scholarly journals Multiple Autoantibodies Display Association with Lymphopenia, Proteinuria, and Cellular Casts in a Large, Ethnically Diverse SLE Patient Cohort

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Rufei Lu ◽  
Julie M. Robertson ◽  
Benjamin F. Bruner ◽  
Joel M. Guthridge ◽  
Barbara R. Neas ◽  
...  
Keyword(s):  
High Throughput ◽  
Lupus Erythematosus ◽  
Conditional Logistic Regression ◽  
Clinical Manifestations ◽  
Study Participant ◽  
Ethnically Diverse ◽  
Racial Groups ◽  
Serum Samples ◽  
Autoantibody Detection ◽  
Ribosomal P

Purpose. This study evaluates high-throughput autoantibody screening and determines associated systemic lupus erythematosus (SLE) clinical features in a large lupus cohort.Methods. Clinical and demographic information, along with serum samples, were obtained from each SLE study participant after appropriate informed consent. Serum samples were screened for 10 distinct SLE autoantibody specificities and examined for association with SLE ACR criteria and subcriteria using conditional logistic regression analysis.Results. In European-American SLE patients, autoantibodies against 52 kD Ro and RNP 68 are independently enriched in patients with lymphopenia, anti-La, and anti-ribosomal P are increased in patients with malar rash, and anti-dsDNA and anti-Sm are enriched in patients with proteinuria. In African-American SLE patients, cellular casts associate with autoantibodies against dsDNA, Sm, and Sm/nRNP.Conclusion. Using a high-throughput, bead-based method of autoantibody detection, anti-dsDNA is significantly enriched in patienets with SLE ACR renal criteria as has been previously described. However, lymphopenia is associated with several distinct autoantibody specificities. These findings offer meaningful information to allow clinicians and clinical investigators to understand which autoantibodies correlate with select SLE clinical manifestations across common racial groups using this novel methodology which is expanding in clinical use.

scholarly journals Metabolomic profiling reveals serum L-pyroglutamic acid as a potential diagnostic biomarker for systemic lupus erythematosus

Rheumatology ◽  
2020 ◽  
Author(s):  
Qiong Zhang ◽  
Xin Li ◽  
Xiaofeng Yin ◽  
Haifang Wang ◽  
Chen Fu ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Metabolic Profiling ◽  
Characteristic Curve ◽  
Clinical Manifestations ◽  
Independent Set ◽  
Pyroglutamic Acid ◽  
Serum Samples ◽  
Medical Progress ◽  
Diagnostic Potential ◽  
Potential Biomarker

Abstract Objective The spectrum of clinical manifestations and serological phenomena of SLE is heterogeneous among patients and even changes over time unpredictably in individual patients. For this reason, clinical diagnosis especially in complicated or atypical cases is often difficult or delayed leading to poor prognosis. Despite the medical progress nowadays in the understanding of SLE pathogenesis, disease-specific biomarkers for SLE remain an outstanding challenge. Therefore, we undertook this study to investigate potential biomarkers for SLE diagnosis. Methods Serum samples from 32 patients with SLE and 25 gender-matched healthy controls (HCs) were analysed by metabolic profiling based on liquid chromatography–tandem mass spectrometry metabolomics platform. The further validation for the potential biomarker was performed in an independent set consisting of 36 SLE patients and 30 HCs. Results The metabolite profiles of serum samples allowed differentiation of SLE patients from HCs. The levels of arachidonic acid, sphingomyelin (SM) 24:1, monoacylglycerol (MG) 17:0, lysophosphatidyl ethanolamine (lysoPE) 18:0, lysoPE 16:0, lysophosphatidyl choline (lysoPC) 20:0, lysoPC 18:0 and adenosine were significantly decreased in SLE patients, and the MG 20:2 and L-pyroglutamic acid were significantly increased in SLE group. In addition, L-pyroglutamic acid achieved an area under the receiver-operating characteristic curve of 0.955 with high sensitivity (97.22%) and specificity (83.33%) at the cut-off of 61.54 μM in the further targeted metabolism, indicating diagnostic potential. Conclusion Serum metabolic profiling is differential between SLE patients and HCs and depicts increased L-pyroglutamic acid as a promising bitformatomarker for SLE.

