| Background:Primary Sjogren’s syndrome(pSS)is a chronic,systemic autoimmune disease characterized by gland dysfunction caused by lymphocyte proliferation and infiltration in exocrine glands.The main clinical manifestations are dry mouth and dry eyes.Some patients will develop systemic symptoms and multi-system organ damage,and the risk of lymphoma increases by about 5%-10%.The exact pathogenesis of pSS is still unclear,and studies have shown that the production of immune complexes and autoantibodies is considered to be the key step.Anti-nuclear antibody(ANA),anti-SSA antibody,anti-SSB antibody and rheumatoid factor(RF)have been widely used in the diagnosis and analysis of pSS,but their sensitivity and specificity are not high,which often lead to missed diagnosis.In recent years,researchers have found a variety of new antibodies,including aquaporin antibodies,in pSS,and their mechanisms need to be further studied.Aquaporins(AQP)are widely expressed in exocrine glands,and it has been confirmed that AQP5 plays a key role in salivary secretion.Therefore,we speculate that anti-AQP antibody has a certain relationship with the pathogenesis of pSS.Objective:To explore the diagnostic value of antibody against aquaporin-1(anti-AQP1)and antibody against aquaporin-5(anti-AQP5)in patients with pSS.To search for new potential serological diagnostic biomarkers.Methods:A prospective controlled study was conducted to collect 70 patients with pSS and other connective tissue diseases(CTD)from the Department of Rheumatology and Immunology of the First Affiliated Hospital of Army Medical University from September 2021 to March 2022.The patients were divided into pSS group(n=70),CTD group(n=67)and healthy control group(n=39).The concentrations of anti-AQP1 and anti-AQP5 in serum were detected by enzyme linked immunosorbent assay(ELISA).receiver operating characteristic curve(ROC)was drawn to analyze the clinical diagnostic value of serum anti-AQP1 and anti-AQP5.the best cut-off value,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),Youden index and area under the cure curve(AUC)were calculated.At The same time,The EULAR Sjogren’s syndrome disease activity index(ESSDAI)score was used to evaluate the pSS patients.According to ESSDAI score,the disease activity was divided into 3 grades.Low activity was defined as ESSDAI<5,moderate activity as ESSDAI 5≤ESSDAI≤13,and high activity as ESSSDAI≥14.In addition,the patient’s peripheral blood laboratory test data were collected.Including ANA,anti-SSA antibody,anti-SSB antibody,anti-Ro52 antibody,ds-DNA,RF,fodrin antibody,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),complement C3,white blood cell(WBC),platelet(PLT),hemoglobin(Hb),lymphocyte(Lym),creatinine(Cr),alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Clinical examination results were also collected,including unstimulated saliva flow rate(≤1.5 ml/15min was defined as decreased,>1.5ml/15min was defined as normal),OSS score(≥5 was defined as positive),labial gland biopsy(It is suggested that there is a focal lymphocytic infiltration in the labial gland,and the focal index≥1 lesion/4 mm~2 is positive)and salivary gland secretion function radionuclide imaging.The relationship between anti-AQP1,anti-AQP5 and ESSDAI,clinical symptoms,related tests and examination results was analyzed by correlation statistical method.Results1.Comparison of peripheral blood laboratory results between pSS group(n=70)and CTD group(n=67):The positive rates of anti-SSA antibody,anti-SSB antibody,ANA,anti-Ro-52 antibody and RF in pSS group were higher than those in CTD group(P<0.05).The test results of CRP,WBC and PLT in CTD group were higher than those in pSS group(P<0.05).There were no significant differences in the test results of ds-DNA,fodrin antibody,complement C3,ESR,Hb,Lym,Cr,ALT and AST between the two groups(P>0.05).2.Comparison of peripheral blood serum levels of anti-AQP among pSS group(n=70),CTD group(n=67)and