Marker For Systemic Lupus Erythematosus Research Articles

Neutrophils-derived Parameters as Cost-effective Inflammatory, Disease Activity Marker in Systemic Lupus Erythematosus (SLE) and Role in Prediction of Lupus Nephritis

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with various clinical manifestations and approximately 50% of the SLE patients develop lupus nephritis (LN), which increases the risk of renal failure, cardiovascular diseases and overall survival. Objectives: Evaluation of neutrophil-derived parameters (Neut-X, Neut-Y and Neut-Z) as an inflammatory, disease activity marker and as a predictor of nephritis in SLE patients. Material and Methods: In this cross-sectional study, 3 ml K3EDTA blood was taken from 110 SLE patients presented in Department of Clinical Immunology to evaluate neutrophil-derived parameters in Sysmex XT2000i haematology analyser and their correlation with other inflammatory biomarkers like, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as SLE disease activity index-2000 (SLEDAI-2K). 24-hours urine protein levels were also estimated as a marker of renal involvement. Records of renal biopsy were available in 73 SLE patients, who belonged to different morphologic classification of LN. Results: After performing bivariate Spearman correlation analysis (SPSS software, version 26.0), Neut-X (measures cytoplasmic granularity by side scattering) and Neut-Z (vector sum of Neut-X and Neut-Y) showed a significant positive correlation ( r > 0.200, P < .05) with ESR, CRP and SLEDAI-2K while Neut-Y (measures nucleic acid content by sideward fluorescence) showed a significant negative correlation ( r > 0.200, P < .05) with ESR and CRP. Receiver-operating characteristic curve analysis was used to evaluate diagnostic value of 24-hour urine protein and predictive values of neutrophil-derived parameters for renal involvement in SLE patients. Among neutrophil-derived parameters, Neut-X was found to be the best predictor of renal dysfunction with highest AUC of 0.710 (95% CI: 0.604-0.816; cut-off: 1344.50; sensitivity: 84.7%; specificity: 50%) followed by Neut-Z with AUC of 0.707 (95% CI: 0.600-0.813; cut-off: 1403.67; sensitivity: 87.5%; specificity: 50%). Conclusion: Our study shows that neutrophil-derived parameters may be used as novel cost-effective, non-invasive biomarker of disease activity as well as for predicting renal involvement in SLE patients.

Assessment of Arterial Stiffness and Biochemical Markers in Systemic Lupus Erythematosus in the Diagnosis of Subclinical Atherosclerosis.

Patients with systemic lupus erythematosus (SLE) are 2-10 times more likely to develop cardiovascular disease (CVD) than the general population. The assessment of the risk of developing CVD is an important direction for further clinical management. The study was conducted retrospectively and included patients with SLE. The aim of the study was to assess the measurements of pulse wave velocity (PWV), carotid intima-media thickness (CIMT), ankle-brachial index (ABI) and biochemical parameters. Subclinical atherosclerosis was also assessed. The study included 98 patients with SLE with an age- and sex-matched control group of 68 healthy adults. Statistical significance was found in the SLE group and the controls for N-terminal fragment of pro-B-type natriuretic peptide (NT proBNP) (144.87 vs. 36.41 pg/mL, p = 0.0018), high-sensitivity cardiac troponin (hs-cTn) (25.43 vs. 6.38 ng/L, p = 0.0303) and D-Dimer levels (0.73 vs. 0.36 µg/mL, p = 0.0088), left CIMT (1.03 vs. 0.62 mm, p < 0.0001), right CIMT (0.93 vs. 0.63 mm, p < 0.0001) and PWV CF (9.74 vs. 7.98 m/s, p = 0.0294). A positive correlation was found between NT proBNP and PWV CF (r = 0.6880, p = 0.0498) and hs-cTn and PVW carotid-femoral (CF) (r = 0.8862, p = 0.0499) in SLE. A positive correlation was reported between PWV CF and systolic blood pressure (r = 0.5025, p = 0.0487). The measurement of carotid-femoral PWV is a simple, non-invasive, and reproducible method and may independently predict future CVD events and their cause. Further studies are warranted to establish the prognostic value of PWV in patients with SLE, as it may be superior to CIMT measurements in the early stages of vascular disorders.