A unique antiphospholipid assay recognizing phospholipid mixture compared with criteria antiphospholipid immunoassays in lupus patients

Lupus ◽  
2016 ◽  
Vol 26 (6) ◽  
pp. 606-615 ◽  
Author(s):  
Y Zuo ◽  
R Willis ◽  
E Papalardo ◽  
M Petri ◽  
E N Harris ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Case Series ◽  
Likelihood Ratios ◽  
Serum Samples ◽  
Predictive Values ◽  
Pregnancy Morbidity ◽  
Commercial Kits ◽  
Sensitivity Specificity

Background While essential for the classification of antiphospholipid syndrome (APS), anticardiolipin (aCL) assays lack specificity and anti-β2glycoproteinI (anti-β2GPI) assays lack sensitivity in this regard. Our aim was to perform a comparative analysis of the APhL ELISA assay (IgG/IgM) and criteria antiphospholipid (aPL) immunoassays in identifying APS-related clinical manifestations in a large group of patients with systemic lupus erythematosus (SLE). Methods Serum samples from 1178 patients from the Hopkins ( n = 543), LUMINA ( n = 588) and Jamaican SLE cohorts ( n = 47) were examined for IgG/IgM positivity in aCL (in-house), anti-β2GPI (two commercial kits) and APhL (Louisville APL) ELISA assays. Correlation of assay positivity with clinical manifestations and sensitivity, specificity, positive and negative predictive values and likelihood ratios were evaluated. A case series analysis was also performed in patients for whom there was isolated positivity in the specific aPL assays. Results The prevalence of aCL positivity was 34.9%, anti-β2GPI kit A was 22.6%, APhL was 11.5% and anti-β2GPI kit B was 7.6% in the study population. Anti-β2GPI kit B, aCL and APhL assays were correlated with venous thrombosis, while only APhL was significantly correlated with arterial thrombosis and consistently correlated with pregnancy-related morbidity. No significant correlations were noted for anti-β2GPI kit A. Sensitivity was greatest for aCL assays followed by anti-β2GPI kit A, APhL and anti-β2GPI kit B, while specificity was greatest and equal for anti-β2GPI kit B and APhL assays. Conclusions Overall, APhL antibodies, especially IgG, represent a promising biomarker for the classification of APS patients in the context of autoimmunity and in risk assessment with regards to pregnancy morbidity and thrombotic manifestations.

Detection of putative autoantibodies in systemic lupus erythematous using a novel native-conformation protein microarray platform

Lupus ◽  
2020 ◽  
Vol 29 (14) ◽  
pp. 1948-1954
Author(s):  
Anselm Mak ◽  
Nien Yee Kow ◽  
Nur Hafiza Ismail ◽  
Nur Diana Anuar ◽  
Nurul H Rutt ◽  
...  
Keyword(s):  
High Throughput ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Protein Microarray ◽  
Prognostic Significance ◽  
Microarray Platform ◽  
Regulation Of Transcription ◽  
Native Conformation ◽  
Systemic Lupus ◽  
Serum Samples

Objective Conventional immunoassays detect autoantibodies related to systemic lupus erythematosus (SLE) via recognition of epitopes on autoantigens expressed in their denatured rather than native conformational state, casting difficulty in evaluating the genuine pathogenicity of the autoantibodies. We aimed to use a novel high-throughput protein microarray platform to identify autoantibodies against native autoantigens in SLE sera. Methods Sera from SLE patients and those of gender-, age-, and ethnicity-matched healthy controls (HC) were screened against more than 1,600 immune-related antigens of native conformation. The relative fluorescent unit readout from post-assay imaging were subjected to bioinformatics pre-processing and composite normalization. A penetrance fold change (pFC) analysis between SLE and HC samples shortlisted 50 autoantigens that were subjected to an unsupervised cluster analysis. Correlations between the pFC of putative autoantigens and clinical parameters including SLE disease activity index (SLEDAI-2K) and recent SLE flares were explored. Results 381 autoantigens were identified when 15 SLE and 15 HC serum samples were compared. The top 20 autoantigens which elicited autoantibody responses in SLE sera filtered based on the highest pFC were further analyzed. Autoantigens which the putative autoantibodies reacted against are those involved in chromatin organization such as DEK, regulation of transcription activity including REOX4 and ELF4, and negative regulation of NFkB activity such as TRIB3. Additionally, the pFC of these autoantibodies significantly and positively correlated with SLEDAI-2K and recent SLE flares. Conclusion A high-throughput protein microarray platform allows detection and quantification of putative lupus-related autoantibodies which are of potential pathophysiological and prognostic significance in SLE patients.

