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Objective To evaluate the maternal and fetal outcomes of pregnant women with lupus nephritis (LN) and the risk factors.Methods Ninety-three patients with 97 pregnancies from January 1st,1990 to December 31st,2012 in Peking Union Medical College Hospital were evaluated retrospectively.Objects of study were divided into three groups:stable lupus before pregnancy (stable group,52 cases),active lupus before pregnancy (active group,26 cases),and newly diagnosed LN during pregnancy (19 cases).Adverse maternal outcomes included exacerbated disease during pregnancy,preeclampsia,increased proteinuria and impaired renal function during pregnancy or postpartum,maternal death,thrombocytopenia and hypocomplementemia.Adverse fetal or neonatal outcomes included therapeutically termination of pregnancy,fetal loss,neonatal death,preterm labor,small gestational age and asphyxia.Statistical analysis was performed by Chi-square test or Fisher's exact test.A binary logistic regression model was used to evaluate the risk factors for adverse maternal and fetal outcomes.Results (1) Adverse maternal outcomes:There was no significant difference between exacerbated cases during pregnancies in stable group and that in active group [53.8 ％ (28/52) vs 61.5 ％ (16/26),x2 =0.417,P＞0.05].After deleting abortions before 20 weeks of gestation (5 cases in stable group and 4 cases in active group),there was no significant difference between preeclampsia incidence in stable group and that in active group [36.2％ (17/47) vs 59.1％ (13/22),x2 =3.204,P＞0.05].In nineteen newly diagnosed LN women,eighteen cases were over 20 weeks of gestation,during which preeclampsia incidence was 6/18.(2) Adverse fetal or neonatal outcomes:Therapeutically termination of pregnancy rate was higher in active group than that in stable group[42.3％(10/26) vs 7.7％(4/52),Fisher's exact test,P＜0.01].After deleting patients who required termination of pregnancy (three cases in stable group) and therapeutically termination of pregnancy (four cases in stable group and ten cases in active group),the rate of fetal loss and neonatal death was higher in active group than that in stable group [5/16 vs 6.7％(3/45),Fisher's exact test,P＜0.05].The rate of adverse fetal or neonatal outcomes was higher in active group than that in stable group [92.3％(24/26) vs50％(26/52),x2=13.483,P＜0.001].Among the nineteen newly diagnosed LN cases during pregnancy,the numbers of therapeutically termination of pregnancy and fetal loss were five and three cases respectively; among eleven live birth cases,two newborns died from severe asphyxia,and nine cases were preterm birth.(3) Binary logistic regression analysis showed that the independent risk factors for exacerbated lupus during pregnancy were hypocomplementemia (OR =0.300,95％ CI:0.104-0.863) and thrombocytopenia (OR =0.054,95％CI∶0.007-0.439).The independent risk factors for preeclampsia in LN pregnant women were thrombocytopenia (OR=0.151,95％CI:0.046-0.499) and LN recurrence or first diagnosed during pregnancy (OR=0.135,95％CI:0.027-0.679).The independent risk factors for adverse fetal or neonatal outcomes were preeclampsia (OR=0.134,95％CI:0.028-0.637) and lupus active during pregnancy (OR =0.026,95 ％ CI:0.005-0.138).Conclusions Active lupus before pregnancy is associated with poor maternal and fetal outcomes in lupus nephritis pregnancy.All pregnancies with LN should be planned,preferably after more than six months of quiescent disease.Blood pressure,renal function,proteinuria and level of platelet and serum complements should be closely monitored.
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Objective To investigate the expression of T cell immunoglobulin domain and mucin domain (TIM)-3 and its ligand Galectin-9 in the peripheral blood of initial systemic lupus erythematosus (SLE)patients,and explore their effects on SLE.Methods The percentages of CD4+TIM-3+,CD8+TIM-3+cells from 33 SLE patients and 26 normal controls were detected by flow cytometry,and the Galectin-9 gene expression of PBMCs was determined by real-time PCR The SLE Disease Activity Index(SLEDAI),C3 level and lymphocyte count were evaluated.Mann-Whitney U test was used for independent samples analysis and Spearmen's test was used for correlation analysis.Results The percentages of CD4+TIM-3+ and CD8+TIM-3+ cells were markedly increased in SLE group than those of the control group(P<0.01).In particular,the CD4+TIM-3+,CD8+TIM-3+ level Was positively correlated with SLEDAI (r=0.517,P＜0.01;r=0.400,P＜0.05);but negatively correlated with C3(r=0.487,P＜0.05;r=0.395,P＜0.05).The Galectin-9 mRNA in SLE PBMCs was higher than that of the controls(P<0.05).Conclusion TIM-3-Galectin-9 pathway may be involved in T cell immune regulation of SLE,and is related to disease activity.
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Objective To detect the methylation status of p16 gene promoter in CD4~+ T cells of patients with systemic lupus erythematosus(SEE),and its significance in the pathogenesis of SLE.Methods The pl 6 gene promoter methylation in peripheral CD4~+ T cells was detected with the Taqman probe-based realtime PCR(Methylight)technology in 28 patients with SLE and 20 healthy human controls.Results The methylation rate of p16 gene promoter in peripheral CD4~+ T cells was higher in patients with SLE than that in the controls(35.7%VS 10%,x~2=4.11,P<0.05).There was no correlation between SLE disease activity index (SLEDAI)and the normalized index of methylation(NIM)of p16 gene promoter(r_s=-0.29,P>0.05).Conclusion The methylation status of p16 gene promoter is aberrant in CD4~+ T,:ells of SLE patients,suggesting that the hypermethylation of p16 gene plays a certain role in the pathogenesis of SLE.
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Objective To investigate the immunoregulatory effects of mesenchymal stem cells (MSCs)on peripheral blood T lymphocytes from patients with systemic lupus erythematosus(SLE)in vitro and their potential mechanism.Methods MSCs were isolated from the bone marrow of 3 healthy human volunteers,cultivated and identified.Under phytohemagglutinin(PHA)stimulating,peripheral blood T lymphocytes from 8 patients with SLE were treated with MSCs with the T lymphocyte/MSC ratio being 50:1 in group B and 5:1 in group C or without MSCs(group A).MTT assay was used to detect the proliferation of T lymphocytes.flow cytometry to analyze the expressions of surface markers CD152 and CD28 on T lymphocytes.and real time PCR to measure the mRNA expressions of interleukin-6 and interferon-γ,in the T lymphocytes.Results MSCs could markedly inhibit the proliferation of T lymphocytcs.The proliferation of T lymphocytes expressed as absorbance value at 570 nm was 0.484±0.032 in group B.0.308±0.025 in group C,significantly lower than that in group A(0.765±0.036,both P＜0.05),and significant difference was also observed between group C and B(P＜0.05).In the case of the percentage of CD28 positive T lymphocytes.group B and C were significantly lower than group A(60.39%±3.92%and 45.05%±3.46%vs 74.73%±3.74%,both P＜0.05),and group B significantly differed from group C(P＜0.05).MSCs had no obvious effect on the expression of CD152 on T lymphocytes,but significantly suppressed the mRNA expression of interleukin-6 and interferon-γ(both P＜0.05).and the suppressive effect was enhanced with the incrgase in MSC count.ConclusionsMSCs exert an immunosuppressive effect on T lymphocytes from patients with SLE,likely through inhibiting the proliferation,CD28 expression,interleukin-6 and interferon-γ mRNA expression of T lymphocytes.