Platelet-to-lymphocyte ratio: a superior prognostic marker for systemic lupus erythematosus compared to neutrophil-to-lymphocyte ratio and systemic immune-inflammation index

Objective. Novel inflammatory indices are a potential substitute for traditional markers which their correlation and clinical application in different autoimmune diseases are still in question. In this study, we evaluated the association of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) with systemic lupus erythematosus (SLE) activity. Methods. We included 103 SLE patients in our study, compared to a matched pair of 103 healthy individuals. A blood sample was drawn to measure SII, PLR, NLR, C-reactive protein, erythrocyte sedimentation rate, autoantibodies, and complement levels. Independent sample t-test, chi-square, and Mann-Whitney U test were implemented for variables as appropriate. Linear regression was used to evaluate the factors that predict SLE activity. Results. Our study revealed that NLR, PLR, and SII between SLE patients and the control group were significantly different. SII and NLR were correlated with renal manifestations of SLE. PLR was correlated with SLEDAI, and an independent factor of SLE activity after adjusting for multiple factors, but not NLR and SII. Conclusion. We demonstrated that only PLR was an independent predictor of SLE activity. This may suggest that NLR and SII are more nonspecific inflammatory markers, compared to PLR being prognostic of SLE activity.

Comparative analysis of contemporary anti-double stranded DNA antibody assays for systemic lupus erythematosus.

Elevated double-stranded DNA (dsDNA) antibody levels in blood serum are considered a disease-specific marker in systemic lupus erythematosus (SLE), correlate with disease activity and the incidence of lupus nephritis, and can be detected in up to 86% of all SLE cases. Despite the high clinical relevance, the variety of dsDNA antibody testing methods with heterogenous performance in clinical use remains challenging. This study is the first to prospectively investigate the performance of two of today's most commonly applied anti-dsDNA testing methods head-to-head under real-world conditions, as well as their correlation with other clinical and serological disease parameters in SLE patients. In this prospective study, all SLE patients undergoing treatment at the Department of Rheumatology at the University Hospital Bonn within a 13-months period (n=41) and control patients without connective-tissue disease (n=51) were consecutively enrolled and examined. For all study participants' serum samples both anti-dsDNA-NcX enzyme-linked immunoassay testing EUROIMMUN, Luebeck, Germany) and the fluorescence immunoassay ELiA dsDNA (Thermo Fisher Scientific, Waltham, USA) were performed. In addition, demographic data, further laboratory values and disease activity parameters were recorded. Clinical disease activity was assessed by SLEDAI-2K. Both assays showed high specificity (anti-dsDNA-NcX ELISA: 0.9, ELiA dsDNA: 0.959), but there were notable differences in sensitivity (anti-dsDNA-NcX ELISA: 0.51, ELiA dsDNA: 0.38). Pearsons's correlation yielded a positive correlation between anti-dsDNA concentrations and CRP concentrations for the anti-dsDNA-NcX ELISA (R=0.22; p=0.038) and a mild-to-moderate inverse correlation between concentrations of anti-dsDNA and complement C4 for the ELiA dsDNA test (R=-0.22; p=0.045) when SLE and control patients were considered together. Other than, no significant correlation between anti-dsDNA concentrations and clinical or laboratory findings was found for either test procedure. Both anti-dsDNA antibody assays represent reliable examination methods with high specificity for the diagnosis of SLE that fulfill EULAR/ACR requirements. However, the anti-dsDNA-NcX ELISA showed superior sensitivity and significant correlation with disease activity (as measured by CRP concentrations).

