anti-dsDNA Antibody Levels Research Articles

Autoantibodies from long-lived ‘memory’ plasma cells of NZB/W mice drive immune complex nephritis

ObjectivesWe have previously shown that both short- and long-lived plasma cells (PCs) significantly contribute to autoantibody production in NZB/W mice as a model of lupus nephritis. The aim of this...

Serum Levels of Anti-histone and Anti-double-Strand DNA Antibodies Before and After Laparoscopic Ovarian Drilling in Women with Polycystic Ovarian Syndrome

To determine the serum levels of anti-dsDNA, anti-histone, and anti-nucleosome antibodies after laparoscopic ovarian electrocauterization in patients with polycystic ovarian syndrome (PCOS). Our study was performed on 35 patients with PCOS resistant to medical therapy, 35 patients with unexplained infertility, and 35 healthy fertile individuals. Patients with PCOS underwent laparoscopic electrocauterization while those with unexplained infertility underwent diagnostic laparoscopy. Serum levels of anti-dsDNA, anti-histone, and anti-nucleosome antibodies were measured at baseline and 1month after operation and were compared between groups. Baseline characteristics were similar between groups. Patients with PCOS had significantly higher levels of anti-dsDNA compared to unexplained infertility (p<0.001) and control groups (p=0.001). Anti-histone antibodies were higher in PCOS group compared to control group (p=0.001). In those patients suffering from PCOS, anti-histone antibody increased significantly 1month after ovarian electrocauterization (p=0.017). Similarly, serum levels of anti-nucleosome antibodies increased significantly 1month after operation (p<0.001). Laparoscopic ovarian electrocauterization in patients with PCOS results in increased levels of anti-histone and anti-nucleosome antibodies. Anti-dsDNA, anti-histone, and anti-nucleosome antibodies also increase after diagnostic laparoscopy in those with unexplained infertility. Patients with PCOS have higher levels of anti-dsDNA and anti-histone antibodies compared to those with unexplained infertility and healthy fertile subjects.

Elevated Serum BAFF Levels Are Associated With Rising Anti–Double‐Stranded DNA Antibody Levels and Disease Flare Following B Cell Depletion Therapy in Systemic Lupus Erythematosus

To determine whether serum BAFF levels correlate with relapse or remission in patients with systemic lupus erythematosus (SLE) following B cell depletion therapy (BCDT) and to assess the relationship between serum BAFF levels, B cell numbers, and immunoglobulin and autoantibody levels during active disease, both before and after BCDT. Thirty-five patients with active SLE underwent BCDT with rituximab and were monitored for a minimum of 18 months, using clinical and serologic measures of disease activity. Serum BAFF was measured sequentially by enzyme-linked immunosorbent assay before BCDT and during disease relapse or remission after B cell repopulation. Serum BAFF levels prior to BCDT correlated positively with the numbers of CD19+ B cells and with the levels of IgG and IgA. Following BCDT and subsequent B cell repopulation, BAFF levels were significantly higher during relapse, as compared with disease remission, and were significantly greater than at disease flare prior to BCDT. At the time of relapse after BCDT, serum BAFF levels were inversely correlated with B cell numbers, with flare at lower B cell numbers being associated with the highest BAFF levels. The correlations between serum BAFF levels and levels of IgG and IgA were lost following BCDT, but changes in serum BAFF levels correlated positively with changes in anti-double-stranded DNA (anti-dsDNA) antibody levels during relapse or remission after BCDT. The present findings suggest a significant role of BAFF in driving disease flare after B cell repopulation following BCDT. Sequential BCDT may promote ever-increasing levels of BAFF, accompanied by rising anti-dsDNA antibody levels and disease flare even at low B cell numbers. Therefore, our data justify the judicious use of BAFF blockade in a subgroup of lupus patients after BCDT.