scholarly journals Serology of Lupus Erythematosus: Correlation between Immunopathological Features and Clinical Aspects

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Emanuele Cozzani ◽  
Massimo Drosera ◽  
Giulia Gasparini ◽  
Aurora Parodi
Keyword(s):  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Clinical Aspects ◽  
Great Effort ◽  
Neuropsychiatric Lupus ◽  
Glomerular Injury ◽  
Drug Induced ◽  
Neonatal Lupus Erythematosus ◽  
Heterogenous Group ◽  
Ribosomal P

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the aberrant production of a broad and heterogenous group of autoantibodies. Even though the presence of autoantibodies in SLE has been known, for more than 60 years, still nowadays a great effort is being made to understand the pathogenetic, diagnostic, and prognostic meaning of such autoantibodies. Antibodies to ds-DNA are useful for the diagnosis of SLE, to monitor the disease activity, and correlate with renal and central nervous involvements. Anti-Sm antibodies are highly specific for SLE. Anti-nucleosome antibodies are an excellent marker for SLE and good predictors of flares in quiescent lupus. Anti-histone antibodies characterize drug-induced lupus, while anti-SSA/Ro and anti-SSB/La antibodies are associated with neonatal lupus erythematosus and photosensitivity. Anti-ribosomal P antibodies play a role in neuropsychiatric lupus, but their association with clinical manifestations is still unclear. Anti-phospholipid antibodies are associated with the anti-phospholipid syndrome, cerebral vascular disease, and neuropsychiatric lupus. Anti-C1q antibodies amplify glomerular injury, and the elevation of their titers may predict renal flares. Anti-RNP antibodies are a marker of Sharp’s syndrome but can be found in SLE as well. Anti-PCNA antibodies are present in 5–10% of SLE patients especially those with arthritis and hypocomplementemia.

scholarly journals POS0755 PREVALENCE AND RELEVANCE OF ANTIBODIES AGAINST CITRULLINATED ALPHA ENOLASE (ANTI-CEP1) IN CONNECTIVE TISSUE DISEASES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 630.1-630
Author(s):  
A. Alunno ◽  
O. Bistoni ◽  
F. Carubbi ◽  
M. Antonucci ◽  
S. Calvacchi ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Lupus Erythematosus ◽  
Bone Erosion ◽  
Disease Onset ◽  
Connective Tissue Diseases ◽  
Clinical Manifestations ◽  
Igg Antibodies ◽  
Serum Samples ◽  
Healthy Donors

Background:Anti-citrullinated alpha enolase antibodies have been investigated in rheumatoid arthritis and associated with bone erosion and interstitial lung disease but little is known about their prevalence and role in connective tissue diseases (CTDs).Objectives:The aim of this study was to investigate the prevalence and relevance of anti-CEP1 antibodies in CTDs.Methods:Serum samples from five independent patient cohorts were assessed: 1) established (est) primary Sjogren’s syndrome (pSS) N=78, 2) est-systemic lupus erythematosus (SLE) N=52, 3) est-systemic sclerosis (SSc) N=71, 4) pSS at disease onset N=30, 5) SLE at disease onset N=46 (cohorts 4 and 5 had at least 3 years of follow-up). Samples from ninety sex and age matched healthy donors (HD) and 200 patients with est-RA (disease controls) were also tested. Anti-CEP1 IgG antibodies were measured with a commercially available ELISA kit (Euroimmun, Luebeck, Germany).Results:Anti-CEP1 titer was significantly higher in est-pSS, est-SLE and est-SSc compared to HD, significantly lower in est-pSS and est-SSc compared to est-RA and comparable in est-SLE versus est-RA. We divided patients in every CTD group based on whether their anti-CEP1 titer was below or above the 25th, 50th and 75th percentile. In est-SLE anti-CEP1 values over the 25th percentile were associated with articular involvement (odds ratio, OR (95% confidence interval, CI)=11.5; 1.9-70.6, p=0.008). In est-pSS, no relationship between anti-CEP1>25th percentile and articular involvement was found but rather an association with rheumatoid factor positivity (OR (95% CI)=4.8, 1.6-14.1, p=0.004) and salivary gland swelling (OR (95% CI)=6.2, 1.3-29.1, p=0.021). In est-SSc no difference could be detected across the 3 groups. Anti-CEP-1 titers in pSS and SLE at onset did not differ from each other, were comparable also to those of HD and significantly lower than those of est-pSS, est-SLE and est-RA patients (all p<0.0001).). Of interest, we could retrieve a serum sample collected at the time of diagnosis for 5 patients from the cohort of established pSS and we observed that anti-CEP1 titers were significantly lower at pSS onset than during follow up (at least 12 months after the diagnosis, p=0.0024). No difference was observed in the clinical presentation at disease onset according to different anti-CEP1 titer and they did not predict the development of new clinical manifestations during follow-up.Conclusion:Anti-CEP-1 antibodies can be detected in CTDs at different title during the disease course and may increase overtime, at least in pSS. Although anti-CEP1 antibodies are associated with specific clinical manifestation in est-CTDs, such as articular involvement in est-SLE, they seem to lack a predictive value for future manifestations when measured at disease onset.References:[1]Alunno A, Bistoni O, Pratesi F et al Rheumatology (Oxford) 2018.[2]Manca ML, Alunno A, D’Amato C et al. Joint Bone Spine 2018.Disclosure of Interests:None declared

