Xiangni Wu

All Publications

• Active tuberculosis in patients with systemic lupus erythematosus from Southern China: a retrospective study. Clinical rheumatology Lao, M., Chen, D., Wu, X., Chen, H., Qiu, Q., Yang, X., Zhan, Z. 2019; 38 (2): 535-543

  Abstract

  To investigate the characteristics and associated factors for Mycobacterium tuberculosis (TB) infection in patients with systemic lupus erythematosus (SLE) from Southern China. A retrospective study of 1108 patients admitted to the First Affiliated Hospital of Sun Yat-Sen University from January 2007 to December 2017 was performed. Demographic and clinical characteristics, laboratory data, and radiographic manifestations were recorded. A total of 59 (5.3%) lupus patients with active TB were included. Pulmonary TB occurred in 41 (69.5%) patients. Single lobe involvement was showed in 14 (34.1%) patients. Multi-lobar involvement, including miliary TB (36.6%), was presented in 27 (65.8%) patients. Lower lobe involvement accounted for 31 (75.6%) of the cases. Extrapulmonary TB occurred in 18 (30.5%) patients. Nearly one-third (35.6%) of the patients developed disseminated TB. T-SPOT.TB assay was performed in 23 patients and positive in 18 patients (78.3%). Nineteen patients (32.2%) had co-infection with TB and other pathogens, most of which were bacterial-associated (52.6%). Lymphopenia was predominant in TB-infected patients, especially in those with disseminated TB. Multivariate logistic regression analysis found that lymphopenia [odds ratio (OR) = 2.19, 95% confidence interval (CI) 1.03-4.63, P = 0.04] and the accumulated doses of glucocorticoid (GC) (OR = 2.32, 95% CI 1.69-3.20, P < 0.001) were associated with TB. TB infection is a common comorbidity in patients with SLE. Manifestations of pulmonary computed tomography (CT) scan are relatively atypical. Co-infection with TB and other pathogens is not rare. Lymphopenia and the accumulated doses of GC are associated with TB infection in lupus patients.

  View details for DOI 10.1007/s10067-018-4303-z

  View details for PubMedID 30244432

• Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study. Arthritis research & therapy Zhou, Y. Z., Zhao, L. D., Chen, H., Zhang, Y., Wang, D. F., Huang, L. F., Lv, Q. W., Liu, B., Li, Z., Wei, W., Li, H., Liao, X., Liu, H., Liu, X., Jin, H., Wang, J., Fei, Y. Y., Wu, Q. J., Zhang, W., Shi, Q., Zheng, W. J., Zhang, F. C., Tang, F. L., Lipsky, P. E., Zhang, X. 2018; 20 (1): 70

  Abstract

  Tripterygium wilfordii Hook F (TwHF) alone or in combination with methotrexate (MTX) has been shown to be more effective than MTX monotherapy in controlling the manifestations in subjects with disease-modifying antirheumatic drug (DMARD)-naïve active rheumatoid arthritis (RA) over a 6-month period. The long-term impact of these therapies on disease activity and radiographic progression in RA has not been examined.Patients with DMARD-naïve RA enrolled in the "Comparison of Tripterygium wilfordii Hook F with methotrexate in the Treatment of Active Rheumatoid Arthritis" (TRIFRA) study were randomly allocated into three arms with TwHF or MTX or the two in combination. Clinical indexes and radiographic data at baseline and year 2 was collected and compared using an intent-to-treat (ITT) and a per-protocol (PP) analysis. Two radiologists blinded to the treatment scored the images independently.Of 207 subjects 109 completed the 2-year follow up. The number of subjects withdrawing from the study and the number adhering to the initial regimens were similar among the three groups (p > = 0.05). In the ITT analysis, proportions of patients reaching American College of Rheumatology 50% (ACR50) response criteria were 46.4%, 58.0% and 50.7% in the MTX, TwHF and MTX + TwHF groups (TwHF vs MTX monotherapy, p = 0.004). Similar patterns were found in ACR20, ACR70, Clinical Disease Activity Index good responses, European League Against Rheumatism good response, remission rate and low disease activity rate at year 2. The results of the PP analysis agreed with those in the ITT analysis. The changes in total Sharp scores and joint erosion and joint space narrowing during the 2 years were associated with changes in disease activity measured by the 28-joint count Disease Activity Score and were comparable among the three groups (p > 0.05). Adverse events were similar in the three treatment groups.During the 2-year therapy period, TwHF monotherapy was not inferior to MTX monotherapy in controlling disease activity and retarding radiological progression in patients with active RA.This is a follow-up study. Original trial registration: ClinicalTrials.gov , NCT01613079 . Registered on 4 June 2012.