PROGNOSTIC VALUE OF DIAGNOSTICLY VALUABLE LABORATORY MARKERS OF SYSTEMIC LUPUS ERYTHEMATOSUS FOR DETERMINING THE PROBABILITY OF COMORBID SYNTROPIC LESIONS OF THE CIRCULATORY SYSTEM ORGANS

&#x0D; &#x0D; Abstract. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects almost all internal organs, among which damage to the organs of the circulatory system (OSC) is not only one of the most common, but also ranks first in the structure of the causes of mortality.&#x0D; The aim of the study. To find out the prognostic value of diagnostically valuable laboratory markers of systemic lupus erythematosus to determine the probability of comorbid syntropic lesions of the circulatory system organs.&#x0D; Materials and methods. The study included 125 patients with SLE with OSC lesions, among whom the vast majority of women (88.00%) were young (average age of patients 42.48 ±1.12 years). Patients were stratified according to the presence of comorbid syntropic lesions of the OSC, i.e. those whose frequency reliably increased with an increase in the degree of activity of SLE – these are retinal angiopathy, capillaritis, Raynaud's syndrome, reticular livedo, atherosclerosis, mitral valve insufficiency, mitral valve sealing, pericardial effusion, pulmonary hypertension, myocarditis, endocarditis, symptomatic arterial hypertension, venous thrombosis. During the study, the prognostic value of diagnostically valuable individual laboratory markers and their constellations was determined. The difference was considered statistically significant if p &lt; 0.050. The relationship was considered confirmed if the association coefficient ≥ 0.50 or the contingency coefficient ≥ 0.30.&#x0D; The results. It was found that for determining the probability of retinal angiopathy in patients with SLE, the constellation with ↑ LDL + ↑ IA + ↑ anti-ds DNA + ↑ ANA has the best prognostic value among diagnostically valuable individual laboratory markers and their constellations; for capillaritis – a separate marker of increased activity of AlT; for Raynaud's syndrome – a separate marker ↓ C3; for reticular livedo – ↑ ESR + ↑ small CIC + ↑ anti-ds DNA + ↑ anti-Sm; for atherosclerosis – ↓ hemoglobin + ↑ LDL + ↑ ANA + ↓ C4; for mitral valve insufficiency – ↑ ESR + ↑ anti-ds DNA + ↑ ANA + ↑ antiphospholipid antibodies Ig M; for mitral valve sealing – ↑ ESR + ↑ LDL + ↑ small CIC + ↑ ANA; for pericardial effusion – erythropenia + ↑ C-RP + ↑ lupus anticoagulant; for pulmonary hypertension – hypercholesterolemia + ↑ LDL + ↑ anti-ds DNA + ↑ ANA; for myocarditis – a separate marker ↓ C4; for endocarditis – not detected; for symptomatic hypertension – ↑ LDL + ↑ anti-ds DNA + ↑ ANA + ↑ anti-SSA (Ro); for venous thrombosis – erythropenia + ↓ hemoglobin + ↑ LDL + ↑ ANA.&#x0D; Conclusions. For each comorbid syntropic lesion of the organs of the circulatory system in patients with systemic lupus erythematosus, a diagnostically valuable separate laboratory marker or their constellation has been determined, which have the best prognostic value for determining the probability of occurrence of these lesions.&#x0D;

Tumour-associated antigens in systemic lupus erythematosus: association with clinical manifestations and serological indicators.

To explore the relationship of tumour-associated antigens (TAAs) with the clinical manifestations and serological markers of SLE. This was a retrospective study. Clinical data of SLE patients were extracted from the electronic medical records, including serum levels of TAAs such as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA125, CA15-3 and cytokeratin 19-fragments (CYFRA21-1). TAA positivity was defined as serum level exceeding the upper limit of the corresponding reference range. A total of 149 SLE patients (SLE group) and 149 age- and sex-matched healthy subjects (control group) were enrolled. Compared with healthy controls, the SLE group had higher positivity rates for CA19-9 and CYFRA21-1, and elevated serum levels of CA125, CA15-3 and CYFRA21-1. SLE patients with TAA positivity were older, had a higher prevalence of serous effusion, pericardial effusion, albuminuria and thrombocytopenia, and lower positivity rate for anti-dsDNA than patients without TAA positivity. The levels of serum creatinine (SCR), blood urea nitrogen, glutamic oxalate transaminase and 24-h urinary protein were also higher in SLE patients with TAA positivity, but platelet count and serum albumin levels were lower. On logistic regression, thrombocytopenia and SCR levels were identified as independent risk factors for TAA positivity. CA125 positivity rate and serum levels of CA125 were associated with SLE disease activity. The positivity rates and serum levels of some TAAs were elevated in SLE, and thrombocytopenia and SCR levels were independent risk factors for TAA positivity.