healthy control group(n=39):The concentrations of anti-AQP1 in the three groups were 27.11(18.74,28.89)ng/ml,27.31(25.43,28.17)ng/ml and 24.44(10.77,28.68)ng/ml respectively.pSS group>healthy control group(P<0.05),CTD group>healthy control group(P<0.05),and there was no significant difference in concentration between pSS group and CTD group(P>0.05).The concentrations of anti-AQP5 in the three groups were 26.41(24.05,28.08)ng/ml,9.10(7.62,22.13)ng/ml,5.91(3.13,6.90)ng/ml respectively,pSS group>CTD group>healthy control group(P<0.05).3.Comparison of peripheral blood serum levels of anti-AQP between pSS group(n=70)and control group(n=106,including 67 cases of CTD group and 39 cases of healthy people):The concentrations of anti-AQP1 in the two groups were 27.11(18.74,28.89)ng/ml and26.46(22.91,28.18)ng/ml respectively,and there was no significant difference between the two groups(P>0.05).The concentrations of anti-AQP5 in pSS group and control group were26.41(24.05,28.08)ng/ml and 7.63(5.49,10.29)ng/ml respectively.The level of anti-AQP5in PSS group was significantly higher than that in control group(P<0.05).4.ROC curve analysis of blood serum levels of anti-AQP between pSS group(n=70)and control group(n=106,including 67 cases of CTD group and 39 cases of healthy people):The area under the ROC curve of anti-AQP1 serum level was 0.523(P>0.05),the Youden index was 0.098,the best cut-off value was 28.11ng/ml,the sensitivity was 0.371,the specificity was 0.726,the PPV was 0.473,and the NPV was 0.636.The area under the ROC curve of anti-AQP5 serum level was 0.915(P<0.05),the Youden index was 0.778,the best cut-off value was 14.81ng/ml,the sensitivity was 0.957,the specificity was 0.821,the PPV was 0.779,and the NPV was 0.967.5.In pSS group(n=70),there was no correlation between serum levels of anti-AQP1 and anti-AQP5 and ESSDAI disease activity score(P>0.05).ESSDAI disease activity score showed that 8 cases were low activity,42 cases were moderate activity,and 20 cases were high activity.There was no significant difference in anti-AQP1 and anti-AQP5 levels among different pSS disease activity(P>0.05).6.In pSS group(n=70),62 cases had dry mouth symptoms and 8 cases had no dry mouth symptoms.There was no significant difference in serum anti-AQP1 and anti-AQP5 levels between the dry mouth group and the non-dry mouth group(P>0.05).There were 45 cases with dry eye symptoms and 25 cases without dry eye symptoms.The serum concentration of anti-AQP1 in the dry eye group was lower than that in the non-dry eye group(P<0.05),and there was no significant difference in the serum level of anti-AQP5 between the two groups(P>0.05).7.There was no significant correlation between the serum levels of anti-AQP1 and anti-AQP5 and salivary gland flow rate,salivary gland secretion function radionuclide imaging,OSS score and pathological biopsy results of labial glands in pSS patients(P>0.05).8.In pSS group(n=70)and CTD group(n=67),there was no significant correlation between serum anti-AQP1 level and anti-SSA antibody,anti-SSB antibody,ANA,anti-Ro52antibody,RF,ds-DNA,fodrin antibody(P>0.05).The serum level of anti-AQP5 was positively correlated with anti-SSA antibody,anti-Ro52 antibody,anti-SSB antibody,ANA and RF(P<0.05).There was no correlation between anti-AQP5 and ds-DNA,fodrin antibody(P>0.05).Conclusion:1.Serum anti-AQP5 level was significantly increased in pSS patients,with a sensitivity of 95.7%and a specificity of 82.1%.It has high potential clinical diagnostic value and may become a new serological diagnostic marker for pSS.2.Serum anti-AQP1 level is higher in patients with pSS and other connective tissue diseases than in healthy adults.Serum anti-AQP1 level is lower in pSS patients with dry eye symptoms,and its clinical value is worthy of further exploration.3.There was no correlation between serum anti-AQP1,anti-AQP5 levels and ESSDAI disease activity. |
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