| Objective:In this study,we started single-center cohorts of systemic lupus erythematosus(SLE)related intestinal pseudo-obstruction(IPO)and protein losing enteropathy(PLE)to investigate clinical characteristics,risk factors,survival situation and prognosis factors.The case control study of SLE was also conducted to reveal different enteric microbiota patterns in several SLE subtypes.This part of study aims to shed light on the value of enteric microbiota in SLE onset,diagnosis and treatment.The multi-center inception cohort of SLE was established and analyzed cross-sectionally in order to lay a solid foundation for prognosis research.Methods:This study involved SLE-related IPO and PLE patients in Peking Union Medical College Hospital(PUMCH)from 1997 to 2016 retrospectively.Baseline time was set as clinical diagnostic time.Baseline data including demographics,family history,clinical characteristics,and immunological indexes were collected and follow-up research in which endpoint events were death or recurrence was finished.Life table method and Kaplan-Meier estimator with log-rank test were used to analyze cumulative probabilities of the endpoints.After single risk factors were identified statistically significant,COX regression multivariate analysis was also conducted to identify independent prognostic factors.In the study of enteric microbiota,fecal samples of SLE gastrointestinal involvement,lupus nephritis and neuropsychiatric SLE patients were collected and analyzed by 16s ribosome DNA sequencing to identify bacterial population.The differences of enteric microbiota between SLE subtypes and healthy control were reached by comparison.About prognostic research of multi-center inception cohort,patients in Chinese systemic lupus erythematosus treatment and research group(CSTAR)who got enrolled after SLE onset in less than 6 months were included.Demographics,family history,clinical characteristics,and immunological indexes were collected as baseline data and cross-section analysis was conducted.Results:1.Gastrointestinal involvements of SLE include SLE-related IPO and PLE.Respectively 133 and 58 patients were enrolled with a female predominance of 92.48%and 79.31%.The patients were aged between 11 and 71 years old.About 43.61%to 53.45%of patients presented IPO or PLE as initial manifestation of SLE.(1)The main symptom of SLE-IPO was intestinal obstruction.Urinary symptoms also occurred in 21.05%to 24.06%patients.Serositis were found in 63.91%of patients as the most common involved system.Besides,63.16%,21.80%and 57.14%of patients had complications in renal,neural and hematological systems.The positive rate(66.17%)of anti-SSA antibody was the highest and low complements were reported in 84.96%of patients.About 52.63%of patients had pyeloureterectasis.In this group of patients,involvement of bladder wall(42.86%vs 6.35%,P<0.001),hepatobiliary dilatation(14.29%vs 3.17%,P=0.026)and serositis(78.57%vs 47.62%,P<0.001)were more common than the group without pyeloureterectasis.Among them,some patients had triad symptoms of hollow organs dilation.Serositis(OR=10.114,P=0.000),neuropathy(OR=4.336,P=0.000),positive anti-SSA antibody(OR=2.092,P=0.014),positive anti-SSB antibody(OR=2.433,P=0.035)and low complements(OR=2.685,P=0.003)were risk factors of SLE-related IPO.About treatment,all patients received corticosteroid therapy and 50.38%of them underwent corticosteroid pulse therapy.85.71%of patients were treated with CTX.The prognosis of SLE-IPO was poor with 1,3 and 5-year overall survival rate of 91.51%?89.46%?86.73%.Themain death cause was infection,accounting for 53.33%.Cumulative recurrence rate of 1,2 and 3-year was 14.71%,26.32%and 37.04%.Independent prognostic risk factors included late onset(HR= 1.051,P=0.027)and neuropathy(HR=4.621,P=0.017).Protective factors including positive anti-SSA antibody(HR=0.530,P=0.039),fist line immunosuppressive agents at early stage(HR=0.209,P=0.020)and early remission(HR=0.530,P=0.039)could improve overall survival and prognosis of SLE-IPO patients.(2)SLE-PLE patients had hypoalbuminaemia(100%),peripheral edema(89.66%)and pleural effusion(77.59%)as main clinical features.One third of patients had no gastrointestinal symptoms..99mTc HAS test for diagnosis indicated the most common site of protein leakage was small intestine.The positive rate of anti-SSA antibody was 51.72%and low complements were reported in 87.93%of patients.One,three and five-year overall survival rate was 91.49%,91.49%and 88.54%.Infection(40.00%)and active lupus(40.00%)were main death causes.Severe hypoalbuminaemia(x2=9.061,P=0.003)and elevated 24h urine protein(HR=1.553,P=0.012)were prognostic risk factors.Early recognition,diagnosis and enhanced supportive treatment could improve prognosis of SLE-PLE patients.2.Twelve cases of SLE gastrointestinal involvement,lupus nephritis and neuropsychiatric SLE patients respectively and seven cases of healthy control were enrolled.Comparison analysis of intestinal microbial communities at the level of phylum,family,genus and species indicated that different subtypes and healthy people differed in their enteric microbiota.Gastrointestinal involvement and lupus nephritis patients had less Firmicutes(42.48%,49.37%vs 60.61%)and more Proteobacteria(43.29%,17.61%vs 8.72%).In gastrointestinal involved patients,enteric microbiota was particularly disordered.The proportion of Firmicutes and Bacteroidetes was only 50.39%,while Proteobacteria(43.29%vs 8.73%,P=0.021),Enterobacteriaceae(42.54%vs 6.79%,P=0.018)and Escherichia-Shigella(36.03%vs 2.61%,P=0.040)were enriched significantly.3.There were 1514 patients enrolled in the multi-center inception cohort of SLE.Among them,1370 patients were female and the rest were male.The average onset age was 31.36.Family history of autoimmune disease was reported in 5.22%of patients and abnormal reproductive history occurred in 16.24%.Comparing prior SLE incident cohort of PUMCH which including 2104 cases,this cohort had later onset age(P<0.001)and diagnostic age(P=0.003).The proportions of malar rash,discoid rash,photosensitivity,oral ulcer,arthritis,serositis,renal,neural and hematological involvement were 49.47%,10.30%,24.97%,23.98%,53.30%,22.85%,46.10%,6.93%and 67.70%respectively.When compared with incident cohort,inception cohort had more serositis(P<0.001),neuropathy(P<0.001)and hematological complication(P<0.001).About autoantibody,positive rates of anti-dsDNA antibody,anti-Sm antibody,anti-SSA and anti-SSB antibody were 39.36%,22.66%,32.16%and 10.96%which were lower than those in incident cohort(P<0.001).Conclusion:This study established clinical cohort of SLE-related gastrointestinal involvement for the first time.The comprehensive description of this rare subtype revealed that SLE-IPO patients had more serositis and higher anti-SSA antibody positive rate.Risk factors of SLE-IPO included serositis,neuropathy,positive anti-SSA and SSB antibody and low complements.Five-year overall survival rate was 86.75%while cumulative recurrence of 3-year was 37.04%.Late onset and neurological complication were prognostic risk factors.Meanwhile,anti-SSA antibody was protective factor.Usage of first line immunosuppressive agent at early stage and early remission could improve overall survival and prognosis of SLE-IPO patients.Enteric microbiota in different subtypes of SLE are various.The diversity of intestinal microbial communities were weakened in gastrointestinal involved and lupus nephritis patients with less Firmicutes and more Proteobacteria.Reconstruction of balanced enteric microbiota could benefit SLE patients probably.The cross-sectional analysis of newly established SLE inception cohort indicated clinical features of Chinese SLE patients which laid a solid foundation for further prognostic study. |
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