Comparison of current methods for anti-dsDNA antibody detection and reshaping diagnostic strategies.

Anti-double-stranded DNA antibodies (anti-dsDNA) are considered a specific marker for systemic lupus erythematosus (SLE). Though the Farr technique was once the reference method for their detection, it has been almost entirely replaced by more recently developed assays. However, there is still no solid evidence of the commutability of these methods in terms of diagnostic accuracy and their correlation with the Crithidia luciliae immunofluorescence test (CLIFT). Anti-dsDNA antibody levels were measured in 80 subjects: 24 patients with SLE, 36 disease controls drawn from different autoimmune rheumatic diseases (14 systemic sclerosis, 10 Sjögren's syndrome, nine autoimmune myositis, three mixed connective tissue disease), 10 inflammatory arthritis and 10 apparently healthy blood donors by eight different methods: fluorescence enzyme immunoassay, microdot array, chemiluminescent immunoassay (two assays), multiplex flow immunoassay, particle multi-analyte technology immunoassay and two CLIFT. At the recommended manufacturer cut-off, the sensitivity varied from 67% to 92%, while the specificity ranged from 84% to 98%. Positive agreement among CLIFT and the other assays was higher than negative agreement. Mean agreement among methods assessed by the Cohen's kappa was 0.715, ranging from moderate (0.588) to almost perfect (0.888). Evaluation of the concordance among quantitative values by regression analysis showed a poor correlation index (mean r2, 0.66). The present study shows that current technologies for anti-dsDNA antibody detection are not fully comparable. In particular, their different correlation with CLIFT influences their positioning in the diagnostic algorithm for SLE (either in association or sequentially). Considering the high intermethod variability, harmonization and commutability of anti-dsDNA antibody testing remains an unachieved goal.

Anti-double stranded DNA antibodies: A rational diagnostic approach in limited-resource settings

ContextAnti-double-stranded deoxyribonucleic acid antibodies (dsDNA Abs) are highly specific markers of systemic lupus erythematosus (SLE). Multiple methods are employed for their detection in routine diagnostics. ObjectivesThe aim of this study was to evaluate a diagnostic approach for anti-dsDNA Abs using DNA-ELISA and Crithidia luciliae fluorescence test (CLIFT), in combination with antinuclear antibody (ANA) screening. MethodsWe enrolled 113 patients—53 with SLE, 50 with other systemic autoimmune rheumatic diseases (OSARD), and 10 with non-autoimmune clinical conditions (NAICC).Patients’ samples were tested for anti-dsDNA Abs using an enzyme-linked immunosorbent assay (ELISA) and CLIFT, combined to ANA screening by indirect immunofluorescence assay (ANA-IIFA). ResultsThe mean age of patients was 39.94 ± 15 years (ranges: 11–85 years). Overall, specimens from 77.3%, 11.7%, and 20% of patients with SLE, OSARD and NAICC respectively were ELISA-positive; and those from 54.7% to 4% of patients with SLE and OSARD, respectively, were CLIFT-positive. CLIFT positivity was significantly associated with high ELISA titers (p = 0.002) and homogeneous ANA-IIF pattern (p = 0.0002). ConclusionFor better clinical relevance of anti-dsDNA antibodies, we suggest a combined detection strategy based on ELISA, CLIFT and ANA-IIFA, considering the clinical criteria of SLE.

Integrative Analysis for Elucidating Transcriptomics Landscapes of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease that the immune system attacks healthy cells and tissues. SLE is difficult to get a correct and timely diagnosis, which makes its morbidity and mortality rate very high. The pathogenesis of SLE remains to be elucidated. To clarify the potential pathogenic mechanism of SLE, we performed an integrated analysis of two RNA-seq datasets of SLE. Differential expression analysis revealed that there were 4,713 and 2,473 differentially expressed genes, respectively, most of which were up-regulated. After integrating differentially expressed genes, we identified 790 common differentially expressed genes (DEGs). Gene functional enrichment analysis was performed and found that common differentially expressed genes were significantly enriched in some important immune-related biological processes and pathways. Our analysis provides new insights into a better understanding of the pathogenic mechanisms and potential candidate markers for systemic lupus erythematosus.

