New-onset Systemic Lupus Erythematosus Research Articles

Life threatening pericardial and neurologic presentations in systemic lupus erythematosus

Background: Posterior reversible encephalopathy syndrome (PRES) is characterized by altered mental status, visual perception abnormalities and seizures. Systemic lupus erythematosus (SLE) is a rare etiology of PRES and affects less than 1% of SLE patients. We present a unique case of a new-onset SLE patient presenting with borderline cardiac tamponade requiring emergent pericardiocentesis and hospital course complicated by intractable seizures found to have PRES on imaging.Case presentation: A 21-year-old female underwent outpatient evaluation for new-onset SLE presenting to the emergency room with dyspnea. She was found to have a large circumferential pericardial effusion with borderline tamponade features requiring emergent pericardiocentesis. On her fifth hospital day, she developed generalized motor seizure (tonic-clonic) with magnetic resonance imaging (MRI) revealing bilateral parieto-occipital edema consistent with a radiographic diagnosis of PRES. Induction therapy with mycophenolate was started and follow-up studies showed improvement in the cortical and subcortical regions on MRI with no evidence of recurrent pericardial effusion.Conclusions: PRES is a rare complication of lupus and has been infrequently described in literature. It is thought that the association is secondary to the effect of SLE on endothelial dysfunction and the effect of cytotoxic medication on the loss of autoregulation of systemic hypertension. It is important to recognize this condition and its significant associations as early detection and intervention often lead to favorable outcomes. To our knowledge, this is the first case report of SLE with associations of both PRES and circumferential pericardial effusion with tamponade physiology, both of which are rare in the SLE patient population.

Use of echocardiography at diagnosis and detection of acute cardiac disease in youth with systemic lupus erythematosus.

Objectives There are no guidelines on the use of echocardiography to detect cardiac manifestations of childhood-onset systemic lupus erythematosus (SLE). We quantify the prevalence of acute cardiac disease in youth with SLE, describe echocardiogram utilization at SLE diagnosis, and compare regional echocardiogram use with incident cardiac diagnoses. Methods Using the Clinformatics® DataMart (OptumInsight, Eden Prairie, MN) de-identified United States administrative database from 2000 to 2013, we identified youth ages 5-24 years with new-onset SLE (≥3 ICD-9 SLE codes 710.0, > 30 days apart) and determined the prevalence of diagnostic codes for pericardial disease, myocarditis, endocarditis, and valvular insufficiency. Multiple logistic regression was used to identify factors associated with echocardiography during the baseline period, up to one year before or six months after SLE diagnosis. We calculated a regional echocardiogram utilization index, which is the ratio of observed use over the mean predicted probability based on all available baseline characteristics. Spearman's rank correlation coefficient was used to evaluate the association between regional echocardiogram utilization indices and percentage of imaged youth diagnosed with their first cardiac manifestation following echocardiography. Results Among 699 youth with new-onset SLE, 18% had ≥ 1 diagnosis code for acute cardiac disease, of which valvular insufficiency and pericarditis were most common. Twenty-five percent of all youth underwent echocardiogram during the baseline period. Regional echocardiogram use was positively correlated with the percentage of imaged youth found to have cardiac disease (ρ = 0.71, p = 0.05). There was up to a five-fold difference in adjusted odds of baseline echocardiography between low- and high-utilizing regions (OR = 0.19, p = 0.007). Conclusion Nearly one-fifth of youth with new-onset SLE have acute cardiac manifestations; however, use of echocardiograms at SLE diagnosis is highly variable. There may be incremental diagnostic value to early use of echocardiography, but prospective studies are needed to determine whether greater use of echocardiograms modifies outcomes.

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.

Systemic lupus erythematosus (SLE): an unusual cause of ileocolic intussusception

Intussusception is a rare diagnosis in adults. Gastrointestinal involvement is not unusual in systemic lupus erythematosus (SLE).1 A case of intussusception as first presenting symptom of SLE is described. A...

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.

Increased risk of systemic lupus erythematosus in pregnancy-induced hypertension: A nationwide population-based retrospective cohort study.

