New-onset Systemic Lupus Erythematosus Patients Research Articles

Aberrant phenotypes of circulating γδ-T cells may be involved in the onset of systemic lupus erythematosus.

Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.

EZH2 inhibition dampens autoantibody production in lupus by restoring B cell immune tolerance.

The aim of this study was to elucidate the role of enhancer of zeste homolog 2 (EZH2) in the breakdown of B cell immune tolerance and production of autoantibodies in systemic lupus erythematosus (SLE), and to explore the therapeutic effects of EZH2 inhibition on lupus. Peripheral blood mononuclear cells (PBMCs) were collected from new-onset SLE patients for flow cytometric analysis. Pristane-induced lupus mice were constructed, and the EZH2 inhibitor was administrated by intraperitoneal injection to treat lupus mice. Blood and urine were collected from lupus mice to detect autoantibodies and proteinuria, and renal pathology scores were assessed. Mouse spleen B cells were sorted with magnetic beads and subjected to flow cytometric apoptosis detection, real time quantitative PCR (RT-qPCR), and western blotting (WB). EZH2 expression was elevated in diverse B-cell subsets in both SLE patients and pristane-induced lupus mice. The EZH2 inhibitor attenuated lupus-like symptoms and dampened autoantibody production in pristane-induced lupus mice. Inhibition of EZH2 also reduced autoantibody secretion by plasma cells from lupus patients. Mechanistically, EZH2 mediated the impaired apoptosis of autoreactive B cells and the differentiation of autoantibody producing plasma cells by inhibiting multiple cyclin-dependent kinase inhibitor (CKI) genes. EZH2 mediated the breakdown of B-cell peripheral immune tolerance by inhibiting CKI genes and participated in the generation of autoantibodies in SLE. EZH2 inhibition could serve as a promising drug intervention for the treatment of SLE.

Hsa_circ_0044235 and hsa_circ_0001947 as novel biomarkers in plasma of patients with new-onset systemic lupus erythematosus

Circular RNA (circRNA) are novel types of non-coding RNA that may be used as non-invasive noninvasive biomarkers in clinical plasma samples. However, the role of circRNA in plasma samples from patients with new-onset systemic lupus erythematosus (SLE) has not been extensively investigated. In the present study, reverse transcription-quantitative PCR was used to screen differentially-expressed circRNA (hsa_circ_0000175, hsa_circ_0044235, hsa_circ_0068367, hsa_circ_0002316, hsa_circ_0104871, hsa_circ_0001947, hsa_circ_0001481, hsa_circ_0008675, hsa_circ_0082689 and hsa_circ_0082688) in plasma samples isolated from 22 patients with new-onset SLE and 22 healthy control (HC). The results indicated hsa_circ_0000175, hsa_circ_ 0044235, hsa_circ_0068367, and hsa_circ_0001947 expression levels were significantly lower in plasma samples from new-onset SLE patients compared with corresponding levels in HC subjects and patients with new-onset rheumatoid arthritis (RA). Multivariate analysis indicated expression levels of hsa_circ_0044235 and hsa_circ_0001947 in plasma were independent risk factors for SLE. ROC curve analysis suggested that the combination of hsa_circ_0044235 and hsa_circ_0001947 indicated significant value in discriminating new-onset SLE from HC subjects and patients with RA. Moreover, the levels of hsa_circ_0044235 in plasma samples from patients with new-onset SLE were associated with platelet count, platelet-crit, and platelet distribution width; the expression of hsa_circ_0001947 in plasma from patients with SLE was associated with treatment. Thus, the present study demonstrated a promise for the combination of plasma hsa_circ_0044235 and hsa_circ_0001947 expression as potential diagnostic and prognostic biomarkers in patients with new-onset SLE.

The association of serum magnesium with infection in new-onset systemic lupus erythematosus patients.

