The additional role of anti-nucleosome antibodies in the prediction of renal damage in systemic lupus erythematosus based on CSTAR (XXV).

OBJECTIVES: The predominant determinant of an unfavorable prognosis among Systemic Lupus Erythematosus (SLE) patients resides in the irreversible organ damage. This prospective cohort study aimed to identify the additional value of anti-nucleosome antibodies on organ damage accumulation in SLE patients. METHODS: Based on the Chinese SLE Treatment and Research group (CSTAR) registry, demographic characteristics, autoantibodies profiles, and clinical manifestations were collected at baseline. Follow-up data were collected by reviewing clinical records. RESULTS: Of 2481 SLE patients with full follow-up data, 663 (26.7%) were anti-nucleosome antibodies positive and 1668 (68.0%) were anti-dsDNA antibodies positive. 764 (30.8%) patients developed new organ damage during a mean follow-up of 4.31 ± 2.60 years. At baseline, patients with positive anti-nucleosome antibodies have a higher rate of lupus nephritis (50.7% vs 36.2%, p < .001). According to the multivariable Cox regression analysis, both anti-nucleosome (HR = 1.30, 95% CI, 1.09-1.54, p < .001) and anti-dsDNA antibodies (HR=1.68, 95% CI, 1.38-2.05, p < .001) were associated with organ damage accumulation. Anti-nucleosome (HR = 2.51, 95% CI, 1.81-3.46, p < .001) and anti-dsDNA antibodies (HR = 1.69, 95% CI, 1.39-2.06, p < .001) were independent predictors for renal damage. Furthermore, the combination of the two antibodies can provide more accurate information about renal damage in overall SLE patients (HR = 3.19, 95% CI, 2.49-4.10, p < .001) and patients with lupus nephritis at baseline (HR = 2.86, 95% CI, 2.29-3.57, p < .001). CONCLUSION: Besides anti-dsDNA antibodies, anti-nucleosome antibodies can also provide information about organ damage accrual during follow-up. The ability of co-positivity of anti-nucleosome and anti-dsDNA antibodies in predicting renal damage may lead to additional benefits in the follow-up of these patients.

Autoantibodies in lupus nephritis useful in distinguishing proliferative nephritis from membranous nephritis.

OBJECTIVES: This study was conducted to determine autoantibodies associated with lupus nephritis (LN), especially those useful in diagnosing proliferative and membranous nephritis. METHODS: A total of 106 patients with LN and 63 patients with systemic lupus erythematosus but no nephritis were enrolled; then, 55 patients were selected from the LN group and were divided into two groups: proliferative nephritis patients (n = 36) and membranous nephritis patients (n = 19). The autoantibody profiles of patients' sera were evaluated using the EUROLINE ANA Profile 3 (IgG) kit. RESULTS: A higher positivity rate of anti-double-stranded DNA antibody and anti-histone antibody was seen in LN patients compared to nonrenal systemic lupus erythematosus patients. In comparing between proliferative and membranous nephritis, the positivity of anti-nucleosome antibody was higher in proliferative nephritis, although it was not statistically significant. However, anti-nucleosome antibody-positive patients with LN had a higher prevalence of haematuria and pyuria, which are strong indications of proliferative nephritis. Also, a significantly higher positivity rate of anti-RNP70 antibody was seen in membranous nephritis compared to proliferative nephritis. CONCLUSIONS: Our results showed that anti-nucleosome and anti-RNP70 antibodies may be predictive nonhistological factors for discriminating between proliferative and membranous LN.

Assessment of anti-nucleosome antibody (ANuA) isotypes for the diagnosis and prediction of systemic lupus erythematosus and lupus nephritis activity.