Identification of IFI44L as a new candidate molecular marker for systemic lupus erythematosus.

We screened the type I interferon signal pathway factor involved in the pathogenesis of systemic lupus erythematosus (SLE) by whole-genome sequencing in SLE patients and initially analyse their potential functions. Use high-throughput sequencing technology to sequence mRNAs on peripheral blood mononuclear cells from SLE patients and healthy controls,and screen out differentially expressed genes related to the type I interferon (IFN) pathway. Quantitative reverse transcription PCR (RT-qPCR) was utilised to verify the expression of the IFI44L gene in SLE patients and healthy controls, and the correlation between its expression level and clinical test indicators of SLE patients were analysed. The receiver operating characteristic (ROC) analyses were conducted to explore the value of IFI44L for SLE diagnosis. Cell counting kit-8 assay and flow cytometry were used to detect the effects of IFI44L on cell proliferation, apoptosis, and cell cycle. A total of 122 genes were significantly up-regulated and 34 genes were significantly down-regulated in the SLE group compared with the healthy control group in this research. The significantly up-regulated IFI44L in SLE patients was verified by RT-qPCR (p<0.01), furthermore, male SLE patients were significantly higher than that in female SLE patients (p<0.05). Moreover, ROC analyses proved IFI44L may have diagnostic value for SLE. Meanwhile, IFI44L expression level was significantly correlated with platelets, mean platelet volume, red blood cell distribution width to platelet ratio, complement component 3, and C-reactive protein (p<0.05). In addition, under the action of high interferon, IFI44L can resist the proapoptotic effect of IFN-α and improve the proliferation activity of cells. IFI44L may play an important role in SLE pathology through abnormal regulation of the type I interferon signalling pathway.

The diagnostic benefit of antibodies against ribosomal proteins in systemic lupus erythematosus

BackgroundAnti-ribosomal P (anti-Rib-P) antibody is a specific serological marker for systemic lupus erythematosus (SLE) and routinely tested by targeting the common epitope of three ribosomal proteins of P0, P1 and P2. This study aimed to investigate if testing antibodies against individual ribosomal protein, but not the common epitope, is required to achieve the best diagnostic benefit in SLE.MethodsThe study included 82 patients with SLE and 22 healthy donors. Serum antibodies were determined by ELISA and immunoblot.ResultsThe prevalence of each antibody determined by ELISA was 35.4% (anti-Rib-P), 45.1% (anti-Rib-P0), 32.9% (anti-Rib-P1) and 40.2% (anti-Rib-P2) at 99% specificity, respectively. Of 53 patients with negative anti-Rib-P antibody, 21 (39.6%) were positive for anti-Rib-P0, 9 (17.0%) for anti-Rib-P1 and 12 (22.6%) for anti-Rib-P2 antibody. The positive rate of anti-Rib-P antibody detected by ELISA was close to the results by immunoblot (33.4%). Patients with any of these antibodies were featured by higher disease activity and prevalence of skin rashes than those with negative antibodies. Moreover, each antibody was particularly related to some clinical and laboratory disorders. The distribution of subclasses of IgG1–4 was varied with each antibody. Anti-Rib-P0 IgG1 and IgG3 were strongly correlated with disease activity and lower serum complement components 3 and 4.ConclusionsAnti-Rib-P antibody is not adequate to predict the existence of antibodies against ribosomal P0, P1 and P2 protein. The examination of antibodies against each ribosomal protein is required to achieve additional diagnostic benefit and to evaluate the association with clinical and serological disorders as well.

Differential approach to peripheral blood cell ratios in patients with systemic lupus erythematosus and various manifestations