To assess the association of serum magnesium with infection in new-onset systemic lupus erythematosus (SLE) patients. We conducted a single-center retrospective cohort study of new-onset SLE patients from 2012 to 2021. The hospitalized SLE patients were divided into infection and noninfection groups. Logistic regression analysis was conducted to examine the association of hypomagnesemia with infection. A total of 476 new-onset SLE patients were included, with 299 cases in the infection group and 177 cases in the noninfection group. The patients were mostly females (81.7%). The average age at diagnosis was 43.7years. The median duration was 1.0month. The prevalence of hypomagnesemia (<0.70), normomagnesemia (0.70-1.10), and hypermagnesemia (>1.10) in new-onset SLE patients was 14.3%, 83.4%, and 2.3%, respectively. The prevalence of hypomagnesemia was 18.4% in the infection group and 7.3% in the noninfection group (p = .001). The baseline value of serum magnesium was 0.819mmol/L, with values of 0.799mmol/L in the infection group and 0.854mmol/L in the noninfection group (p = .000). The following clinical variables were significantly different between the two groups (p < .05): age, duration, hospitalization stay, fever, serositis, and SLE Disease Activity Index 2000 (SLEDAI 2K). The laboratory parameters, including hemoglobin, white blood cell count, albumin level, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and complement C3 were also significantly different between the two groups (p < .05). The mortality was 4.4% (21/476), with 20 cases occurring in the infection group. Logistic regression analysis showed that hypomagnesemia was associated with an increased risk of infection (p = .001) and poor prognosis (p = .015). Hypermagnesemia was rare in new-onset SLE patients. Hypomagnesemia was common and was associated with an increased risk of infection in new-onset SLE patients.

The in vitro effects of vitamin 1, 25(OH) 2 D3 on expression of cytokines: In new-onset systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a variety of factors in the immune system. Awareness of the role of cytokines in SLE has led to new clinical perspectives in its pathogenesis; therefore, the aim of this study was to investigate the effect of vitamin 1, 25(OH) 2 D3 (D3) on the expression of IL-2, IL-4, IL-5, IL-10, and IFN-γ cytokines in patients with lupus. A total of 65 new-onset SLE patients were enrolled in the study. After peripheral blood mononuclear cell isolation, the lymphocytes of each patient were divided into two groups, one treated with a concentration of 50μmol vitamin D3 (test) and the other untreated with vitamin D3 (control), were cultured. After 24hours, the cultured cells were collected and the expressions of IL-2, IL-4, IL-5, IL-10, and IFN-γ genes were analyzed by RT-qPCR. It was observed that vitamin D3 reduced expression of IFN-γ, IL-4, IL-5, and IL-10 genes by 73, 50, 37, and 29%, respectively, and increased IL-2 gene expression by 31% (p ≤ 0.05). With different patterns of cytokine changes in patients with lupus in different studies, it seems that the pattern of cytokine changes is largely dependent on the phase of the disease and with this study it can be concluded that vitamin D3 administration at the time of diagnosis and in the early stages and before starting treatment have different effects from its administration in the acute stage of the disease, which requires further studies to prove. It seems that in patients with systemic lupus erythematosus, vitamin D should be administered taking into account the phase of the disease.

Uncoupled bone remodeling is characteristic of bone damage in premenopausal women with new-onset systemic lupus erythematosus.

To investigate the mechanism underlying systemic lupus erythematosus (SLE)-related bone loss by evaluating the bone mineral density (BMD) and bone turnover markers (BTMs) in premenopausal patients with new-onset SLE without any treatment. BMD and BTMs of 106 premenopausal patients with new-onset SLE and 64 gender-, age- and body mass index (BMI)-matched healthy controls were analyzed. BMD was determined using dual energy X-ray absorptiometry (DXA). Serum BTMs were measured. Hip and lumbar spine BMD in premenopausal patients with new-onset SLE was significantly decreased compared with healthy controls. Higher rate of osteoporosis was observed in new-onset SLE patients (25% vs. 1%). Moreover, uncoupled bone remodeling evidenced by an increase in bone resorption marker β-CTX (685.9 ± 709.6 pg/mL vs. 395.4 ± 326.0 pg/mL, P < 0.05) and decrease in bone formation markers PINP (37.4 ± 33.0 ng/mL vs. 46.1 ± 20.9 ng/mL, P < 0.05) and OC (11.4 ± 9.8 ng/mL vs. 18.2 ± 8.6 ng/mL, P < 0.05) was observed in premenopausal patients with new-onset SLE compared with healthy controls. Univariate correlation analyses showed negative correlations between OC and SLE Disease Activity Index (SLEDAI), and positive correlations between β-CTX and SLEDAI. SLE patients positive for dsDNA, nucleosome showed lower OC and higher β-CTX. Premenopausal patients with new-onset SLE had decreased BMD and abnormal bone metabolism with increased β-CTX and decreased OC and P1NP levels, indicating uncoupled bone remodeling in new-onset SLE patients. Disease activity and abnormal immunity, especially the amount of antibodies in SLE patients, were strongly associated with abnormality of bone metabolism.

