Construction Of Pathological Pregnancy Prediction Model And Study Of Pathogenesis In Systemic Lupus Erythematosu

Part Ⅰ:Prediction model for adverse pregnancy outcomes in patients with systemic lupus erythematosus based on a prospective multi-center cohort in ChinaObjective:This study aimed to explore predictors of different types of adverse pregnancy outcomes(APOs)in systemic lupus erythematosus(SLE)based on a prospective multicenter SLE cohort,and construct prediction models for total APOs,major APO types and disease fare,respectively.Methods:All SLE patients with regular follow-ups and pregnancy outcomes recorded from July 2010 to April 2022 were included.Baseline characteristics were collected.LASSO regression was used,combined with univariate analysis and previous studies,to screen predictors of total APOs,fetal loss,preterm delivery and disease flare during pregnancy or within half a year postpartum,respectively.Then we developed 3 prediction models for each outcome,calculating net reclassification index(NRI)and concordanceindex(C-index)to obtain the optimal one,and evaluate it by internal validation.All models were presented by nomograms,forest plot and scoring systems.Results:A total of 545 pregnancies were included in the study.Fetal loss and preterm delivery rate were 18.9%and 20.1%,respectively.Final prediction model for total APO included 10 predictors:BMI,arthritis history,thrombocytopenia history,SDI≥1.late spontaneous abortion history,hematuria,proteinuria and rash at baseline,hydroxychloroquine and initial glucocorticoid dose.Model predicting fetal loss included 7 predictors:hypertension,anti-β2GPI antibody,C4 reduction,hematuria and disease flare at baseline,hydroxychloroquine and aspirin.Model predicting preterm birth included 8 predictors:BMI.arthritis history,thrombocytopenia history,late spontaneous abortion history,hematuria,proteinuria and disease flare at baseline and initial glucocorticoid dose.Model predicting lupus flare included 10 predictors:duration,lupus nephritis history.hemolytic anemia history,renal damage,hypertension,LA,PLT reduction,C3 reduction and anti-dsDNA at baseline.C-index ranged 0.704-0.733.Brier score ranged 0.133-0.208.Conclusion:We constructed 4 risk prediction models for pregnant SLE patients,all with good discriminability and stability.Based on the models,we also developed 4 practical risk scoring systems,which could support the risk stratification and individualized management in SLE pregnancies to a great extent.Part Ⅱ:Pathological features and immune cell subsets structure of maternal-fetal interface in systemic lupus erythematosus pregnancyObjective:This study aimed at exploring the pathological abnormalities and overall immune cells composition of maternal-fetal interface in pregnancy of systemic lupus erythematosus(SLE),with the focus on potential effects of monocyte-macrophage and natural killer(NK)cells on the maternal-fetal interface in SLE patients.Methods:Placenta samples of SLE patients,patients with antiphospholipid syndrome(APS)or positive antiphospholipid antibody(aPL+),and health controls were sequentially collected from Peking Union Medical College Hospital.Hematoxylin-eosin(HE)staining was used to describe pathological differences of placenta among the three groups.Flow cytometry was utilized to analyze distinctions of the proportions of T cells,B cells,monocytes,NK cells and neutrophils in the maternal and fetal surfaces of placenta,respectively.Then we furtherly analyzed NK cell subsets constitution in placenta of the three groups.Finally,we did immunohistochemistry(IHC)using anti-CD 163 antibody and anti-interlukine-10(IL-10)to explore the polarization of mononuclear-macrophage system in the maternal-fetal interface of SLE patients.Results:HE staining experiments included 10 SLE patients,10 APS/aPL+patients and 7 health control.Neutrophil infiltration,severer calcification and bleeding area,as well as manifestations suggesting placenta malperfusion including reduction and dilation of villous capillaries,edema of villi were found more frequently in placenta biopsies of SLE and APS/aPL+patients compared to health control.Flowcytometry analysis included 3 SLE patients,2 APS/aPL+patients and 2 health controls.A higher proportion of monocytes(maternal side 24.2%vs 14.7%,fetal side 28.6%vs 8.6%)and cytotoxic CD56dimCD16+NK cells(maternal side 27.5%vs 20.4%,fetal side 39.9%vs 11.4%)were seen in placentae of patients.And IHC suggested fewer CD163+M2 macrophage and less IL-10 secretions in placenta of SLE patient.Conclusion:In this study,we summarized the pathological findings in placenta of SLE patients,preliminarily analyzed the immune cell subsets at maternal-fetal interface and suggested the potential roles of macrophages and NK cells in the occurrence of adverse pregnancy outcomes in SLE.