Toll-Like Receptor 2 or Toll-Like Receptor 4 Deficiency Does Not Modify Lupus in MRLlpr Mice

Systemic lupus erythematosus is an autoimmune disease with a high morbidity and nephritis is a common manifestation. Previous studies in murine lupus models have suggest a role for Toll-like receptor 2 and 4. We examined the role of these molecules in MRL lpr mice which is one of the most established and robust murine models. We compared disease parameters in Toll-like receptor 2 or Toll-like receptor 4 deficient mice with their littermate controls. We found no difference in the severity of glomerulonephritis as assessed by histology, serum creatinine and albuminuria when Toll-like receptor 2 or Toll-like receptor 4 deficient MRLlpr mice were compared with Toll-like receptor sufficient controls. We also found similar levels of anti-dsDNA and anti-ssDNA antibodies. These results show that Toll-like receptor 2 and Toll-like receptor 4 do not play a significant role in MRLlpr mice, and therefore they may not be important in human lupus.

Rituximab Therapy in Chinese Patients with Lupus Nephritis

Background: Systemic lupus erythematosus (SLE) is a common autoimmune disease in Chinese, and there is high morbidity and mortality in patients with initial renal involvement or severe nephritis. We investigated the efficacy of B cell depletion therapy with rituximab as treatment of Chinese patients with lupus nephritis (LN).Methods: We enrolled 14 patients with lupus nephritis (LN) from Taipei Veterans General Hospital beginning in 2009. LN was confirmed by clinical and laboratory evaluation. Rituximab was indicated when a patient had proteinuria ( ＞1 g/day urinary protein) that was poorly responsive to treatment with corticosteroids or immunosuppressants. Laboratory examination, including measurements of CBC, creatinine, albumin, C3, C4, anti-dsDNA antibodies, and urinary protein, were performed before rituximab infusion and at 3-month and 6-month follow-ups. Intravenous rituximab was given twice over 2 weeks at a total dosage of 1 or 2 g. The primary endpoint was renal response status at week 24.Results: A total of 14 patients were enrolled from 2009 to 2011. There were 11 females and 3 males and the age range was 18 to 41 years (median: 31 years, IQR 10.5 years). The median urinary protein was 3.38 g/day (IQR: 1.76 to 6.47) before rituximab infusion, and was 1.25 g/day (IQR: 0.49-3.13) at the 6 month follow-up. At week 24, the overall renal response rate (complete + partial response) was 57% (8 of 14 patients). There were improvements in C3 levels (＞20 mg/dL) in 6 patients (43%), improvements in C4 levels (＞10 mg/dL) in 3 patients (21%), and reductions in anti-dsDNA antibody levels (＞50%) in 8 patients (57%).Conclusion: Rituximab appeared to have acceptable efficacy in our group of 14 LN patients. Future controlled studies should examine the long-term safety and efficacy of rituximab and determine the optimal rituximab regimen for Chinese patients with LN.

N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL+/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL+/+ mice were given TCE, NAC or TCE+NAC for 6weeks (TCE, 10mmol/kg, i.p., every 4th day; NAC, 250mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies.