Dysregulation of the immune system plays a role in the pathogenesis of both, pregnancy-induced hypertension (PIH) and systemic lupus erythematosus (SLE). It is well known that SLE predisposes to be complicated with PIH. However, few studies have attempted to investigate whether PIH increased subsequent SLE risk.The objectives of this study were to assess the association between PIH and subsequent SLE risk and identify predictive risk factors.Patients with newly diagnosed PIH were selected from the Taiwan National Health Insurance Research Database (NHIRD) and compared with a matched cohort without PIH based on age and the year of delivery. The incidence of new-onset SLE was evaluated in both cohorts. The overall observational period was from January 1, 2000 to December 31, 2013.Among the 23.3 million individuals registered in the NHIRD, 29,091 patients with PIH and 116,364 matched controls were identified. The incidence of SLE was higher among patients with PIH than in the matched controls (incidence rate ratio [IRR] = 4.02, 95% confidence interval [CI] 3.98–4.05, P < 0.0001). The IRR for subsequent SLE development remained significantly higher in all stratifications during the follow-up years. The multivariate Cox regression model was performed and the results showed that PIH may be an independent risk factors for the development of subsequent SLE (hazard ratio [HR] = 2.87, 95% CI 2.07–3.98, P < 0.0001). Moreover, multivariate Cox regression model was used again among the PIH cohort only in order to identify the possible risk factors for subsequent SLE in the population with PIH.Patients with PIH may have higher risk of developing newly diagnosed SLE than those without PIH. In addition, among individuals who have experienced PIH, those younger than 30 years, having experienced preeclampsia/eclampsia, single parity, preterm birth, or chronic kidney disease, may display an increased subsequent risk 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.

New-onset systemic lupus erythematosus in a long-term hemodialysis patient with acute pleuritis and pneumonitis.

A 61-year-old woman, with a 25-year history of maintenance hemodialysis due to end-stage renal disease of unknown causes, was admitted because of systemic joint pain and inflammatory response of unknown etiology that persisted for 1month. Laboratory data on admission revealed leukocytopenia, lymphocytopenia, high serum C-reactive protein, and positivity for antinuclear antibody (ANA) and anti-double strand DNA. After admission, she progressively developed cough and dyspnea. A chest radiograph revealed bilateral ground glass opacity and pleural effusion. A thoracentesis revealed lupus erythematosus cells, suggesting lupus pleuritis. A chest computed tomography showed a pattern of diffuse alveolar damage compatible with acute lupus pneumonitis. She fulfilled the American Rheumatism Association diagnostic criteria for systemic lupus erythematosus (SLE). Methylprednisolone pulse therapy followed by oral prednisone treatment improved the clinical symptoms and laboratory abnormalities. ANA was negative 25years earlier when she first started hemodialysis and she had neither clinical nor serological abnormalities related to SLE during the last 25years. Further, she had neither received drugs that can cause drug-induced SLE, nor had a history of ultraviolet ray exposure, pregnancy, blood transfusion, trauma and smoking. This report suggests that new-onset SLE can develop in patients undergoing long-term dialysis. Hence, when we encounter dialysis patients with arthralgia and/or respiratory disorders, we should consider the possibility of new-onset SLE.

Increased interleukin 21 and follicular helper T-like cells and reduced interleukin 10+ B cells in patients with new-onset systemic lupus erythematosus.

To elucidate the potential role of follicular helper T cells (TFH) and interleukin 10 (IL-10)+ B cells in the development of systemic lupus erythematosus (SLE). The numbers of peripheral blood CD27+, CD38+, CD86+, CD95+, IL-10+ B cells, and inducible T cell costimulator (ICOS)+, programmed death-1 (PD-1)+, IL-21+, CXCR5+CD4+ TFH-like cells were examined in 23 patients with new onset SLE and 20 healthy controls (HC). In comparison with HC, significantly reduced numbers of CD19+ and IL-10+ B cells, but increased numbers of CD27(high), CD86+, CD95+ B cells, CXCR5+CD4+, ICOS+, PD-1+, and IL-21+ TFH-like cells were detected, which were accompanied by higher levels of serum IL-21, but lower levels of IL-10 in the patients. Treatment with anti-SLE therapy modulated the imbalance of different subsets of B and TFH-like cells. The levels of serum IL-21 and IL-10 were positively correlated with the numbers of CD4+CXCR5+ TFH-like and CD19+CD5+CD1d+ B cells in the patients, respectively. The numbers of CD27(high) B cells were correlated positively with IL-21+ TFH-like cells, but negatively with IL-10+ B cells. The values of SLE Disease Activity Index, C3, and erythrocyte sedimentation rate were correlated positively with serum IL-21, but negatively with IL-10 in those patients. Our data indicate that the imbalance of IL-21+ TFH-like, CD27(high), and IL-10+ B cells may be associated with the pathogenesis of SLE, and levels of serum IL-21 and IL-10 may be valuable for evaluating disease activity in SLE.