Layer-specific strain and dyssynchrony index alteration in new-onset systemic lupus erythematosus patients without cardiac symptoms.

Layer-specific speckle-tracking echocardiography (STE) is a noninvasive approach that assesses subclinical left ventricular dysfunction. We aimed to investigate the (I) alteration of layer-specific STE parameters and the dyssynchrony index; and (II) the disease parameters associated with layer-specific STE change in drug-naïve patients with new-onset systemic lupus erythematosus (SLE) without cardiac symptoms. Thirty-five drug-naïve patients with new-onset SLE and twenty-five healthy controls were enrolled. All individuals received both conventional echocardiographic and two-dimensional STE assessment. The data of layer-specific global longitudinal strain (GLS), global circumferential strain (GCS), and peak systolic dispersion (PSD) were acquired in layer-specific STE. All patients had a normal left ventricular ejection fraction (LVEF)(mean LVEF: 58%) and conventional echocardiographic parameters were comparable between patients and controls. Decreased layer-specific GLS and elevated PSD were observed in SLE patients (whole layer GLS: -17.6%±3.0% versus -19.3%±2.6%, P=0.02; endocardial GLS: -20.0%±3.2% versus -22.1%±3.0%, P=0.01; epicardial GLS: -15.6%±2.7% versus -16.8%±2.4%, P=0.04; PSD: 41.0±18.9 versus 28.8±10.1 msec, P=0.007). In contrast, there was no difference in layer-specific GCS at three different levels between patients and controls (P>0.05). More severely impaired GLS was observed in patients with higher disease activity, high-risk antiphospholipid antibody (aPL) profile, or renal involvement. The PSD was increased in patients with higher disease activity or a high-risk aPL profile. Correlational analysis showed that GLS at three layers and PSD correlated with high-sensitivity C-reactive protein (hsCRP) levels (whole GLS: r=0.662, P<0.001; endocardial GLS: r=0.637, P<0.001; epicardial GLS: r=0.658, P<0.001; PSD: r=0.390, P=0.021). PSD correlated with epicardial GLS (r=0.360, P=0.047), when treating the hsCRP level, renal involvement, aPL profile, and disease activity as control variables. Multivariate regression showed the hsCRP level and epicardial GLS were predictors of layer-specific GLS impairment and elevated PSD, respectively. Drug-naive patients with new-onset SLE are likely to have subclinical GLS impairment and left ventricular dyssynchrony, even in the presence of normal LVEF. SLE-related risk factors are associated with these dysfunctions.

Multimorbidity among incident Finnish systemic lupus erythematosus patients during 2000-2017.

The objective of the study was to examine the risk of other morbidities among patients with systemic lupus erythematosus (SLE). A total of 1006 adult new-onset SLE patients were identified during 1.1.2000- 31.12.2014 from the register of Social Insurance Institution. For each case three general population controls matched according to age, sex and place of residence at the index day were sampled from the population register. Both groups were followed up from the index date until the end of 2017 or until death. The national register on specialized care was explored to gather broadly their 12 organ-specific morbidities, which were found among 91.2% of SLE patients and 66.7% of comparators. The rate ratio (RR) was elevated in almost all disease groups. Musculoskeletal, cardiovascular and genitourinary conditions were the most common comorbidities with RRs of 1.82 (1.68 to 1.97), 1.91 (1.76 to 2.08) and 1.91 (1.73 to 2.09), respectively. Men with SLE had a significantly higher risk for diseases of the genitourinary system and endocrine, nutritional and metabolic diseases compared to women with SLE. The risk of concurrent morbidities is essential to note in the care of SLE patients.