New markers of systemic lupus erythematosus (SLE) activity are under investigation. In recent years, the researchers have been focusing increased attention on the role of haematological indicators in assessing the disease activity. Specifically, neutrophil-, basophil-, eosinophil-, monocyte- and platelet-to-lymphocyte ratios (NLR, BLR, ELR, MLR and PLR) have been considered. The specific objective of this study was to determine the suitability of the haematological markers for the assessment of SLE activity and SLE-related organ damage. This study is a retrospective analysis of 136 patients with SLE (124 women and 12 men) who received chloroquine/hydroxychloroquine (HQ/HCQ) monotherapy or HQ/HCQ therapy combined with low/medium doses of glucocorticoid. All patients were assessed for disease activity using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scale. In addition, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) inflammatory parameters were determined in each patient. NLR, BLR, ELR, MLR and PLR were evaluated and correlated with the SLE activity parameters and inflammatory markers. The mean values of the haematological indicators were compared in particular manifestations of SLE-induced organ damage. For numerical variables, descriptive statistics were calculated: median, standard deviation, minimum and maximum values. The Mann–Whitney U test was used for the comparison of continuous variables in the two groups. The Spearman rank correlation test was used to search for any relationships between variables. A p value < 0.05 was considered to be statistically significant. We have found a positive correlation between ELR, MLR and the SLEDAI scale (r = 0.22 and r = 0.27, respectively). NLR, MLR and PLR ratios were significantly correlated with ESR and CRP. Considerably higher NLR values were found in patients with cutaneous and/or mucosal symptoms and with kidney involvement compared to patients without such involvement (4.26 ± 4.2 vs 3.27 ± 2.7; p = 0.05 and 5.45 ± 5.6 vs 3.05 ± 2.0; p < 0.001 respectively). BLR and MLR were significantly higher in patients manifesting symptoms of vasculitis (0.09 ± 0.1 vs 0.02 ± 0.01; p < 0.001 and 3.1 ± 4.2 vs 0.3 ± 0.1; p < 0.001 respectively), arthritis and/or myositis (0.04 ± 0.09 vs 0.02 ± 0.01; p = 0.01 and 1.02 ± 2.6 vs 0.35 ± 0.4; p = 0.01 respectively), whereas elevated ELR ratios were observed in patients with vasculitis (0.4 ± 0.5 vs 0.08 ± 0.06; p < 0.001) compared to patients without such organ involvement. The PLR marker was substantially higher in patients exhibiting haematological disorders in the course of SLE (276.6 ± 226.4 vs 192.6 ± 133.5; p = 0.01). The results indicate that ELR and MLR are effective markers of SLE activity. The haematological indicators may predict SLE-dependent organ damage, particularly cutaneous, mucosal, arthritic, myositic, haematological and kidney involvement.

Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios in Systemic Lupus Erythematosus: Relation With Disease Activity and Lupus Nephritis

ObjectivesTo investigate the role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as activity markers in systemic lupus erythematosus (SLE) without nephritis and lupus nephritis (LN) patients. Patients and methodsThis study included 60 SLE patients with LN, 60 SLE patients without renal involvement and 30 healthy controls. We analyzed correlations between NLR and PLR and both disease activity and renal affection. ResultsThe NLR of SLE patients was much higher than those of the controls. Both ratios showed significantly increased values in SLE patients with active disease. NLR and PLR were positively correlated with SLEDAI, ESR, and CRP and negatively correlated with C4. SLE patients with LN had higher levels of NLR than those without nephritis. NLR showed positive correlations with BUN, serum urea, serum creatinine and 24h urinary protein. We found NLR to be related to anti-ds-DNA level and renal biopsy classes. While PLR was related only to anti ds-DNA. The best NLR to predict SLE active disease was 2.2 and the best PLR cut-off value was 132.9. ConclusionNLR and PLR are useful inflammatory markers to evaluate disease activity in SLE patients. Also, NLR could reflect renal involvement in SLE patients and is associated with the different classes of its histological staging.

T cell receptor β repertoires as novel diagnostic markers for systemic lupus erythematosus and rheumatoid arthritis

ObjectiveT cell receptor (TCR) diversity determines the autoimmune responses in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is closely associated with autoimmune diseases prognosis and prevention. However, the...