  View details for DOI 10.1186/s13075-018-1563-6

  View details for PubMedID 29636089

  View details for PubMedCentralID PMC5894170

• Contribution and underlying mechanisms of CXCR4 overexpression in patients with systemic lupus erythematosus. Cellular & molecular immunology Zhao, L. D., Liang, D., Wu, X. N., Li, Y., Niu, J. W., Zhou, C., Wang, L., Chen, H., Zheng, W. J., Fei, Y. Y., Tang, F. L., Li, Y. Z., Zhang, F. C., He, W., Cao, X. T., Zhang, X. 2017; 14 (10): 842-849

  Abstract

  Aberrant expression of CXCR4 has been indicated to play a role in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanism of CXCR4 dysregulation in SLE is unclear. This study is aimed to explore the clinical significance and possible mechanisms of abnormal CXCR4 expression on B cells from patients with untreated SLE. Expression of CXCR4 on peripheral B cells was determined by flow cytometry and western blotting. Freshly isolated B cells were cultured with exogenous interleukin 21(IL-21) in the presence or absence of CD40 ligand (CD40L) plus anti-IgM antibody (aIgM), and changes in CXCR4 expression were detected. Involvement of phosphatidylinositol 3 kinase (PI3K)/Akt and Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathways was assessed by adding blocking agents Ly294002 and AG490. Since CD63 is reported to mediate endosomal recruitment of CXCR4 and BCL6 is capable of silencing CD63 gene transcription, we also measured BCL6 and CD63 gene transcription with real-time PCR. It was shown that CXCR4 expression on B cells was significantly upregulated in SLE patients, especially in those with lupus nephritis, and was positively correlated with SLE Disease Activity Index scores and negatively with the serum complement 3 levels (P<0.05). Downregulation of CXCR4 by IL-21 was intact. In contrast, a similar effect of aIgM plus CD40L in downregulating CXCR4 expression was defective in SLE patients but was restored by co-stimulation with IL-21 in vitro. Both Ly294002 and AG490 promoted downregulation of surface CXCR4 expression on B cells from SLE patients (P=0.078 and P=0.064). Furthermore, B cells from SLE patients exhibited diminished CD63 mRNA and enhanced BCL6 mRNA expression (both P<0.05). To sum up, CXCR4 was overexpressed on SLE B cells, positively correlating with disease activity and kidney involvement. Overactivation of the PI3K/Akt and JAK/STAT pathways as well as defective CD63 synthesis may contribute to CXCR4 dysregulation in SLE.

  View details for DOI 10.1038/cmi.2016.47

  View details for PubMedID 27665947

  View details for PubMedCentralID PMC5649106

• The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nature medicine Zhang, X., Zhang, D., Jia, H., Feng, Q., Wang, D., Liang, D., Wu, X., Li, J., Tang, L., Li, Y., Lan, Z., Chen, B., Li, Y., Zhong, H., Xie, H., Jie, Z., Chen, W., Tang, S., Xu, X., Wang, X., Cai, X., Liu, S., Xia, Y., Li, J., Qiao, X., Al-Aama, J. Y., Chen, H., Wang, L., Wu, Q. J., Zhang, F., Zheng, W., Li, Y., Zhang, M., Luo, G., Xue, W., Xiao, L., Li, J., Chen, W., Xu, X., Yin, Y., Yang, H., Wang, J., Kristiansen, K., Liu, L., Li, T., Huang, Q., Li, Y., Wang, J. 2015; 21 (8): 895-905

  Abstract

  We carried out metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals with rheumatoid arthritis (RA) and healthy controls. Concordance was observed between the gut and oral microbiomes, suggesting overlap in the abundance and function of species at different body sites. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially resolved after RA treatment. Alterations in the gut, dental or saliva microbiome distinguished individuals with RA from healthy controls, were correlated with clinical measures and could be used to stratify individuals on the basis of their response to therapy. In particular, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all three sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. Molecular mimicry of human antigens related to RA was also detectable. Our results establish specific alterations in the gut and oral microbiomes in individuals with RA and suggest potential ways of using microbiome composition for prognosis and diagnosis.