Clinical features of new-onset systemic lupus erythematosus during pregnancy in Central China: a retrospective study of 68 pregnancies.

The aim of this study is to explore the clinical features and pregnancy outcomes of Chinese patients with new-onset systemic lupus erythematosus (SLE) during pregnancy or puerperium. We retrospectively evaluated the data of all pregnant women with SLE managed at the First Affiliated Hospital of Zhengzhou University between April 2013 and March 2017. Clinical characteristics, laboratory features, medication use, and pregnancy outcomes were compared between pregnant women with new-onset SLE and pregnant women with pre-existing SLE. Risk factors for adverse pregnancy outcomes were determined using binary regression analyses. Overall, 223 pregnancies in 216 patients were included; 148 (69.6%) patients had a history of SLE, and 68 (30.4%) were diagnosed with SLE during pregnancy or puerperium. Most cases of new-onset SLE (72.1%) occurred during the first and second trimesters. Thrombocytopaenia (especially severe thrombocytopaenia) (76.5% vs 54.2%, P = 0.008; 39.7% vs 15.5%, P = 0.001) and anaemia (especially moderate anaemia) (73.5% vs 56.9%, P = 0.007; 52.9% vs 35.2%, P = 0.035) were more common in women with new-onset SLE than in women with pre-existing SLE and active disease during pregnancy. Additionally, patients with new-onset SLE experienced higher rates of moderate-to-severe disease activity than patients with pre-existing SLE (P < 0.01); disease activity occurred mostly during the first and second trimesters (75.4%). Compared with pre-existing SLE patients, disease activity in new-onset SLE patients occurred mostly in the first trimester (33.3% vs 15.3%, P = 0.043) and less in the third trimester (21.1% vs 47.2%, P < 0.001). Pregnancy loss was significantly higher in patients with new-onset SLE than in patients with pre-existing SLE (62.4% vs 27.1%, P < 0.001), with most cases occurring during the first and second trimesters (95.3%). However, there were no significant differences in neonatal outcomes between new-onset and pre-existing SLE patients with active disease. Within the new-onset SLE group, active disease was an independent risk factor for pregnancy loss (odds ratio [OR] = 16.185, confidence interval [CI] = 1.895-138.232, P = 0.011), whereas disease onset at late gestation was a protective factor against pregnancy loss (OR = 0.589, CI = 0.435-0.796, P = 0.013). Patients with new-onset SLE suffered greater haematological involvement (mainly thrombocytopaenia and anaemia) and higher rates of moderate-to-severe disease activity and pregnancy loss than patients with pre-existing SLE. Controlling disease activity and extending gestational age may improve pregnancy outcomes in women with new-onset SLE. Key Points • The clinical features of new-onset SLE during pregnancy and its impact on pregnancy outcomes have rarely been reported, especially in Chinese patients. • New-onset SLE during pregnancy in Chinese women occurred primarily during the first and second trimesters and was characterised by haematological disorders, including thrombocytopaenia and anaemia. • Women with new-onset SLE during pregnancy had significantly higher disease activity scores and pregnancy loss rates than women with pre-existing SLE, especially during the first and second trimesters; controlling disease activity and prolonging gestational age may improve pregnancy outcomes in this setting.

