The Analysis Of Interleukin-35 With Clinical Significance In Patients With Primary Sj(?)gren’’s Syndrome

ObjectivesTo explore the serum levels of interleukin-35 and clinical significance in primary Sj?gren’s syndrome(pSS),analyze its potential role in the pathogenesis of primary Sj?gren’s syndrome,and provide new ideas for clinical treatment.Methods120 cases of serum samples of hospitalized pSS patients were collected from June 2014 to May 2017,in China-Japan Union Hospital of Jilin University(all patients were female),all patients were recorded with general information such as age,height,weight and disease duration;clinical characteristics such as dry mouth,dry eyes,the positive condition of corneal staining,tear flow,tear film breaking time,and the damaged degree between the salivary glands and the submandibular glands,and other extraglandular manifestations,such as oral ulcers,fever,fatigue,Raynaud’s phenomenon,joint involvement;and laboratory indexes such as blood routine,liver function,blood lipid,immunoglobulin(IgA,IgG,IgM)and complement(C3,C4),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),rheumatoid factor(RF),antinuclear antibody series,antineutrophil cytoplasmic antibody(ANCA)and anticardiolipin antibody(ACL).We calculated the disease activity score according to ESSDAI for all patients.30 age-and gender-matched healthy controls were also enrolled from the Physical Examination Center of the hospital.The serum levels of IL-35 and IL-17 of the experimental group and the control group(HC)were detected by enzyme-linked immunosorbent assay(ELISA)method,differences between the two groups were analyzed,then the relationships between the serum levels of thetwo cytokines and the clinical indexes of the 120 patients were also evaluated;furthermore,we divided the 120 patients into two groups: on the basis of ESSDAI standard proposed by Seror’s et al.,the pSS group was divided into disease activity group(group Ac-SS,ESSDAI > 2)and stable disease group(group St-SS,ESSDAI≤ 2),we analyzed the difference between the two groups;ILD group(group ILD)and non ILD group(group n-ILD)were further divided according to whether there was lung involvements,the difference between the two groups were also analyzed.Results1.When compared with the healthy control group,the serum levels of IL-35 in the SS group was significantly lower,and the level of serum IL-17 was significantly higher,the differences were statistically significant(both P < 0.001).2.The serum levels of IL-35 in HC group were negatively correlated with age.In the SS group,(1)the levels of serum IL-35 were negatively correlated with age,ESSDAI,NLR,PLT,Glb,ESR and CRP(P < 0.01);the serum levels of IL-17 were only positively correlated with NLR and PLT(P < 0.05);while there were no obvious correlation with age,ESSDAI,Glb,ESR or CRP(P > 0.05).(2)there was a negative correlation between the serum levels of IL-35 and IL-17(P = 0.001).3.(1)When compared with St-SS group,the Ac-SS group has elder age of onset(p=0.001),the disease duration in Ac-SS group was longer than that in St-SS group,but there was no statistically significant difference(P > 0.05);there was no statistically significant difference between the two groups of the positive ratio of corneal staining,the ratio of the appearance of oral ulcers,fever,fatigue,Raynaud’s phenomenon,and joint involvement,either(P > 0.05).(2)compared Ac-SS group with St-SS group,Alb,Glb,ESR and CRP were significantly different(P < 0.01);there was no significant difference between the two groups among PLT,IgG,IgA,IgM,C4(P > 0.05).(3)the ratio of positive ANCA in Ac-SS group was significantly increased than that in St-SS group(P < 0.05);there was no significant difference in the ratio of positive anti-SSA antibody,positive anti-SSB antibody and positive anti-RO-52 antibody between the two groups(P > 0.05).4.(1)the ILD group were significantly elder in the onset age and significantly higher ESSDAI score when compared with n-ILD group(p<0.001);the disease duration was longer while there was no statistically significance(P > 0.05);in comparison of glandular and extraglandular manifestations like the positive ratio of corneal staining,the ratio of the appearance of oral ulcers,fever,fatigue,Raynaud’s phenomenon,and joint involvement between the two groups,there was no statistically significant difference(P > 0.05).(2)compared the ILD group with n-ILD group,the concentration of Alb,IgM,ESR and CRP were significantly different(p< 0.05).There was no statistically significant difference between the two groups in IgG,IgA and C4(P > 0.05).(4)compared with n-ILD group,the ratio of positive anti-SSA antibody was significantly lower while the ANCA positive ratio was significantly higher in SS-ILD group(P < 0.05);however,there was no statistically significant difference between the two groups in the ratio of positive anti-SSB antibody and the ratio of positive anti-RO-52 antibody(P > 0.05).(5)The difference of serum IL-35 levels among ILD group,n-ILD group,and HC group was significant(P < 0.001),the serum IL-35 levels in ILD group and n-ILD group were significantly decreased when compared with healthy controls(P < 0.001);the serum levels of IL-35 in ILD group was even lower than that of n-ILD group(P < 0.05).The difference of serum IL-17 levels among ILD group,n-ILD group,and HC group was also significant(P < 0.001),The serum IL-17 levels in ILD group and n-ILD group were significantly higher than those in HC(P < 0.001),but there was nosignificant difference of serum IL-17 levels between ILD group and n-ILD group(P > 0.05).ConclusionsThis was the first study we found that serum levels of IL-35 in pSS patients were significantly lower than healthy controls,and the serum levels of IL-35 showed a significantly negative correlation with ESSDAI and the serum IL-17,which indicate that IL-35 can be used to evaluate the SS disease activity index;the study also showed that serum IL-17 levels in patients with pSS were significantly higher than healthy controls,suggesting that the broken of balance between IL-35 and IL-17 may be involved in the pathogenesis of SS.This was the first study found that the serum levels of IL-35 in pSS patients with ILD was significantly lower than those pSS patients without ILD and healthy people;when compared with n-ILD group,the ESSDAI score,the serum concentrations of ESR,CRP were significantly increased while the Alb level was significantly decreased in ILD group,indicating that IL-35 may be involved in the pathogenesis of SS-ILD.This study may provides new ideas for the pathogenesis and treatment of in SS patients and SS-ILD patients.