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.

AB0180 Plasma IL-22 Levels Correlate with Th22 Cells in Patients with New-Onset Systemic Lupus Erythematosus

BackgroundRecently, there is emerging evidence that IL-22 and IL-22-producing Th cells are involved in the pathogenesis of autoimmune diseases. The roles of IL-22 and IL-22-producing Th cells in SLE remain...

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.

Clinical Relevance of Plasma miR‐21 in New‐Onset Systemic Lupus Erythematosus Patients

Plasma miR-21 is widely investigated as biomarker in many diseases. Recent studies show that miR-21 participates in the development of systemic lupus erythematosus (SLE). The aim of this study was to evaluate the expression profile of miR-21 in the plasma of SLE patients. Relative quantities of plasma miR-21 both in SLE patients and healthy controls were determined by relative qRT-PCR under endogenous and exogenous controls. The diagnostic value of plasma miR-21 was evaluated in SLE patients. Data of some SLE-associated clinical parameters were collected. Eighty participants from Central China were recruited. Forty-four participants were new-onset SLE patients and the others were healthy controls. Plasma miR-21 level in SLE patients was higher than that of healthy controls (P = 0.031). Receiver operating characteristic analysis of plasma miR-21 revealed an Area Under Curve (AUC) of 0.64 ± 0.06 (95% CI: 0.51-0.76, P = 0.03854) when differentiating SLE from healthy controls. The level of plasma miR-21 was not associated with the level of white blood cells (P = 0.4284), red blood cells (P = 0.4079), and platelets (P = 0.4961), but significantly correlated with the level of plasma complement C3 (r = -0.5297, P = 0.0004), C4 (r = -0.4732, P = 0.0020), and serum uric acid (r = 0.3932, P = 0.0121) in SLE patients. Plasma miR-21 in SLE patients from Central China is overexpressed. Since circulating miR-21 is aberrantly expressed in many diseases, the applying of it as a disease biomarker should be considered carefully.

Differential expression of natural killer activating and inhibitory receptors in patients with newly diagnosed systemic lupus erythematosus

Systemic lupus erythematosus (SLE) presents as the abnormal activation and over-proliferation of immune competent cells. Few studies have characterized the role of natural killer (NK) and NK T (NKT) cells in the pathogenesis of SLE, and therefore a consensus has not been reached as yet. Thirty-two patients with new-onset SLE and 15 healthy controls were recruited. Activated and inhibitory NK and NKT cells in peripheral blood were quantified by flow cytometry. The proportions of spontaneous and stimulated interferon (IFN)-γ(+) NK and NKT cells and CD107a(+) NK cells was examined. Finally, the potential relationship between the cell subsets and clinical indexes was analyzed. The proportions of NK and NKT cells (P=0.002 and 0.004, respectively) as well as the proportions of NKG2C(+) NK cells, inhibitory NK and NKT cell subsets (P=0.016, P=0.019, P=0.049, and P=0.028, respectively) in SLE patients were significantly lower than those in controls. In contrast, the proportions of activated NK cells and NKT cell subsets were significantly higher (P=0.036, P=0.034, P=0.005, and P=0.007, respectively). Moreover, the proportions of stimulated IFN-γ(+) NKT cells were significantly higher than in the controls, and the proportions of stimulated CD107a(+) NKT cells in SLE patients were significantly lower than in the controls (P=0.032 and P=0.02, respectively). Lower proportions of NK and NKT cells, higher proportions of activated NK cells and activated NKT cells, lower proportions of inhibitory NK and NKT cells, higher NKT cell activity, and lower NKT cell degranulation may induce the autoimmune reaction involved in the pathogenesis of SLE.