RNA-seq of circular RNAs identified circPTPN22 as a potential new activity indicator in systemic lupus erythematosus

Circular RNAs (circRNAs) are possible biomarkers for many diseases, but the knowledge of circRNAs in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) remains limited. This study aimed to assess the expression of circRNAs in PBMCs from patients with SLE and healthy individuals by RNA sequencing (RNA-seq). In total, 128 circRNAs were significantly differentially expressed including 39 upregulated and 89 downregulated circRNAs in four new-onset SLE patients compared with three healthy controls. After verification of the four candidate circRNAs in 49 patients with SLE and 37 controls using quantitative real-time polymerase chain reaction (qRT-PCR) assays, a previously undescribed circRNA with potential translation activity, circPTPN22, was selected to confirm its clinical significance. Bioinformatics analysis demonstrated that the parent gene of circPTPN22 was protein tyrosine phosphatase non-receptor type 22 (PTPN22), a potent regulator of T cell activation. The downregulation of circPTPN22 in patients with SLE was strongly negatively correlated with their Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores. circRNA-miRNA-mRNA co-expression network analysis indicated a correlation between circPTPN22 and the miRNAs and mRNAs related to immunological regulation including the development of SLE. Patients with higher SLEDAI scores had lower circPTPN22 expression levels, and long-term hormone treatment significantly increased circPTPN22 levels. Receiver operating characteristic curve analysis indicated that circPTPN22 has good diagnostic value for SLE. Our data demonstrated the aberrant expression of circRNAs in patients with SLE compared with healthy controls; circPTPN22 might function as a diagnostic and disease severity indicator in SLE.

Altered frequency of Th17 and Treg cells in new‐onset systemic lupus erythematosus patients

T helper 17 (Th17) and regulatory T (Treg) cells play an important role in pathogenesis of systemic lupus erythematosus (SLE). Their imbalance was reported in treated SLE patients, while very little is known about the relationship between Th17 and Treg cells in new-onset untreated SLE patients. To assess the role of Th17/Treg cells in the pathogenesis of new-onset SLE. Thirty-nine new-onset SLE patients and 33 age-matched healthy adults were enrolled. We analysed Th17 and Treg cells in different level, including their frequencies in peripheral blood mononuclear cell, the expression of interleukin-17 A (IL-17A) and forkhead box P3 (FoxP3) proteins, the expression of retinoid-related orphan nuclear receptor γt (RORγt) and FoxP3 genes and plasma level of IL-17A. The frequency of Th17 and Treg cells, the expression of IL-17A among Th17 cell, the plasma level of IL-17A, the expression of RORγt and FoxP3 genes were all significantly higher in SLE patients. Th17 cells were negatively correlated with Treg cells. We also found that plasma level of IL-17A was positively correlated with SLE disease activities index (SLEDAI) scores and an equation among the level of C3, IgA, IL-17A and SLEDAI scores. Results indicate that Th17 and Treg cells take roles in the pathogenesis of SLE. Th17 cells might suppress the differentiation of Treg cells, and feedback effects might exist between them during SLE pathogenesis. The measure of plasma level of IL-17A may be useful for evaluation of disease activity in new-onset SLE patients.

Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients.

A hallmark of systemic lupus erythematosus (SLE) is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies; however, the antibody-independent features of the B-cell compartment in SLE are less understood. In this study, we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients. We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients. Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner, which can be recapitulated by direct IFN-α treatment. Furthermore, the effect of IFN-α on enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax. Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6, which was also linked to the overactivated type I IFN pathway. In addition, the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients, and these cells were significantly reduced after short-term standard therapies. Thus, the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients, which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.

Clinical features of new-onset systemic lupus erythematosus in pregnant patients.

This study was conducted to examine the clinical characteristics of new-onset systemic lupus erythematosus (SLE) during pregnancy. We performed a retrospective study of all pregnancies in patients with SLE managed at The People's Hospital of Peking University from 2008 to 2015. In total, 97 pregnancies were identified and studied, 22 of which were first diagnosed with SLE during pregnancy or puerperium. New-onset SLE mainly occurred during the first and second pregnancy trimesters. Blood and multi-organ involvement were detected in 95.45% and 45.45% of new-onset patients, respectively, and both had a higher incidence than in active patients. Thrombocytopenia was the most common blood involvement in new-onset patients. All three maternal deaths occurred in new-onset patients. There were nine (40.91%) fetal losses, three (13.64%) low birth weight infants, one (4.54%) fetal malformation and two (9.09%) cases of neonatal lupus in new-onset patients. New-onset pregnant SLE patients were characterized with blood system involvement and generally experienced more adverse maternal outcomes than active patients with SLE history. However, adverse fetal outcomes in new-onset patients were the same as those of active patients with an SLE history.