Cell bound complement activation products alone and in combination with low serum complement C3 or C4 have superior diagnostic performance in systemic lupus erythematosus

Abstract BACKGROUND Cell-bound complement activation products (CB-CAPs) are sensitive and specific diagnostic markers of systemic lupus erythematosus (SLE). We compared the performance of CB-CAPs to low serum complement C3 or C4 in distinguishing SLE from other rheumatic diseases and healthy individuals. METHODS Adult subjects (n=1200) were enrolled from multiple academic centers, including SLE (498), healthy individuals (252) and subjects with other rheumatic diseases (450). Erythrocyte bound C4d [EC4d] and B-Lymphocyte bound C4d [BC4d] were quantitated using flow cytometry. Serum C3 and C4 levels were determined using immunoturbidimetry. Measurements included sensitivity, specificity, area under the curve (AUC) of the receiver operating characteristic curve (ROC) and Youden Index, for each marker as well as combinations. RESULTS Abnormal CB-CAPs status yielded 62% sensitivity with 88% specificity in distinguishing SLE from the group with other diseases compared to low C3/C4 status − 38% sensitivity, 93% specificity. Youden index was 0.492±0.03 for CB-CAPs compared to 0.313±0.03 for low C3/C4 (p&amp;lt;0.01). AUC was higher with BC4d (0.72) than with EC4d (0.68; p&amp;lt;0.01), low C3 (0.62; p&amp;lt;0.01), low C4 (0.62; p&amp;lt;0.01) and low C3 and/or C4 levels (0.66; p&amp;lt;0.01). The cumulative complement scoring system yielded higher AUC (0.81). A score with greater than 1 complement abnormality yielded 45% sensitivity and 98% specificity. CONCLUSION Our data suggests that CB-CAPs have greater diagnostic performance than low serum complement C3/C4. The combination of these complement abnormalities in a composite complement score is superior in distinguishing SLE from other rheumatic diseases and healthy individuals.

Thrombocytopenia as a Prognostic Marker for Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis

Systemic lupus erythematosus (SLE) patients often exhibit hematological abnormalities, but the role of thrombocytopenia on the prognosis of SLE shows inconsistent results. The purpose of this meta-analysis was to confirm the impact of thrombocytopenia on mortality and end organ damage in patients with SLE. Three electronic databases, PubMed, Embase and Cochrane library were systematically searched to identify the eligible studies from inception to November 2017 in order to evaluate the impact of thrombocytopenia on the prognosis of patients with SLE. The summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to measure the impact of thrombocytopenia on mortality and end organ damage based on the random-effects model. A total of 8 studies that reported data on 2,158 patients with SLE were included. The summary OR indicated that SLE subjects with thrombocytopenia were significantly associated with an increased risk of mortality (OR: 4.57; 95% CI: 2.28-9.17; P < 0.001) and end-organ damage (OR: 3.31; 95% CI: 1.11-9.86; P = 0.031). Furthermore, the sensitivity analysis indicated stable mortality, while the result for end organ damage was variable. In addition, the patients with thrombocytopenia with disease duration <60 months presented a greater risk for mortality than those with disease duration ≥60.0 months (P = 0.002). Patients with SLE and thrombocytopenia were found to be associated with an increased risk of mortality and end organ damage.

Precipitating anti-dsDNA peptide repertoires in lupus.

Anti-double-stranded (ds)DNA autoantibodies are prototypical serological markers of systemic lupus erythematosus (SLE), but little is known about their immunoglobulin variable (IgV) region composition at the level of the secreted (serum) proteome. Here, we use a novel proteomic workflow based on de novo mass spectrometric sequencing of anti-dsDNA precipitins to analyse IgV subfamily expression and mutational signatures of high-affinity, precipitating anti-dsDNA responses. Serum anti-dsDNA proteomes were oligoclonal with shared (public) expression of immunoglobulin (Ig)G heavy chain variable region (IGHV) and kappa chain variable region (IGKV) subfamilies. IgV peptide maps from eight subjects showed extensive public and random (private) amino acid replacement mutations with prominent arginine substitutions across heavy (H)- and light (L)-chains. Shared sets of L-chain complementarity determining region 3 (CDR3) peptides specified by arginine substitutions were sequenced from the dominantly expressed IGKV3-20 subfamily, with changes in expression levels of a clonal L-chain CDR3 peptide by quantitative multiple reaction monitoring (MRM) paralleling the rise and fall of anti-dsDNA levels by Farr radioimmunoassays (RIA). The heavily mutated IgV peptide signatures of precipitating anti-dsDNA autoantibody proteomes reflect the strong selective forces that shape humoral anti-dsDNA responses in germinal centres. Direct sequencing of agarose gel precipitins using microlitre volumes of stored sera streamlines the antibody sequencing workflow and is generalizable to other precipitating serum antibodies.

