| Background and objectiveInterstitial lung disease(ILD),also known as diffuse pulmonary parenchymal lung disease(DPLD),is a group of more than 200 diseases.In recent years,the incidence of ILD has been increasing.Many of the ILDs treated in respiratory medicine are caused by rheumatic immune diseases.Sjogren syndrome(SS)is one of the more common causes.SS is a systemic,chronic,and progressive inflammatory syndrome.It is characterized by lymphocyte infiltration leading to dysfunction of the exocrine glands.The cause is not yet clear.The common clinical manifestations are dry eyes and dry mouth,but often cause other systemic organs to be involved in the course of disease development.If SS occurs alone,it is called primary Sjogren syndrome(pSS);if it is secondary to other systemic autoimmune diseases(such as systemic sclerosis,rheumatoid arthritis,and forced spine)Inflammation,etc.)is referred to as secondary Sjogren syndrome(sSS).This article focuses on pSS.ILD is the most common pulmonary manifestation of pSS.Up to 60%of patients have evidence of ILD,pSS patients with ILD have 39%mortality,and almost 50%of deaths are directly caused by ILD.The gold standard for the diagnosis of ILD is pathology.However,many patients with suspected ILD cannot obtain a lung biopsy because of critical illness,surgical risk,etc.Therefore,the identification of diagnostic biomarkers for ILD will help clinicians and patients,especially if lung biopsy is not available.In recent years,the use of biological markers to diagnose and evaluate ILD is a hot research field.The human type II alveolar cell surface antigen(krebs Von den Lungen-6,KL-6)is a macromolecular glycoprotein with a relative molecular weight of approximately200,000 Daltons.It belongs to the ninth group of lung cell antigens and belongs to the class of mucins.Because the MUC1 family mainly consists of type II alveolar epithelial cells in the lungs,it is also called alveolar type II cell surface antigen-6 and is produced and secreted in bronchial gland serous cells and respiratory bronchial epithelial cells.The National Health Program of Japan approved KL-6 as a diagnostic marker for ILD and included KL-6 in the diagnosis and treatment guidelines for ILD diseases such as pneumonia and idiopathic interstitial pneumonia.This article mainly observes and analyzes the clinical application value of KL-6 in patients with pss complicated with ILD.Research methodsFrom February 2016 to December 2017,36 cases of pSS combined with ILD in the First Affiliated Hospital of Zhengzhou University and 24 cases of simple pSS patients were collected,and 24 healthy people with age and gender matched were selected.The hospital ethics committee approved the research program.The diagnostic criteria of pSS:ACR and EULAR in 2017 jointly published in Arthritis Rheumatology new diagnostic pSS criteria:to meet the two inclusion criteria and exclusion criteria,and the score of?4 patients can be diagnosed as pSS.ILD is based on lung function tests,imaging studies,or lung biopsy.Exclusion criteria:(1)previous history of radiotherapy for head,neck,and chest;(2)combined with bronchial asthma,chronic obstructive pulmonary disease,pulmonary embolism,cystic fibrosis,and other lung diseases;(3)unexplained or clear causes of pneumoconiosis,etc.ILD;(4)combined with other rheumatic diseases;(5)pulmonary infections(including obsolete or Pulmonary tuberculosis);(6)lung tumors.The levels of serum KL-6 in 36 patients with pSS and ILD,24 patients with pSS alone,and 24 normal controls were determined by ELISA.Follow-up study of pSS patients with ILD.General information,clinical manifestations,laboratory tests,imaging examinations,ophthalmic examinations,dental examinations,lung function,etc.were collected from selected patients.The correlation between serum KL-6 and the above indicators was analyzed.And monitor serum KL-6 to observe whether it has a diagnostic significance,the prognosis,whether it can guide treatment.SPSS 19.0 statistical software was used for statistical analysis of collected data.Measured data are in accordance with the normal distribution of mean±standard deviation(x±s).The t-test was used to compare the mean values of the two sets of data with a normal distribution and a uniform variance.Quantitative data between groups were compared using one-way ANOVA.Pairwise comparisons of multiple sets of samples were performed using the LSD-t test.Chi-square test was used to compare the count data.Sensitivity and specificity analysis apply receiver operating curve(ROC).Spearman's linear correlation analysis was used for correlation analysis.P<0.05 was statistically significant.Results1.There was no statistical difference in gender and age between 36 patients with pSS and ILD,24 patients with pSS alone,and 24 healthy individuals.There was no significant difference in the course of disease between pSS patients with ILD and patients with pSS alone(P>0.05).2.Among the 60 patients,there were 34 cases(56.67%)with dry eyes,22 cases(36.67%)with dry