Effect of Xuebijing injection (血必净注射液) on systemic lupus erythematosus in mice

To observe the effects of Xuebijing injection on dendritic cells (DCs) and T lymphocytes, and the potential mechanisms of its therapeutic effect on systemic lupus erythematosus (SLE). A widely used mouse model, SLE-prone BLLF1 mice aged 8-10 weeks, was employed. Mice were randomly divided into 4 groups: a normal group, a model group and two treatment groups treated with Xuebijing Injection with a dose of 6.4 mL/kg via intraperitoneal administration for SLE-prone BLLF1 mice aged 8 weeks (treatment A group) and 10 weeks (treatment B group). Renal tissue sections were stained with Masson's trichrome and periodic acid-silver methenamine. Histopathological changes in the kidney were evaluated by a light microscopy. The capacity of the DCs isolated from the spleen to stimulate the T cell proliferation in response to concanavalin A (Con A) was determined. Compared with the model group, levels of anti-dsDNA antibodies in the two treatment groups decreased remarkablly (P<0.01, P<0.05), and levels of serum creatinine and blood urea nitrogen increased (P<0.01, P<0.05). Pathological changes were found in the kidney in the model group. Histopathological abnormalities were alleviated in the two treatment groups. Treatment with Xuebijing injection also significantly upregulated the expression of CD80, CD86 and major histocompatibility class II by DCs compared with the model group (P<0.05). When splenic T lymphocytes from BLLF1 mice were co-cultured with DCs at ratios of 1:100, 1:150 and 1:200 for 3 and 5 days, the proliferation of T lymphocytes was suppressed compared with the normal group (P<0.05), but this was restored by Xuebijing Injection under the same conditions. In the model group, levels of tumor necrosis factor (TNF)-α in supernatants were significantly elevated compared with the normal group (P<0.01), interleukin-2 levels decreased (P<0.05), while these changes were significantly alleviated in the Xuebijing treatment groups. Xuebijing Injection alleviated renal injury in SLE-prone BLLF-1 mice. The mechanism might be through influencing T cell polarization mediated by DCs, and Xuebijing Injection might be a potential drug that suppresses immune dysfunction in patients with SLE.

Glucocorticoid downregulates expression of IL-12 family cytokines in systemic lupus erythematosus patients

This study aims to investigate expression of interleukin 12 (IL-12) family cytokines IL-12, IL-23, IL-27 and IL-35 in systemic lupus erythematosus (SLE) patients and the effect of glucocorticoid (GC) treatment on their expression. Plasma concentration of IL-12, IL-23, IL-27, IL-35, IL-6 and anti-double-stranded DNA (dsDNA) antibodies in 30 newly diagnosed severe SLE patients and 30 matched healthy subjects was measured by enzyme-linked immunosorbent assay. The correlation between the levels of IL-12 family cytokines and the levels of IL-6 or anti-dsDNA antibodies was analyzed by Spearman rank correlation. Significantly higher levels of plasma IL-12, IL-23, IL-27, IL-35, IL-6 and anti-dsDNA antibodies were observed in SLE patients compared with healthy controls (p < 0.05), and after prednisone treatment, the serum levels of IL-12 family cytokines decreased significantly. Moreover, serum levels of IL-12, IL-23, IL-27 and IL-35 were correlated with serum levels of IL-6 and anti-dsDNA antibodies in pre-treatment as well as post-treatment SLE patients. SLE patients have increased plasma levels of IL-12 family cytokines and GCs can downregulate the expression of them in SLE patients. Therefore, members of the IL-12 family may be involved in the pathophysiological process of SLE.

Overexpression of Epstein–Barr virus-induced gene 3 protein (EBI3) in MRL/lpr mice suppresses their lupus nephritis by activating regulatory T cells

To identify the effect of an imbalance of Th1/Th2 cytokines on the development of autoimmune glomerulonephritis (lupus nephritis), we studied the modification of pathological changes in diffuse proliferative glomerulonephritis (DPGN) and membranous glomerulonephritis (MGN) in MRL/lpr mice, which are animal models of systemic lupus erythematosus (SLE). Transgenic MRL/lpr mice (Tg) that overexpressed Epstein--Barr virus-induced gene 3 (EBI3) showed almost normal renal function, which was demonstrated by healing of glomerulonephritis upon renal histology, as compared to the wild-type MRL/lpr (Wt) mice. The levels of anti-dsDNA antibodies and IgE decreased in the Tg mice compared to Wt mice. Quantitative real-time PCR indicated an increase in the mRNA levels of FoxP3, and a decrease in that of IFNγ in the splenocytes of Tg mice as compared to Wt mice. In addition, flow cytometric analysis showed an increase in CD4+CD25+FoxP3+-T cells in the former, as compared to the latter. Our findings suggest that EBI3-overexpression in MRL/lpr mice induces generation of regulatory T cells, which causes suppression of autoimmune and inflammatory reactions by affecting the Th1/Th2 cytokine balance.

