The Correlation Between The Expression Of Serum Intestinal Mucosal Barrier Function Markers With The Lymphocytes Subsets In Peripheral Blood Of Patients With Systemic Lupus Erythematosus

Background: Systemic lupus erythematosus(SLE)is an autoimmune disease characterized with the abnormal immune tolerance and the production of autoantibodies,which can lead to various clinical manifestations and damage to important organs.However,the exact mechanism is still unclear.As one of the components of the mucosal immune system in body,the intestinal mucosal barrier function has received extensive attention.It can play a barrier function and maintain the immune homeostatic microenvironment.Studies have found that the dysfunction of intestinal mucosal barrier can promote the local inflammatory responses and allow a variety of antigens,toxins,pathogens to pass through the intestinal mucosal barrier to activate immune cells and produce pro-inflammatory factors,resulting in abnormal immune responses and loss of immune tolerance.It may be closely related to the development of autoimmune diseases such as SLE.However,there are few studies on the role of intestinal mucosal barrier in SLE.Therefore,our study will focus on the changes of intestinal mucosal barrier function in SLE patients and analyze the correlation with the development of the disease by detecting the expression of serum intestinal mucosal barrier markers in SLE,in order to provide new insights into the pathogenesis and immunomodulatory treatment of SLE.Objective:By comparing the differences in serum intestinal mucosal barrier function markers between patients with SLE and healthy controls,as well as that between different disease activity groups of patients with SLE to evaluate the impairment of intestinal mucosal barrier function and the relationship with disease severity.Furthermore,by analyzing the correlation between the changed serum intestinal mucosal barrier function markers with the clinical indicators of the disease,lymphocyte subsets,CD4+T cell subsets in peripheral blood and cytokine expression in patients with SLE to discuss the role of intestinal mucosal barrier function in the progression of disease,and provide the basis for target therapy of SLE.Methods: 1.The clinical data of 45 patients with SLE were retrospectively collected who met the inclusion criteria and were hospitalized in our department from September 2020 to January 2021,and the disease activity was evaluated according to the SLEDAI score.They were divided into the group with and without gastrointestinal symptoms according to the presence or absence of digestive tract-related symptoms(abdominal distention,constipation,abdominal pain,nausea,vomiting,and diarrhea).The differences of disease activity and clinical indexes between the two groups were compared.2.30 patients with SLE who were inpatient or outpatient treatment in our department from February 2021 to October 2021 and met the inclusion criteria were included.At the same time,10 healthy controls were collected as the healthy control group(HC group).The demographic data of the two groups were collected,and the laboratory indexes of SLE patients(including ESR,CRP,C3,C4,anti-ds-DNA antibody,etc.)were collected.The SLEDAI score was calculated to evaluate the disease activity of patients with SLE.According to the SLEDAI score,patients with SLE were divided into disease activity group(SLEDAI≥5)and non-disease activity group(SLEDAI<5).The expression levels of serum intestinal mucosal barrier function markers(zonulin,IFABP,LPS,LBP)in patients with SLE and healthy controls were detected by enzyme-linked immunosorbent assay.The number of peripheral blood lymphocyte subsets and CD4+T cell subsets were detected by flow cytometry,and plasma cytokines were detected by flow-liquid multiplex protein quantitative technique(CBA).To compare the differences of serum intestinal mucosal barrier function markers between SLE group and HC group,and analyze the correlation with disease activity,clinical indexes,lymphocyte subsets,CD4+T cell subsets in peripheral blood and cytokine expression.Results: 1.The SLEDAI score of SLE patients with gastrointestinal symptoms was higher than that of SLE patients without gastrointestinal symptoms(P=0.001).ESR,CRP and anti-ds-DNA antibody had an upward trend,while C3 and C4 had a downward trend.2.Compared with the healthy control group,the level of serum zonulin [13.33(8.69,28.83)vs5.25(3.78,9.25),P<0.001] and IFABP [2.53(1.87,3.38)vs1.68(1.66,2.01),P=0.004] in the SLE patients were increased.3.Compared with the SLE non-disease active group,the expression level of serum zonulin was significantly higher than that in the SLE disease active group [25.17(16.78,33.99)vs 8.74(6.81,12.60),P<0.001].4.The expression level of serum zonulin in SLE patients was positively correlated with ESR(r=0.424,P=0.020),anti-ds-DNA antibody(r=0.629,P<0.001),and negatively correlated with C3(r=-0.441,P=0.015);the expression level of IFABP was negatively correlated with C3(r=-0.380,P=0.038)and C4(r=-0.432,P=0.017).5.There was a negative correlation between the expression level of serum zonulin and the absolute number of total NK cells in peripheral blood in patients with SLE(r=-0.380,P=0.038).6.There was a positive correlation between the expression level of serum zonulin and IFN-γ in patients with SLE(r=0.561,P=0.015).Conclusion:There is dysfunction of intestinal mucosal barrier in SLE patients.And it is related to disease activity and the production of antibody in SLE.Dysfunction of intestinal mucosal barrier is related to the imbalance of peripheral blood lymphocytes,especially NK cells in SLE patients,which may be one of the reasons for the imbalance of immune homeostasis in SLE patients.