical data and serum samples were collected.Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay(ELISA).The levels of IL-8 and IL-23 in serum was detected by flow cytometry.To observe the changes of serum HMGB1 levels in SV and its subgroups,and its correlation with clinical indicators.Part IV:The serum LAMP-2 and its autoantibodies levels were detected by ELISA,and the differences of serum LAMP-2 and its autoantibodies among subgroups were observed.To analyze the relationship between serum LAMP-2 and its autoantibodies levels and clinical indicators.To further evaluate the value of combined diagnosis with regard to LAMP-2 and its autoantibodies in differential diagnosis of SV patients in hypertensive population.Results:Part I:SV patients can be seen in any age,of which 30-40 years old and 51-60 years old are the most common,the ratio of morbidity between male to female is about 1:1.In SV subgroups,the age of AAV patients was mainly over 50 years old,and t there is no difference between genders,odds ratio of morbidity is 1:1;the age of PAN patients was mainly distributed between 31 and 60 years old,and the ratio of male to female was about 1:1,male slightly more than that of female;the age of TA patients was mainly under 40 years old,and the ratio of male to female was about 1:2.2.In addition,renal involvement,hypertension and fever were the most common first clinical symptoms in patients with SV.In SV subgroups,renal and lung involvement,hypertension were the most common initial clinical manifestations of AAV.However,the most common first clinical manifestations of PAN and TA patients were hypertension,fever and headache.Renal involvement is the most common clinical manifestation in patients with SV,followed by hypertension.In SV subgroups,renal involvement,lung involvement and hypertension were the most common clinical manifestations in AAV patients;renal involvement,hypertension and headache were the most common clinical manifestations in PAN patients;hypertension,headache and fever were the most common clinical manifestations in TA patients.Further,the SV patients with hypertension were divided into grade I-III according to the blood pressure levels.The results showed that the blood pressure levels of AAV patients with hypertension was mainly in grade I-II,while that of PAN and TA patients with hypertension was mainly in grade II-III.In SV subgroups,the levels of white blood cell(WBC),erythrocyte sedimentation rate(ESR),high-sensitivity C-reactive protein(Hs-CRP)and serum creatinine(Scr)in AAV patients were significantly higher than those in PAN and TA patients,while the levels of red blood cell(RBC)and hemoglobin(HB)in AAV patients were significantly lower than those in PAN and TA patients.Part II:The RDW levels in active SV was markedly increased compared with inactive SV and HC.In addition,the RDW levels of SV patients with renal injury was significantly increased than in patients with non-renal injury and HC.The correlation analysis showed that RDW was positively correlated with birmingham vasculitis activity score(BVAS),Hs-CRP,ESR,Scr and WBC,and negatively correlated with HB.RDW is an independent risk factor for the occurrence of SV active stage.Part III:Serum HMGB1 levels in SV patients was higher than in EH and HC,and there was no significant difference between EH and HC.Serum HMGB1 levels in active SV patients was significantly higher compared with inactive SV patients,and was positively correlated with BAVS and Hs-CRP.Serum HMGB1 levels in SV patients with renal injury was significantly increased than in patients with non-renal injury,and was positively correlated with Scr and 24 hours proteinuria.To further evaluate the correlation between HAMGB1 and cytoinflammatory factors.The results showed that serum HMGB1 levels was not correlated with IL-8 and IL-23.Subgroup analysis showed that serum HMGB1 in PAN was significantly higher than in AAV and TA,and was positively correlated with Scr and 24 hours proteinuria.Logistic regression analysis showed that HMGB1 was an independent risk factor for SV.Part IV:Compared with EH and HC,serum LAMP-2 and its autoantibodies levels in patients with SV increased significantly.Serum LAMP-2 and its autoantibodies levels in active SV patients were significantly higher than those in patients with inactive and HC,and positively correlated with BAVS and Hs-CRP.Logistic regression analysis showed that serum LAMP-2 and its autoantibodies were risk factors for patients with SV and active stage.The sensitivity and specificity of LAMP-2 combined with its autoantibodies for diagnosis of SV were 76.5%and 95.7%,respectively.The sensitivity and specificity of LAMP-2 and its autoantibodies for diagnosis of active SY were 71.4%and 81.3%,respectively.Conclusion:Part Ⅰ:SV patients can be seen at any age,of which 30-40 years old and 51-60 years old are the most common.In SV subgroups,AAV patients were mainly distributed middle-aged and elderly people over 50 years old,PAN patients were mainly middle-aged and young people aged 31-60 years old,TA patients were mainly young women under 40 years old.Renal involvement is the most common in SV patients,especially in AAV patients.Hypertension is also common in SV patients,especially in PAN and TA patients with severe hypertension,which should be paid enough attention by clinicians.In some SV patients,especially PAN and TA patients,inflammatory markers may not be directly proportional to the severity of the disease and vascular lesions.In addition,AAV patients are more likely to suffer from anemia than PAN and TA patients.Part II:RDW levels were significantly increased in patients with SV and could reflect the disease activity and renal involvement of SV.In addition,high RDW levels may be a risk factor for SV active stage.Part III:Serum HMGB1 levels was significantly increased in patients with SV,and can reflect the active stage of SV and severity of renal injury.In addition,serum HMGB1 levels in PAN patients were significantly higher than those in AAV and TA patients,and were positively correlated with Scr and 24 hours proteinuria.HMGB1 may be a potential biomarker of SV,which can be helpful for clinical diagnosis,disease assessment and differential diagnosis of SV in hypertensive population,especially in PAN.Part IV:Serum LAMP-2 and its autoantibodies levels were significantly higher in patients with SV than those in EH and HC,and could reflect the disease activity of SV.The combined diagnosis of LAMP-2 and its autoantibodies has high sensitivity and specificity.As new biomarkers,LAMP-2 and its autoantibodies has certain value in the diagnosis of SV,and the evaluation of active stage and the differential diagnosis of SV in hypertensive population.