Decreased Plasma IL‐22 Levels and Correlations with IL‐22‐Producing T Helper Cells in Patients with New‐Onset Systemic Lupus Erythematosus

Interleukin-22 (IL-22) and IL-22-producing T helper (Th) cells are involved in the pathogenesis of autoimmune diseases. However, the roles of IL-22 and IL-22-producing T helper cells in systemic lupus erythematosus (SLE) remain unclear. Plasma levels of IL-22 were measured in 41 patients with SLE (19 new-onset and 22 relapsing patients) and 20 healthy controls by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the percentages of CD4(+) IFN-γ(+) (Th1), CD4(+) IL-17(+) (Th17) and CD4(+) IFN-γ(-) IL-17(-) IL-22(+) (Th22) cells in peripheral lymphocytes were determined by flow cytometry, and plasma IL-22 autoantibodies were detected by ELISA in 19 new-onset SLE patients and 20 healthy controls. Plasma IL-22 levels in new-onset SLE patients were significantly decreased compared with relapsing SLE patients and healthy controls. After treatment with prednisone and hydroxychloroquine, the levels of plasma IL-22 in new-onset SLE patients were obviously increased but still lower than healthy controls. There was a positive correlation between plasma IL-22 levels and the percentages of Th22 cells, but not Th1 and Th17 cells. Moreover, plasma IL-22 levels as well as peripheral Th17 and Th22 cells correlated with SLE disease activity index (SLEDAI) scores and erythrocyte sedimentation rate (ESR). High frequencies of plasma IL-22 autoantibodies were detected in new-onset SLE patients. However, IL-22 levels did not correlate with IL-22 autoantibody. Decreased plasma IL-22 levels and correlation with Th22 cells may be distinct features in new-onset SLE. Moreover, IL-22 and Th22 cell correlated with SLE disease activity.

Peripheral CD24hiCD27+CD19+B cells subset as a potential biomarker in naïve systemic lupus erythematosus

B cells are likely to play critical roles in the pathogenesis of systemic lupus erythematosus (SLE). Our aim was to investigate the role of peripheral CD24(hi) CD27(+) CD19(+) B cells in Chinese patients with new-onset SLE. Peripheral CD24(hi) CD27(+) CD19(+) B cells were analyzed in 55 new-onset lupus and 36 healthy controls by flow cytometry. All SLE cases were treated with prednisolone and hydroxychloroquine during a 1-year follow-up. Thirteen cases were added with cyclophosphamide or mycophenolate mofetil. The CD24(hi) CD27(+) CD19(+) B cells were analyzed at days 0, 7, 14 and months 1, 3, 6, 9 and 12. Interleukin-10 (IL-10)-producing B cell was detected in eight naïve lupus and 10 healthy controls. Compared to healthy controls, the frequency and number of primary circulating CD24(hi) CD27(+) CD19(+) B cells was significantly reduced in SLE cases (8.22 ± 3.48% vs. 31.67 ± 5.53%, P < 0.0001; 4.04 ± 2.85 vs. 38.66 ± 10.22 10(3) cells/mL, P = 0.0001) before treatment; IL-10(+) CD19(+) B cells and IL-10(+) CD24(hi) CD27(+) CD19(+) B cells also decreased in SLE. Interestingly, primary CD24(hi) CD27(+) CD19(+) B cells inversely correlated with SLE disease activity index (SLEDAI) score. Patients with arthritis and hematologic disorders had a lower primary CD24(hi) CD27(+) CD19(+) B cells. In 48 SLE cases who finished the 1-year follow-up, the frequency and number of CD24(hi) CD27(+) CD19(+) B cells increased from 8.26 ± 3.61% to 25.51 ± 4.56%; 3.99 ± 2.86 to 28.64 ± 11.81 10(3) cells/mm(3) (P < 0.0001), accompanied by a significantly decreased SLEDAI score. Of note, CD24(hi) CD27(+) CD19(+) B cells decreased in some flare cases with an elevated SLEDAI score. These results demonstrate that a lower primary CD24(hi) CD27(+) CD19(+) B cells may be an immunologic aspect of new-onset SLE. CD24(hi) CD27(+) CD19(+) B cells may be a useful tool to evaluate lupus activity and monitor the response to therapy.