Neutrophil to lymphocyte and platelet to lymphocyte ratios in systemic lupus erythematosus: Relation with disease activity and lupus nephritis.

To investigate the role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as activity markers in systemic lupus erythematosus (SLE) without nephritis and lupus nephritis (LN) patients. This study included 60 SLE patients with LN, 60 SLE patients without renal involvement and 30 healthy controls. We analyzed correlations between NLR and PLR and both disease activity and renal affection. The NLR of SLE patients was much higher than those of the controls. Both ratios showed significantly increased values in SLE patients with active disease. NLR and PLR were positively correlated with SLEDAI, ESR, and CRP and negatively correlated with C4. SLE patients with LN had higher levels of NLR than those without nephritis. NLR showed positive correlations with BUN, serum urea, serum creatinine and 24h urinary protein. We found NLR to be related to anti-ds-DNA level and renal biopsy classes. While PLR was related only to anti ds-DNA. The best NLR to predict SLE active disease was 2.2 and the best PLR cut-off value was 132.9. NLR and PLR are useful inflammatory markers to evaluate disease activity in SLE patients. Also, NLR could reflect renal involvement in SLE patients and is associated with the different classes of its histological staging.

Prozone-like phenomenon found in chemiluminescent enzyme immunoassay using magnetic particles for measurement of serum anti-single stranded DNA antibody titers: Definition and management

BackgroundSerum anti-single stranded DNA antibody (anti-ssDNAab) is used as a marker for systemic lupus erythematosus. We found a ‘prozone-like phenomenon,’ which was different from an original prozone phenomenon, in chemiluminescent enzyme immunoassay using magnetic particles for the measurement of serum anti-ssDNAab titers. We investigated mechanisms of the prozone-like phenomenon and countermeasures to prevent it from being overlooked. MethodsThis study examined 679 samples from patients tested for anti-ssDNAab titer at our hospital. In addition, the BF photometry OD value 2 (OD2), an index of optical density, was monitored simultaneously. ResultsThe undiluted samples with a prozone-like phenomenon showed extremely lower OD2. Those samples were able to be distinguished from other samples by setting OD2 criteria based on the 95% prediction interval. Significant differences (p < 0.05) were found in the titer ratios (ten-fold diluted against undiluted) between groups with >1.5 and other groups with <1.5 for the ratios of OD2. ConclusionsWe proposed two valuable methods to find a prozone-like phenomenon: one by setting OD2 criteria based on the 95% prediction interval and the other by analyzing the ratios both in titers and OD2 between undiluted and 10-fold diluted samples.

Neutrophil-Lymphocyte Ratio as a Reliable Predictive Marker in Systemic Lupus Erythematosus

AbstractBackground: SLE is a complex autoimmune disease with heterogenous clinical manifestations and disease course, Nephritis is a major cause of morbidity and mortality in patients with lupus. Many clinical parameters and laboratory markers can be used to evaluate disease activity. NLR is positively associated with inflammatory disorders.Objectives: Is to evaluate the Neutrophil Lymphocytic ratio (NLR) as a reliable predictive and prognostic marker in systemic lupus erythematosus.Methods: The present study was carried out on 60 patients and 20 healthy individuals as controls. Patients were classified into: Group I: 40 SLE patients with active disease, which was sub divided into two subgroups: Group IA included thirty SLE patients with LN and Group IB included ten SLE patients with active disease without nephritis. Group II: 20 SLE patients with inactive disease. Group III: 20 apparently healthy vol-unteers as controls. CBC, serum creatinine, ESR, CRP, ANA, Anti-ds DNA, C3, C4, 24-hour protein in urine and urine analysis were done to all participants.Results: The NLR of SLE patients was significantly higher compared to that of the controls. Furthermore, SLE patients with nephritis had higher NLR levels than those without nephritis.Conclusion: NLR is a useful, simple and bed side inflam-matory marker for assessment of disease activity in patients with SLE. Also, NLR is a promising predictor of lupus ne-phritis.