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

Elevated anti-double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993-2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P<0.001), <1 year (82% versus 8%; P<0.001), 1-4 years (53% versus 0%; P<0.001), and >4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE.

The effect of methotrexate on improving serological abnormalities of patients with systemic lupus erythematosus

Objective This was an open-labeled, prospective, control study to determine the efficacy of methotrexate (MTX) for improving serological abnormalities in patients with systemic lupus erythematosus (SLE).Methods Thirty patients with a low serum complement and/or high anti-double-stranded DNA (dsDNA) antibody levels during a prednisolone taper received MTX orally at a dose of 7.5 mg/week over 12–18 months (MTX group). Eighteen SLE patients were selected as controls (control group). At the time of entrance into the study, all patients were receiving < 15 mg/day of prednisolone. The C3, C4, and immunoglobulin (Ig)G, IgA, and IgM levels were measured using a turbidimetric immunoassay. The anti-dsDNA antibody level was measured using the Farr assay.Results Significant increases in C3 and C4 levels and significant decreases in anti-dsDNA antibody, IgG, IgA, and IgM levels from baseline were observed for 3–18 months after the trial in the MTX group but not in the control group. At the end of the study, C3 and/or C4 levels in 96.7 % of the MTX patients and 33.3 % of the control patients were normalized or elevated (p = 0.0001), and anti-dsDNA antibody levels were normalized or lowered in 24 of the 26 MTX patients (92.3 %) and in 50.0 % of the control patients (p = 0.0022). In addition, a significant reduction in SLE Disease Activity Index (SLEDAI) score and a prednisolone-sparing effect were observed for the MTX group but not the control group. A significant increase in mean corpuscular volume of red blood cells, which is indicative of an anti-folic-acid metabolic disorder induced by MTX, was observed only for patients in the MTX group. Five patients (16.7 %) discontinued MTX treatment because of disease flare, and another three (10.0 %) discontinued due to treatment side effects.Conclusion MTX appears to be effective for improving serological abnormalities frequently observed before disease flares in SLE patients on a prednisolone taper.

Diet influences expression of autoimmune-associated genes and disease severity by epigenetic mechanisms in a transgenic mouse model of lupus.

Lupus flares occur when genetically predisposed individuals encounter appropriate environmental agents. Current evidence indicates that the environment contributes by inhibiting T cell DNA methylation, causing overexpression of normally silenced genes. DNA methylation depends on both dietary transmethylation micronutrients and ERK-regulated DNA methyltransferase 1 (DNMT-1) levels. We used transgenic mice to study the effect of interactions between diet, DNMT-1 levels, and genetic predisposition on the development and severity of lupus. A doxycycline-inducible ERK defect was bred into lupus-resistant (C57BL/6) and lupus-susceptible (C57BL/6 × SJL) mouse strains. Doxycycline-treated mice were fed a standard commercial diet for 18 weeks and then switched to a transmethylation micronutrient-supplemented (MS) or -restricted (MR) diet. Disease severity was assessed by examining anti-double-stranded DNA (anti-dsDNA) antibody levels, the presence of proteinuria and hematuria, and by histopathologic analysis of kidney tissues. Pyrosequencing was used to determine micronutrient effects on DNA methylation. Doxycycline induced modest levels of anti-dsDNA antibodies in C57BL/6 mice and higher levels in C57BL/6 × SJL mice. Doxycycline-treated C57BL/6 × SJL mice developed hematuria and glomerulonephritis on the MR and standard diets but not the MS diet. In contrast, C57BL/6 mice developed kidney disease only on the MR diet. Decreasing ERK signaling and methyl donors also caused demethylation and overexpression of the CD40lg gene in female mice, consistent with demethylation of the second X chromosome. Both the dietary methyl donor content and the duration of treatment influenced methylation and expression of the CD40lg gene. Dietary micronutrients that affect DNA methylation can exacerbate or ameliorate disease in this transgenic murine lupus model, and contribute to lupus susceptibility and severity through genetic-epigenetic interactions.