Altered frequencies of memory B cells in new-onset systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease, characterized by B cell hyperactivity and pathogenic autoantibodies formation. The objective of this study is to evaluate the distribution of B cell subsets in patients with SLE. We included patients with SLE followed in First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, China. Flow cytometry was used to measure frequencies of B cell subsets, including memory B cells, switched memory B cells, non-switched memory B cells, double-negative memory B cells, and naïve B cells in 130 patients with SLE and 55 healthy controls. The different distributions of B cell subsets were further evaluated by their associations with disease activity and clinical manifestation. SLE patients showed significant alteration of B cell subsets, including lower frequency of non-switched memory B cells and higher double-negative memory B cells. The frequencies of B cell subsets also varied between new-onset SLE patients and chronic SLE patients. Frequencies of total memory B cells, switched memory B cells, and non-switched memory B cells were lower in new-onset SLE patients and frequency of naïve B cells was higher compared with healthy controls. Chronic SLE patients showed increased switched memory B cells and double-negative memory B cells. In addition, switched memory B cells and double-negative B cells were higher in patients with lupus nephritis (LN) regardless of disease activity. Our findings suggested that abnormalities of the B cell subsets homeostasis might contribute to the pathogenesis of SLE.

Anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus.

BackgroundThe clinical significance of anti-neutrophil cytoplasmic antibodies in patients with new-onset systemic lupus erythematosus, especially in systemic disease accompanied by interstitial lung disease remains to be elucidated.ObjectivesThis study was designed to investigate the role of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients.MethodsA hundred and seven patients with new-onset SLE were enrolled. Presence of anti-neutrophil cytoplasmic antibodies in the sera was assessed by indirect immunofluorescence as well as enzyme linked immunosorbent assay against proteinase-3 and myeloperoxidase. Clinical features and laboratory parameters of patients were also recorded. All patients were subjected to chest X-ray, chest high-resolution computed tomography and pulmonary function test.ResultsForty-five systemic lupus erythematosus patients (45/107, 42%) were seropositive for anti-neutrophil cytoplasmic antibodies. Compared with anti-neutrophil cytoplasmic antibodies-negative patients, the anti-neutrophil cytoplasmic antibodies-positive patients had significantly higher incidence of renal involvement, anemia, and Raynaud's phenomenon as well as decreased serum level of complement 3/complement 4 and elevated erythrocyte sedimentation rate. In addition, there was a positive correlation between serum anti-neutrophil cytoplasmic antibodies level and disease activity of systemic lupus erythematosus. Furthermore, prevalence of interstitial lung disease in the anti-neutrophil cytoplasmic antibodies -positive patients (25/45, 55.6%) was obviously higher than that in the anti-neutrophil cytoplasmic antibodies-negative patients (15/62, 24.2%).Study limitationsThe sample size was limited and the criteria for screening new-onset systemic lupus erythematosus patients might produce bias.ConclusionsThe level of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients correlates positively with the disease activity and the prevalence of interstitial lung disease.

Elevated serum autoantibodies against co-inhibitory PD-1 facilitate T cell proliferation and correlate with disease activity in new-onset systemic lupus erythematosus patients