  View details for DOI 10.1038/nm.3914

  View details for PubMedID 26214836

• Incidence and predictive factors for malignancies with dermatomyositis: a cohort from southern China. Clinical and experimental rheumatology Chen, D., Yuan, S., Wu, X., Li, H., Qiu, Q., Zhan, Z., Ye, Y., Lian, F., Liang, L., Xu, H., Yang, X. 2014; 32 (5): 615-21

  Abstract

  We aimed to explore the incidence of malignancy in dermatomyositis and assess the potential risk factors of occurrence of malignancy in DM from southern China.A retrospective cohort study of patients admitted in the 1st affiliated university hospital between 2003 and 2012 was performed. Demographic information, clinical symptoms, laboratory findings, medications were documented. The endpoint of the study was defined as occurrence of malignancy or death.For this approximately 10-year retrospective study, 60 out of 246 dermatomyositis patients developed malignancies with the overall incidence of 24.4%. Nasopharyngeal carcinoma (NPC) and ovarian carcinoma were the most common malignant disease, accounting for 35% (21/60) and 15% (9/60) of malignancies, respectively. Lung and colon were followed as the third most common carcinoma (5 out of 60, 8.3%). Among these 60 patients with malignancies, 39 (65.0%, 39/60) cases occurred within 1 year after DM diagnosis. Subsequently, malignancies were detected in 13 (21.7%, 13/60) patients during the second year and 8 (13.3%, 8/60) during the third year. One patient developed cancer at the 35th month after DM as the latest. The logistic regression multivariate analysis indicated that male gender [odds ratio (OR) = 3.76, 95% confidence interval (CI ) 1.86~7.61, p<0.01], dysphagia (OR= 2.21, 95%CI 1.10~4.48, p=0.03) and elevated erythrocyte sedimentation rate (ESR) (OR= 2.37, 95% CI 1.18~4.75, p=0.02) were risk factors for the occurrence of malignancies, while interstitial lung disease (ILD) acted as a protective factor (OR=0.13, 95%CI 0.06~0.28, p<0.01).It was necessary to carry out routine malignancy screening for Chinese DM patients due to its high incidence. Nasopharyngeal carcinoma and ovarian cancer were the most common malignant disease. The risk of malignancy was highest in the first year after DM diagnosis and reduced thereafter. Extensive work-ups for malignancy screening should be carried out at the first year. Male gender, dysphagia and elevated ESR were risk factors for occurrence of malignancy. The presence of ILD could diminish the risk of coexisting of malignancy.

  View details for PubMedID 25068842

• Defective PTEN regulation contributes to B cell hyperresponsiveness in systemic lupus erythematosus. Science translational medicine Wu, X. N., Ye, Y. X., Niu, J. W., Li, Y., Li, X., You, X., Chen, H., Zhao, L. D., Zeng, X. F., Zhang, F. C., Tang, F. L., He, W., Cao, X. T., Zhang, X., Lipsky, P. E. 2014; 6 (246): 246ra99

  Abstract

  PTEN regulates normal signaling through the B cell receptor (BCR). In systemic lupus erythematosus (SLE), enhanced BCR signaling contributes to increased B cell activity, but the role of PTEN in human SLE has remained unclear. We performed fluorescence-activated cell sorting analysis in B cells from SLE patients and found that all SLE B cell subsets, except for memory B cells, showed decreased expression of PTEN compared with B cells from healthy controls. Moreover, the level of PTEN expression was inversely correlated with disease activity. We then explored the mechanisms governing PTEN regulation in SLE B cells. Notably, in normal but not SLE B cells, interleukin-21 (IL-21) induced PTEN expression and suppressed Akt phosphorylation induced by anti-immunoglobulin M and CD40L stimulation. However, this deficit was not primarily at the signaling or the transcriptional level, because IL-21-induced STAT3 (signal transducer and activator of transcription 3) phosphorylation was intact and IL-21 up-regulated PTEN mRNA in SLE B cells. Therefore, we examined the expression of candidate microRNAs (miRs) that could regulate PTEN: SLE B cells were found to express increased levels of miR-7, miR-21, and miR-22. These miRs down-regulated the expression of PTEN, and IL-21 stimulation increased the expression of miR-7 and miR-22 in both normal and SLE B cells. Indeed, a miR-7 antagomir corrected PTEN-related abnormalities in SLE B cells in a manner dependent on PTEN. Therefore, defective miR-7 regulation of PTEN contributes to B cell hyperresponsiveness in SLE and could be a new target of therapeutic intervention.