Close Relations between Podocyte Injuries and Membranous Proliferative Glomerulonephritis in Autoimmune Murine Models

Background: Membranous proliferative glomerulonephritis (MPGN) is a major primary cause of chronic kidney disease (CKD). Podocyte injury is crucial in the pathogenesis of glomerular disease with proteinuria, leading to CKD. To assess podocyte injuries in MPGN, the pathological features of spontaneous murine models were analyzed. Methods: The autoimmune-prone mice strains BXSB/MpJ-Yaa and B6.MRL-(D1Mit202-D1Mit403) were used as the MPGN models, and BXSB/MpJ-Yaa⁺ and C57BL/6 were used as the respective controls. In addition to clinical parameters and glomerular histopathology, the protein and mRNA levels of podocyte functional markers were evaluated as indices for podocyte injuries. The relation between MPGN pathology and podocyte injuries was analyzed by statistical correlation. Results: Both models developed MPGN with albuminuria and elevated serum anti-double-strand DNA (dsDNA) antibody levels. BXSB/MpJ-Yaa and B6.MRL showed severe proliferative lesions with T and B cell infiltrations and membranous lesions with T cell infiltrations, respectively. Foot process effacement and microvillus-like structure formation were observed ultrastructurally in the podocytes of both MPGN models. Furthermore, both MPGN models showed a decrease in immune-positive areas of nephrin, podocin and synaptopodin in the glomerulus, and in the mRNA expression of Nphs1, Nphs2, Synpo, Actn4, Cd2ap, and Podxl in the isolated glomerulus. Significant negative correlations were detected between serum anti-dsDNA antibody levels and glomerular Nphs1 expression, and between urinary albumin-to-creatinine ratio and glomerular expression of Nphs1, Synpo, Actn4, Cd2ap, or Podxl.Conclusion: MPGN models clearly developed podocyte injuries characterized by the decreased expression of podocyte functional markers with altered morphology. These data emphasized the importance of regulation of podocyte injuries in MPGN.

AB0407 Combined serum free light chains are associated with active disease in systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is characterised by chronic B cell stimulation and hyperactivity. Due to the complexity and variability observed during the course of SLE, reliable and accurate biomarkers for...

Expression level of the growth factor progranulin is related with development of systemic lupus erythematosus

BackgroundThis study is to investigate the expression of progranulin (PGRN) in systemic lupus erythematosus (SLE) patients and the effect of glucocorticoid (GC) treatment on its expression.MethodsThirty newly diagnosed severe SLE patients and 30 healthy subjects were enrolled in this study. The serum levels of PGRN and the inflammatory factors of SLE were detected by ELISA and the mRNA expression of these proteins were detected by real-time PCR.ResultsThe serum levels of PGRN, IL-6, PR3, TNFR, TNF-α and anti-dsDNA antibody in SLE patients were increased significantly compared with healthy controls (P < 0.05). The relative expression of PGRN mRNA was increased by 4.88-fold in pre-treatment SLE patients compared with controls (P < 0.05). After prednisone treatment, the serum levels of PGRN decreased significantly, and the relative expression of PGRN mRNA was decreased by 1.34-fold compared with the untreated controls (P < 0.01). Moreover, Serum concentration of PGRN was correlated with serum levels of IL-6, TNF-α, TNFR and anti-dsDNA antibody in both pre-treatment and post-treatment SLE patients.ConclusionsPGRN is up-regulated in the SLE patients and is correlated with pro-inflammatory cytokines and anti-dsDNA antibody. Glucocorticoids can down-regulate the expression of PGRN in SLE patients.Virtual slideshttp://www.diagnosticpathology.diagnomx.eu/vs/1562484036905973

Autoantibody induction by DNA-containing immune complexes requires HMGB1 with TLR2/miR-155 pathway (P4040)