BackgroundProgrammed cell death protein 1 (PD-1) plays an important role in immune response regulation as a co-inhibitory signal during T cell activation. However, there is little known about the serum autoantibody profile of PD-1 in systemic lupus erythematosus (SLE), a disease characterized by the breakdown of immune tolerance to self-antigens and an excessive production of autoantibodies. Thus, we aim to investigate the serum levels and function of anti-PD-1 in patients with new-onset SLE.MethodsSerum levels of anti-PD-1 IgG and IgM isotypes were detected in new-onset SLE patients (n = 90), rheumatoid arthritis (n = 50), primary Sjogren’s syndrome (n = 50), ankylosing spondylitis (n = 25), and healthy controls (HC) (n = 80) using an enzyme-linked immunosorbent assay (ELISA). The correlation of anti-PD-1 with clinical characteristics and laboratory parameters of patients with new-onset SLE was analyzed. The effects of purified anti-PD-1 IgG from SLE patients on T cell proliferation were measured using flow cytometry.ResultsThe data revealed increased levels of anti-PD-1 IgG, but not IgM, especially in new-onset SLE patients, and the positive rate of anti-PD-1 IgG was 30 (33.3%). The level of anti-PD-1 IgG was closely associated with malar rash (OR = 15.773), arthritis (OR = 22.937), serositis (OR = 16.008), hematological (OR = 35.187), renal (OR = 8.306), and neurological involvement (OR = 37.282). Moreover, the serum levels of anti-PD-1 IgG were positively correlated with the SLE disease activity index (SLEDAI) score (r = 0.296, p = 0.0046) and the erythrocyte sedimentation rate (ESR) (r = 0.2446, p = 0.0201). In vitro examination showed that purified anti-PD-1 IgG obtained from SLE patients enhanced T cell proliferation when co-cultured with dendritic cells (DCs).ConclusionsThe current study indicates, for the first time, that the serum levels of co-inhibitor autoantibodies against PD-1 are elevated in new-onset SLE patients and are associated with disease activity in SLE. Autoantibodies against PD-1, facilitating T cell proliferation, revealed a new insight into the function of negative regulation signals involved in the pathogenesis of SLE.

Effect of serum interleukin-21 on B cell secretory capacity and apoptosis in patients with systemic lupus erythematosus

Objective: To investigate the secretory capacity and apoptosis of interleukin (IL)-21 induced normal B cells by co-culture with serum from patients with systemic lupus erythematosus (SLE). Methods: Serum from twenty new-onset SLE patients and 20 healthy donors were collected. CD(19)(+) B cells from the normal controls were co-cultured with serum from SLE patients in the presence or absence of IL-21-R-FC(4 μg/ml). Supernatant IgG and IgM concentration were measured by immunoturbidimetric assay on day 5. Supernatant anti-dsDNA level was determined by ELISA. The percentage of apoptotic cells was detected by flow cytometer. Results: IgG, IgM and anti-dsDNA levels in normal B cells with SLE serum were significantly higher than those in the serum of SLE patients alone [(5.84±1.79)g/L vs (4.25±1.48)g/L, P=0.000; (0.46±0.21)g/L vs (0.43±0.21)g/L, P=0.003; (127.76±70.24)IU/ml vs (115.15±63.88) IU/ml, P=0.014 respectively]. However, no significant differences were found in the group of normal B cells with non-homologous serum from normal controls (P>0.05). Supernatant IgG, IgM and anti-dsDNA levels in normal B cells with SLE serum significantly decreased while IL-21R-fusion protein was added [(5.26±1.62)g/L vs (5.84±1.79)g/L, P=0.006; (0.42±0.20)g/L vs (0.46±0.21)g/L, P=0.002; (118.00±69.62)IU/ml vs (127.76±70.24)IU/ml, P=0.012 respectively]. The apoptotic rate of B cells with SLE serum was significantly higher than that with normal serum [(47.88±12.65)% vs (38.86±10.32)%, P=0.004]. But adding IL-21R-fusion conversed the apoptotic rates [(42.08±12.52)% vs (47.88±12.65)%, P=0.001]. Conclusions: SLE serum could induce normal B cells to form immunoglobulin secreting cells and producing autoantibodies, or apoptosis in pathological conditions. IL-21 might be considered as a potential therapeutic target of SLE.