  View details for DOI 10.1126/scitranslmed.3009131

  View details for PubMedID 25101889

• The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis: a meta-analysis. PloS one Lv, Q., Yin, Y., Li, X., Shan, G., Wu, X., Liang, D., Li, Y., Zhang, X. 2014; 9 (2): e89442

  Abstract

  This meta-analysis was conducted to investigate whether the status of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody are associated with the clinical response to anti-tumor necrosis factor (TNF) alpha treatment in rheumatoid arthritis (RA).A systemic literature review was performed using the MEDLINE, SCOPUS, Cochrane Library, ISI Web of Knowledge, and Clinical Trials Register databases, and Hayden's criteria of quality assessment for prognostic studies were used to evaluate all of the studies. The correlation between the RF and anti-CCP antibody status with the treatment effect of anti-TNFα agents was analyzed separately using the Mantel Haenszel method. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was applied. Publication bias was assessed using Egger's linear regression and a funnel plot.A total of 14 studies involving 5561 RA patients meeting the inclusion criteria were included. The overall analysis showed that the pooled relative risk for the predictive effects of the RF and anti-CCP antibody status on patient response to anti-TNFα agents was 0.98 (95% CI: 0.91-1.05, p=0.54) and 0.88 (95% CI: 0.76-1.03, p=0.11), respectively, with I(2) values of 43% (p=0.05) and 67% (p<0.01), respectively. Subgroup analyses of different anti-TNFα treatments (infliximab vs. etanercept vs. adalimumab vs. golimumab), response criteria (DAS28 vs. ACR20 vs. EULAR response), follow-up period (≥ 6 vs. <6 months), and ethnic group did not reveal a significant association for the status of RF and anti-CCP.Neither the RF nor anti-CCP antibody status in RA patients is associated with a clinical response to anti-TNFα treatment.

  View details for DOI 10.1371/journal.pone.0089442

  View details for PubMedID 24586782

  View details for PubMedCentralID PMC3937352

• Diagnostic value of serum anti-C1q antibodies in patients with lupus nephritis: a meta-analysis. Lupus Yin, Y., Wu, X., Shan, G., Zhang, X. 2012; 21 (10): 1088-97

  Abstract

  The autoantibodies against C1q (anti-C1q) have been reported in patients with systemic lupus erythematosus (SLE). In the past decade, though there were increasing studies suggesting it is relatively specific in lupus nephritis (LN), its overall diagnostic value in LN has not been evaluated. The meta-analysis was conducted to quantitatively evaluate the diagnostic accuracy of autoantibodies against C1q in patients with LN, and to provide more precise evidence of a correlation between anti-C1q antibodies and activity of LN. We searched Medline, Embase and Cochrane databases and contacted authors if necessary. A total of 25 studies including 2,502 patients with SLE and 1,317 with LN met our inclusion criteria for this meta-analysis. Among all 25 studies, 22 studies were available for comparison between SLE with and without LN, and 9 studies compared anti-C1q between patients with active and inactive LN. Summary receiver operating characteristic (SROC) curve was used to summarize comprehensive test performance. The QUADAS tool was used to assess the quality of the studies. For the diagnosis of LN, the pooled sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of anti-C1q were 0.58 (0.56-0.61, 95% confidence interval [95% CI]), 0.75 (0.72-0.77, 95% CI), 2.60 (2.06-3.28, 95% CI), 0.51 (0.41-0.63, 95% CI), and 6.08 (3.91-9.47, 95% CI) respectively. The area under the SROC curve (AUC) was 0.7941. For comparison between active and inactive LN, the weighted sensitivity, specificity, PLR, NLR and DOR were 0.74 (0.68-0.79, 95% CI), 0.77 (0.71-0.82, 95% CI), 2.91 (1.83-4.65, 95% CI), 0.33 (0.19-0.56, 95% CI), and 10.56 (4.56-24.46, 95% CI) respectively. The AUC was 0.8378. In conclusion, this meta-analysis indicates that anti-C1q antibodies have relatively fair sensitivity and specificity in the diagnosis of LN, suggesting that the presence of anti-C1q antibodies may be a valuable adjunct for predicting LN and assessing renal activity.

  View details for DOI 10.1177/0961203312451202

  View details for PubMedID 22777943