Abstract Anti-dsDNA autoantibody has been reported as a central pathogenic factor of SLE. However, the mechanisms of anti-dsDNA antibody production still remain unclear. Recent evidence indicates that circulating DNA-containing immune complexes, one of the hallmarks of SLE, might be involved in the autoantibody production. Here we mainly explored the potential role and underlying mechanisms of DNA-containing immune complexes in the anti-dsDNA antibody production. We found that these immune complexes provoked anti-dsDNA antibody production primarily through their HMGB1 component, whose level was highly and positively correlated with the anti-dsDNA antibody level in SLE patients. Furthermore, the HMGB1-mediated autoantibody production was in a TLR2/MyD88 dependent pattern, and modulated by the miR-155 via targeting Ets-1. Our results firstly reported the crucial role of HMGB1 component of DNA-containing immune complexes in the autoantibody production, which was mediated and regulated by TLR2/MyD88/miR-155/Ets-1 pathways. These findings may provide novel mechanistic insight into the persistent anti-dsDNA antibody production and new clues for the development of therapeutic strategies for SLE.

Autoantibody induction and adipokine levels in patients with psoriasis treated with infliximab

This study was aimed to analyse the prevalence of antinuclear antibodies in patients with psoriasis after treatment with infliximab and correlates the development of antibodies with both response to treatment and adipokines levels. Serum levels of ANA, anti-dsDNA, anti-histone, anti-nucleosome and anti-ENA antibodies at baseline after 2 and 12 months of treatment with infliximab were measured in 27 patients with psoriasis, as well as in 27 matched controls. Serum C-reactive protein (CRP), chemerin, visfatin and resistin were also assessed. The prevalence of ANA increased from 22 to 37% and 63% (p < 0.01) during treatment with infliximab, with a gradual progressive increase both in ANA titre and in percentage of ANA pattern. The prevalence of other antibodies also increased from 7 to 30% and 48% (p < 0.01) for anti-ds-DNA and from 7 to 26% and 37% for anti-nucleosome antibodies (p < 0.05), whereas the prevalence of anti-histone and anti-ENA antibodies was unchanged throughout the study period. Basal chemerin, resistin and CRP levels were higher in patients than in controls, and their levels progressively normalized during treatment (p < 0.01). Conversely, visfatin levels gradually increased (p < 0.01). ANA+ patients tended to show a faster decrease in PASI score, CRP and chemerin levels after 2 months, but the PASI score did not differ between ANA+ and ANA- patients at 12 months. A higher increase of visfatin was also found in ANA+ patients at 2 and 12 months. The antinuclear antibody response induced by infliximab was restricted to ANA, anti-dsDNA and anti-nucleosome antibodies. Patients who developed ANA positivity showed a faster clinical, inflammatory and immunological response to infliximab therapy.

Anti-ribosomal P protein IgG autoantibodies in patients with systemic lupus erythematosus: diagnostic performance and clinical profile

