Analysis Of Clinical Features Of Cerebrovascular Disease In Systemic Lupus Erythematosus And Research On Gut Microbiota Of The Relative Cognitive Impairment

BackgroundNeuropsychiatric systemic lupus erythematosus(NPSLE)is one of the serious complications of systemic lupus erythematosus(SLE),associated with a high mortality rate.Cerebrovascular disease is a common subtype of NPSLE,which can be divided into large vessel disease(LVD)and small vessel disease(SVD).LVD refers to cerebral infarction or hemorrhage in the large artery region,and thrombosis of cerebral vein,while SVD mainly include white matter hyperintensity,lacunes,brain atrophy,etc.Until now,The risk factors and pathogenesis of SLE-CVD have not yet been elucidated.SLE-SVD patients often suffer from cognitive impairment,which greatly affects the quality of life.And the etiology is unknown.In recent years,studies have found that gut microbiota is associated with the pathogenesis of post-stroke cognitive impairment.But whether it is also involved in the pathogenesis of related cognitive impairment of SLE-SVD has not yet been reported.Objective1.To analyze the clinical manifestations and laboratory indicators,and explore the possible risk factors of SLE-CVD by a retrospective study.2.To explore the role of gut microbiota in the onset of cognitive impairment of SLE cerebral small vessel disease by analyzing the characteristics of gut microbiota.Methods1.A total of 199 SLE patients was enrolled retrospectively,including 61 patients in the SLE non-cerebrovascular disease(SLE-nCVD)group,138 patients in the SLE-CVD group.Among the 138 patients,53 were large vessel disease(SLE-LVD),85 were the small vessel disease(SLE-SVD).Compared the clinical manifestations and laboratory indicators between the groups,and analyzed independent risk factors using multi-category Logistic regression.2.A total of 29 patients with SLE-SVD were prospectively enrolled.According to the results of the Montreal Cognitive Assessment,11 patients were in the non-cognitive impairment(SLE-nCI)group,and 18 patients were in the cognitive impairment(SLE-CI)group.Collect stool samples from patients for 16S rRNA sequencing.The gut microbiota of healthy people,SLE-nCI and SLE-CI patients were transplanted into C57BL/6J mice.After fecal microbiota transplantation,Morris water maze experiment was conducted to evaluate the cognitive function.ResultsCompared with the SLE-nCVD group,the SLEDAI-2000 score in the SLE-CVD group was higher.The SLE-LVD group are mainly cerebral infarction,and the SLE-SVD group are mainly white matter hyperintensity(WMH).Multinomial Logistic Regression showed that LA positive(OR=1.087,95%CI:1.068-1.194,P=0.008)and β2GP1-IgG(OR=1.027,95%CI:1.018-1.042,P=0.030)are the independent risk factors of SLE-LVD.And ACA-IgM(OR=1.092,95%CI:1.009-1.185,P=0.036),β2GP1-IgG(OR=1.024,95%CI:1.001-1.047,P=0.037)are the independent risk factors for SLE-SVD,HDL-C(OR=0.258,95%CI:0.075-0.889,P=0.032)is its protective factor.The Chao1 index and Faith’s PD index of the gut microbiota between SLE group and the healthy control(HC)group are significantly different,And Adonis analysis showed R2=0.046,P<0.001.Fusobacteriota,Fusobacterium,Gemella,Lactobacillus,and Streptococcus are significantly enriched in the SLE group,While the abundances of Lachnospira and clostridioides are significantly decreased.After FMT,the a and βdiversity of mice in HC group,SLE-nCI group,and SLE-CI group were significantly different,and the mice transplanted with the gut microbiota of SLE-CI patients showed a decline in spatial learning and memory in the Morris water maze.ConclusionLA positive and β2GP1-IgG are independent risk factors of SLE-LVD.ACA-IgM and β2GP1-IgG are independent risk factors of SLE-SVD,while HDL-C is the protective factor.Gut microbiota may be involved in the onset of cognitive impairment of SLE-S VD patients.