scholarly journals Multiplex Autoantibody Detection in Patients with Autoimmune Polyglandular Syndromes

2021 ◽  
Vol 22 (11) ◽  
pp. 5502
Author(s):  
Elena N. Savvateeva ◽  
Marina Yu. Yukina ◽  
Nurana F. Nuralieva ◽  
Marina A. Filippova ◽  
Dmitry A. Gryadunov ◽  
...  
Keyword(s):  
Simultaneous Detection ◽  
Clinical Manifestations ◽  
Multiplex Assay ◽  
Serum Samples ◽  
Endocrine Diseases ◽  
Autoimmune Polyglandular Syndrome ◽  
Healthy Donors ◽  
Organ Specific ◽  
Gad 65 ◽  
Autoantibody Detection

The diagnosis of autoimmune polyglandular syndrome (APS) types 1/2 is difficult due to their rarity and nonspecific clinical manifestations. APS-1 development can be identified with assays for autoantibodies against cytokines, and APS-2 development with organ-specific antibodies. In this study, a microarray-based multiplex assay was proposed for simultaneous detection of both organ-specific (anti-21-OH, anti-GAD-65, anti-IA2, anti-ICA, anti-TG, and anti-TPO) and APS-1-specific (anti-IFN-ω, anti-IFN-α-2a, and anti-IL-22) autoantibodies. Herein, 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies or non-autoimmune endocrine pathologies and from healthy donors were analyzed. The prevalence of autoantibodies differed among the groups of healthy donors and patients with non-, mono- and multi-endocrine diseases. APS-1 patients were characterized by the presence of at least two specific autoantibodies (specificity 99.5%, sensitivity 100%). Furthermore, in 16 of the 18 patients, the APS-1 assay revealed triple positivity for autoantibodies against IFN-ω, IFN-α-2a and IL-22 (specificity 100%, sensitivity 88.9%). No anti-cytokine autoantibodies were found in the group of patients with non-APS-1 polyendocrine autoimmunity. The accuracy of the microarray-based assay compared to ELISA for organ-specific autoantibodies was 88.8–97.6%. This multiplex assay can be part of the strategy for diagnosing and predicting the development of APS.

scholarly journals Immune Response to Enterococcus gallinarum in Lupus Patients Is Associated With a Subset of Lupus-Associated Autoantibodies

2021 ◽  
Vol 12 ◽  
Author(s):  
Harini Bagavant ◽  
Antonina M. Araszkiewicz ◽  
Jessica K. Ingram ◽  
Katarzyna Cizio ◽  
Joan T. Merrill ◽  
...  
Keyword(s):  
Immune Response ◽  
Lupus Erythematosus ◽  
Surrogate Marker ◽  
Healthy Controls ◽  
Igg Antibodies ◽  
Serum Samples ◽  
Specific Subset ◽  
Antibody Titers ◽  
Enterococcus Gallinarum ◽  
Ribosomal P