BackgroundThis study was devised to assess the performance of anti-ribosomal P (anti-Rib-P) antibodies in the diagnosis of systemic lupus erythematosus (SLE) and the association of these antibodies with the clinical features of SLE.MethodsWe used a fluorescence enzyme immunoassay to determine anti-Rib-P levels in an SLE group, a rheumatic disease control (RDC) group (rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis), and a healthy control (HC) group. We also determined anti-Smith antigen (anti-Sm) and anti-double-stranded DNA (anti-dsDNA) antibody levels. Receiver operating characteristic (ROC) curves were constructed and the best cut-off points for positivity were determined. Using regression analysis, the relationship between clinical variables and autoantibody levels was analyzed.ResultsIn total, 127 patients with SLE, 256 controls with other rheumatic diseases, and 100 HCs were studied. Anti-Rib-P autoantibodies were positive in 18 (14.2%) of the patients with SLE (mean concentration of 30.6 ± 46.9 U/ml) and in 2 patients with RA (0.8% of the RDC group). In addition, 12 patients with SLE (9.4%) were positive for anti-Sm (31.1 ± 40.8 U/ml) and 63 (49.6%) were positive for anti-dsDNA autoantibodies (88.4 ± 88.5 U/ml). When we assessed the 18 patients with SLE who had tested positive for anti-Rib-P, we found that 4 of these were positive for anti-Rib-P only, whereas 12 were positive for anti-Rib-P plus anti-dsDNA, and 2 were positive for all three antibodies. There were no samples positive for anti-Rib-P plus anti-Sm. The specificity, sensitivity, positive likelihood ratio, and negative likelihood ratio of anti-Rib-P for SLE diagnosis were 99.4%, 14.2%, 23.7%, and 0.86%, respectively.Caucasian ethnicity was associated with lower anti-Rib-P antibody levels. No relation was found between anti-Rib-P levels and neuropsychiatric or other clinical features.ConclusionsAnti-Rib-P autoantibodies have high specificity for SLE, and measurement of these might improve the accuracy of SLE diagnosis. In this study, we found that Caucasian ethnicity was associated with lower anti-Rib-P antibody levels.

Increased CD38 expression in T cells and circulating anti-CD38 IgG autoantibodies differentially correlate with distinct cytokine profiles and disease activity in systemic lupus erythematosus patients

CD38 is a multifunctional protein possessing ADP-ribosyl cyclase activity responsible for both the synthesis and the degradation of several Ca2+-mobilizing second messengers. In mammals, CD38 also functions as a receptor. In this study CD38 expression in CD4+, CD8+, or CD25+ T cells was significantly higher in systemic lupus erythematosus (SLE) patients than in Normal controls. Increased CD38 expression in SLE T cells correlated with plasma levels of Th2 (IL-4, IL-10, IL-13) and Th1 (IL-1β, IL-12, IFN-γ, TNF-α) cytokines, and was more prevalent in clinically active SLE patients than in Normal controls. In contrast, elevated anti-CD38 IgG autoantibodies were more frequent in clinically quiescent SLE patients (SLEDAI=0) than in Normal controls, and correlated with moderate increased plasma levels of IL-10 and IFN-γ. However, clinically active SLE patients were mainly discriminated from quiescent SLE patients by increased levels of IL-10 and anti-dsDNA antibodies, with odds ratios (ORs) of 3.7 and 4.8, respectively. Increased frequency of anti-CD38 autoantibodies showed an inverse relationship with clinical activity (OR=0.43), and in particular with the frequency of anti-dsDNA autoantibodies (OR=0.21). Increased cell death occurred in CD38+ Jurkat T cells treated with anti-CD38+ SLE plasmas, and not in these cells treated with anti-CD38− SLE plasmas, or Normal plasmas. This effect did not occur in CD38-negative Jurkat T cells, suggesting that it could be attributed to anti-CD38 autoantibodies. These results support the hypothesis that anti-CD38 IgG autoantibodies or their associated plasma factors may dampen immune activation by affecting the viability of CD38+ effector T cells and may provide protection from certain clinical SLE features.

A Case of ANA-negative, Anti-dsDNA Negative, and Anti-Ro/SSA Positive Membranous Lupus Nephropathy

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of diverse autoantibodies with various systemic organ involvements. In patients with SLE, autoantibodies, such as antinuclear antibody (ANA) and anti-dsDNA antibody, play an important role not only in diagnosing the disease, but also representing the pathogenesis of the disease. ANA is the main screening tool in diagnosis and serum complement levels and anti-dsDNA antibody level are closely related to the disease activities. Nevertheless, exceptionally, some patients represent with negative ANA and/or anti-dsDNA antibody leading to difficulties in diagnosing the disease. Here, we report a case of 37-year old female SLE patient with negative ANA, negative anti-dsDNA antibody, and positive anti-Ro/SSA antibody, which manifested with nephrotic syndrome.