Association of P2X7R Functional Expression and Gene Polymorphisms with Systemic Lupus Erythematosus

Objective: To investigate P2X purinoceptor 7 (P2X7R) expression changes on peripheral blood mononuclear cell (PBMC) surfaces of systemic lupus erythematosus (SLE) patients as well as their association with serum cytokine levels and patients’ clinical features. In addition, the effects of different P2X7R single nucleotide polymorphisms (SNPs) on P2X7R expression and cytokine production were investigated. Method: Twenty-nine new-onset SLE patients and twenty-eight healthy controls were enrolled, while P2X7R expression levels of lymphocytes, CD4+ cells and CD19+ cells were analyzed by flow cytometry. Serum IL-1β, IL-6 and TNF-α levels were analyzed by ELISA and three P2X7R SNPs (1068G>A, 1096C>G and 1513A>C) were PCR genotyped in 14 SLE patients and 14 healthy controls. Results: P2X7R surface expression levels of lymphocytes, CD4+ and CD19+ cells from new-onset SLE patients were significantly higher than that of controls and significantly elevated on lymphocytes from patients with concurrent arthritis or leukopenia as well as on CD19+ cells of NP-SLE patients. Moreover, P2X7R expression levels on lymphocytes and CD19+ cells of SLE patients were positively correlated with serum TNF-α/IL-6 and TNF-α level, respectively. SLE patients with the P2X7R 1068GG genotype had significantly higher expression level ratios of TNF-α, IL-6 and IL-1β to P2X7R on lymphocytes compared to patients harboring the 1068GA genotype. Conclusion: P2X7R, as an important cell surface regulator of several key cytokines, is involved in the pathogenesis of SLE and also associated with organ injuries like arthritis, leukopenia and neuropsychiatric damage. P2X7R 1068GG maybe a SLE susceptibility genotype since it enhances cytokine secretion in SLE patients.

Dynamic changes in the numbers of different subsets of peripheral blood NK cells in patients with systemic lupus erythematosus following classic therapy.

Imbalance of natural killer (NK) cells is associated with the development of systemic lupus erythematosus (SLE). However, little is known about the dynamic changes on NK cells following therapy. This study aimed at examining the impact of classic therapies on the numbers of different subsets of NK cells in new-onset SLE patients. The numbers of different subsets of peripheral blood NK cells in 24 new-onset SLE patients before, 4 and 12weeks post the classic therapies, and 7 healthy controls were determined by flow cytometry. The potential correlation between the numbers of NK cells and the values of clinical measures was analyzed. In comparison with that before treatment, the numbers of NK, NKG2C+, and KIR2DL3+ NK cells were significantly increased while the numbers of NKp46+ and NKG2A + NK cells significantly decreased at 4 and/or 12weeks post the treatment only in the drug well-responding patients, but not in those poor responders (P < 0.05 for all). The numbers of NKG2C + NK cells were correlated positively with the levels of serum C3 while the numbers of KIR2DL3+ NK cells were correlated negatively with the scores of SLEDAI in these patients at 4weeks post the treatment. The classic therapies modulated the numbers of some subsets of NK cells in drug well-responding SLE patients. The changes in the numbers of some subsets of NK cells may serve as biomarkers for evaluating the therapeutic responses of SLE.

Detection of dynamic frequencies of Th17 cells and their associations with clinical parameters in patients with systemic lupus erythematosus receiving standard therapy.

Recent evidence implicated an important role of Th17 cells in the pathogenesis of systemic lupus erythematosus (SLE). However, the association between dynamic changes of Th17 cell frequency and clinical parameters in SLE patients receiving clinical managements remains unknown. Here, we sought to evaluate their correlation in Chinese new-onset SLE patients with standard therapy. We found that the frequency of Th17 cells was higher in SLE patients than that in healthy controls and could be decreased by standard care. In consistent, the level of serum IL-6, IL-1β, IL-23, and Stat3 activity was elevated in SLE patients and down-regulated by disease treatment. Of note, the frequency of Th17 cells was correlated with SLEDAI and serum C3 in SLE patients. The changes of Th17 cell frequency were associated with those of SLEDAI and serum C3 in SLE patients between pretreatment and posttreatment. Further, the Th17 cell frequency was positively correlated with serum anti-dsDNA antibody in SLE patients. The changes of Th17 cell frequency were associated with those of serum anti-dsDNA antibody in SLE patients. Our findings showed that dynamic frequencies of Th17 cells were closely correlated with clinical parameters in SLE patients receiving standard treatment, which could facilitate the efficient management and development of novel therapeutics for SLE.