Interactions between gut microbes and the immune system influence autoimmune disorders like systemic lupus erythematosus (SLE). Recently, Enterococcus gallinarum, a gram-positive commensal gut bacterium, was implicated as a candidate pathobiont in SLE. The present study was undertaken to evaluate the influence of E. gallinarum exposure on clinical parameters of SLE. Since circulating IgG antibodies to whole bacteria have been established as a surrogate marker for bacterial exposure, anti-E. gallinarum IgG antibodies were measured in banked serum samples from SLE patients and healthy controls in the Oklahoma Cohort for Rheumatic Diseases. The associations between anti-E. gallinarum antibody titers and clinical indicators of lupus were studied. Antibodies to human RNA were studied in a subset of patients. Our results show that sera from both patients and healthy controls had IgG and IgA antibodies reactive with E. gallinarum. The antibody titers between the two groups were not different. However, SLE patients with Ribosomal P autoantibodies had higher anti-E. gallinarum IgG titers compared to healthy controls. In addition to anti-Ribosomal P, higher anti-E. gallinarum titers were also significantly associated with the presence of anti-dsDNA and anti-Sm autoantibodies. In the subset of patients with anti-Ribosomal P and anti-dsDNA, the anti-E. gallinarum titers correlated significantly with antibodies to human RNA. Our data show that both healthy individuals and SLE patients were sero-reactive to E. gallinarum. In SLE patients, the immune response to E. gallinarum was associated with antibody response to a specific subset of lupus autoantigens. These findings provide additional evidence that E. gallinarum may be a pathobiont for SLE in susceptible individuals.

scholarly journals Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus

2020 ◽  
Vol 21 (10) ◽  
pp. 3463 ◽  
Author(s):  
Ioannis Parodis ◽  
Emil Åkerström ◽  
Christopher Sjöwall ◽  
Azita Sohrabian ◽  
Andreas Jönsen ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Nuclear Antigen ◽  
Systemic Lupus ◽  
Serum Samples ◽  
Small Nuclear Ribonucleoprotein ◽  
Cytokine Levels ◽  
Nuclear Ribonucleoprotein ◽  
Ribosomal P

We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay. In patients with detectable levels at baseline, interferon (IFN)-α2 levels were lower at month 6 (median; interquartile range (IQR): 8.9; 1.5–54.9 pg/mL) versus baseline (28.4; 20.9–100.3 pg/mL; p = 0.043). Interleukin (IL)-6 (baseline: 7.1; 2.9–16.1 pg/mL) decreased from month 6 (0.5; 0.5–6.3 pg/mL; p = 0.018) and throughout a 24 month follow-up. IL-10 (baseline: 12.6; 2.8–29.7 pg/mL) showed more rapid decreases from month 3 (1.8; 0.6–9.1 pg/mL; p = 0.003). Levels of anti-dsDNA (p < 0.001), anti-Smith antigen (Sm) (p = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) (p < 0.001), anti-Sm-U1RNP complex (p = 0.028), and anti-ribosomal P (p = 0.012) antibodies decreased from month 3 and remained decreased. Anti-Sm positivity at baseline was associated with higher probability and/or shorter time to achieve sustained SLE responder index-4 response (hazard ratio (HR): 2.52; 95% CI: 1.20–5.29; p = 0.015), independently of other factors. Decline of IL-6 levels through month 3 was greater in responders. In summary, belimumab treatment lowered IFN-α2, IL-6, and IL-10 levels, as well as levels of multiple autoantibodies, however after different time spans. Notably, anti-Sm positivity and early decline in IL-6 levels were associated with favorable treatment outcome.

Clinical case of lung lesions in patient with newly diagnosed systemic lupus erythematosus

2019 ◽  
Vol 1 (9) ◽  
pp. 53-57
Author(s):  
T. N. Gavva ◽  
L. V. Kuzmenkova ◽  
Yu. N. Fedulaev ◽  
T. V. Pinchuk ◽  
D. D. Kaminer ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Clinical Case ◽  
Clinical Manifestations ◽  
Lung Damage ◽  
Newly Diagnosed ◽  
Systemic Lupus ◽  
Lung Lesions ◽  
Laboratory Parameters ◽  
Clinical Interest

A case of lung damage in systemic lupus erythematosus (SLE) in a 33-year-old woman is described. This case is of clinical interest due to the complexity of diagnosis due to the fact that SLE is a disease with diverse clinical manifestations involving many organs and systems, which often makes it difficult to timely recognize the onset of the disease. SLE still remains a challenge and requires special attention to the patient s history, clinical and laboratory parameters of the patient, as well as specific immunological examinations.

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