mouth,19 cases(32.67%)with Raynaud's phenomenon,20 cases(33.33%)with low fever,and parotid gland swelling.Eighteen patients(30.00%)had joint pain,5(8.33%)had joint pain,19(31.67%)had cough,and 26(43.33%)had chest tightness.There were no significant differences in dry mouth,dry eyes,Raynaud's phenomenon,fever,parotid gland enlargement,and joint pain in the first symptoms of patients with pSS combined with ILD and pSS alone(P>0.05).The cough and chest tightness were statistically different(P<0.05).3.The serum CRP concentration in patients with pSS and ILD was significantly higher than that in the serum of pSS group and healthy control group(P<0.05).The serum concentration of PCT in the normal control group was significantly higher than that in the pSS combined ILD group and the pSS group(P<0.05).The serum erythrocyte sedimentation rate,white blood cell,red blood cell,hemoglobin,and platelet concentrations in patients with pSS and ILD were not significantly different from those in the pSS alone group and the normal control group.The positive rate of ANA antibody in patients with pSS and ILD was 77.8%,which was significantly higher than that in patients with PSS alone(37.5%).There was a significant difference between the two groups(P<0.05).The positive rate of anti-SSA(Ro)antibody in patients with pSS and ILD was 69.4%,which was significantly higher than that in patients with PSS alone(33.3%).There was a significant difference between the two groups(P<0.05).The positive rate of anti-SSB antibody in patients with pSS and ILD was(69.4%),which was significantly higher than that in patients with pure PSS(3.3%).There was a statistically significant difference between the two groups(P<0.05).4.RV,TLC,FEV1 and DLCO were higher in pSS without ILD compared with pSS and ILD,and the difference was statistically significant(P<0.05).DLCO was compared between the two groups:The DLCO was higher in the pSS alone group than in the pSS and ILD group.There was a significant difference between the two groups(P<0.05).FEV1/FVC was not considered statistically significant(P>0.05)between patients with pSS and pSS with ILD.5.Clinically,serum KL-6?500U/ml is the diagnostic positive standard.A total of28 pSS patients with ILD group had a positive rate of 77.78%(28/36).The positive rate was 8.3%(2/24)higher than that in the pSS alone group and 14.29%(3/24)in the normal control group.The mean values of serum KL-6 in the pSS-combined ILD group,the pSS-only group,and the healthy normal group were(815.83±404.48)U/ml,(366.25±147.27)U/ml,(360.46±127.31)U/ml,respectively.After one-way ANOVA,the pSS was combined with ILD.Serum KL-6 levels in the group were significantly higher than those in the pSS alone group and the healthy normal group,with a significant difference(P<0.05).There was no significant difference in the concentration of serum KL-6 between the pSS group and the healthy control group(P>0.05).Statistical analysis of the receiver operating characteristic curve(ROC curve)showed that the critical value of serum KL-6 in the diagnosis of pSS and ILD was496.5 U/ml,and the area under the curve(AUC)was 0.843.The 95%confidence interval(CI)was(0.744 to 0.943),the sensitivity was 80.6%and the specificity was88.9%(P<0.05).6.The Spearman correlation analysis showed that serum KL-6 concentration and RV(r=-0.394,P<0.05),TLC(r=-0.672,P<0.05),TLCO(r=-0.581,P<0.05)in patients with pSS and ILD.0.05)FEV1(r=-0.435,P<0.05),FEF50(r=-0.316,P<0.05),MMEF(r=-0.355,P<0.05),showed a significant negative correlation.There was a positive correlation with HRCT fibrosis score(r=0.51,P<0.05).There was no significant correlation with FEV1/FVC(r=0.202,P>0.05)and FEF75(r=-0.151,P>0.05).7.There was no significant difference in the positive rate of ANA antibody(X~2=0.046,P>0.05),anti SSA(Ro)antibody(X~2=0.150,P>0.05),and anti SSB antibody(X~2=1.833,P>0.05)between the serum KL-6 elevated group and the normal KL-6 group in the patients with pSS combined with ILD.8.Follow-up pSS patients with ILD 5 to 24 months,of which 6 patients died,the average serum KL-6 measured at the time of the initial diagnosis of death and surviving patients was(1256.71±246.47)U/ml,survival group(709.41±362.16)U/ml,the difference has Statistical significance(t=4.763,P<0.05).9.Follow up of 7 cases of pSS combined with ILD for half a year,the clinical symptoms improved after treatment,and the chest HRCT improved or no progress.The mean serum KL-6 concentration was(638.71±264.59)U/ml and(351.71±164.56)U/ml before and after treatment.The serum KL-6 was statistically significant(t=5.180,P<0.05)before and after treatment.Conclusions1.Serum KL-6 can be used as a serological marker for diagnosing pSS combined with ILD.2.Detection of serum KL-6 may reflect the degree of HRCT and pulmonary function impairment in patients with pSS and ILD.3.High levels of serum KL-6 suggest poor prognosis of pSS with ILD.4.Serum KL-6 can evaluate the clinical efficacy of patients with pSS combined with ILD. |
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