Our study aims to investigate the serum levels of anti-nucleosome antibody (ANuA) isotypes in patients with systemic lupus erythematosus (SLE) and clarify ANuA isotypes that may diagnose and predict SLE. We detected anti-nucleosome antibodies (ANuA) in the serum from 120 patients with SLE, 99 patients suffering from other autoimmune diseases (OAD), and 50 healthy controls by performing IgG-, IgA-, and IgM-specific ELISAs. The serum levels of total anti-nuclear antibodies (ANA IgG), ANuA IgG subclasses (IgG1, IgG2, IgG3, and IgG4), anti-dsDNA antibodies, and the avidities of ANA IgG were also analysed using ELISAs. The levels of three ANuA isotypes (IgG, IgA, and IgM) were significantly higher in patients with SLE than in patients with OAD and healthy controls (p < 0.05). Moreover, the concentrations of ANuA isotypes increased in the active SLE and lupus nephritis (LN) groups and in patients with SLE presenting high-avidity IgG ANA (p < 0.05). Furthermore, ANuA isotype levels decreased significantly with drug therapy, while anti-dsDNA IgG levels decreased with the same trend. Additionally, ANuA isotypes were positively related to the SLEDAI (SLE Disease Activity Index) score, RAI (relative avidity index) of high-avidity IgG ANAs, and serum anti-dsDNA IgG levels. Last, the sensitivity and specificity values for SLE were 83.33 and 96.67% for ANuA IgG, 85.83 and 93.33% for ANuA IgA, and83.33 and 86.67% for ANuA IgM, respectively. The sensitivity and specificity values for LN were 61.67 and 96.67% for ANuA IgG, 49.17 and 96.67% for ANuA IgA, and 52.50 and 96.67% for ANuA IgM, respectively. In conclusion, we evaluated whether ANuA isotypes represent a diagnostic tool to predict SLE activity and define subsets of patients with LN.

Disease criteria of systemic lupus erythematosus (SLE); the potential role of non-criteria autoantibodies.

Patients with SLE show a broad spectrum of more than 200 autoantibodies. They can be pathogenic, predictive, prognostic or even an epiphenomenon. Here, we discuss different autoantibodies that have not been included in EULAR/ACR 2019 classification criteria. Most of them have been addressed to monitor and detect disease activity and not specifically as classification criteria. Indeed, markers to assess disease activity fluctuate as compared with classification criteria and their validation is different. The development of new methods will probably bring new clinical associations and be evaluated as potential classification criteria.

Utility of anti-C1q and anti-nucleosome antibodies in systemic lupus erythematosus and lupus nephritis in southwestern Colombia / Utilidad de los anticuerpos anti-C1q y anti-nucleosomas en el lupus eritematoso sistémico y la nefritis lúpica en el suroccidente colombiano

ABSTRACT Introduction: Lupus nephritis (LN) is one of the most prevalent and severe complications of systemic lupus erythematosus (SLE), requiring reliable urine and serum biomarkers to evaluate it. Anti-nucleosome and anti-C1q antibodies are associated with LN in several geographic regions. Also, southwest Colombia has a heterogeneous ethnicity, which motivated the evaluation of the frequency and relationship of such markers with LN in this region. Methods: A cross-sectional study was conducted in a health centre in south-west Colombia in 84 patients diagnosed with SLE (57 without LN; 27 with LN) between 2016 and 2018. Demographic and clinical and laboratory features, including anti-dsDNA, complement, and anti-C1q and anti-nucleosome antibodies were compared in these patients. ELISA immunoassays were performed to measure the antibodies of interest in blood samples. Statistical analysis was carried out using STATA14 software (StataCorp, College Station, Texas, USA). Quantitative variables were summarised as means or medians and compared with Mann-Whitney or Two-sample t test. Categorical variables were shown as proportions, and compared with Chi-squared or Fisher's exact test. Correlation analysis between quantitative variables was calculated using Spearman's correlation. Results: Of all 84 patients, 27 patients had LN, of which 16 (59.2%) had a positive test for anti-nucleosome antibodies and 10 (37%) for anti-C1q antibodies. An association was found between anti-C1q and proliferative forms of LN and newly diagnosed LN. A correlation was found between anti-nucleosome and anti-C1q antibodies, and anti-dsDNA and low serum complement concentrations. Conclusion: Although both markers were found in variable percentages in SLE patients and seem not to be specific markers of LN in our population, anti-C1q was associated with proliferative forms of LN and de novo LN.

RESUMEN Introducción: La nefritis lúpica (NL), una de las complicaciones más frecuentes y graves del lupus eritematoso sistémico (LES), requiere biomarcadores confiables de orina y suero para su evaluación. Los anticuerpos anti-nucleosoma y anti-C1q se asocian con la NL en varias regiones geográficas. En el suroccidente colombiano se asienta una etnia heterogénea, lo que motivó la evaluación de la frecuencia y la relación de dichos marcadores con NL en dicha región. Métodos: Realizamos un estudio transversal en un centro de salud en el suroccidente de Colombia, con 84 pacientes diagnosticados con LES (57 sin NL; 27 con NL) entre los anos 2016 y 2018. Se compararon las características demográficas, clínicas y de laboratorio, incluidos los anticuerpos anti-dsDNA, complemento, anti-C1q y anti-nucleosomas entre estos pacientes. Se realizaron inmunoensayos ELISA para medir los anticuerpos de interés en muestras de sangre. El análisis estadístico se llevó a cabo con el software Stata v.14 (Stata-Corp, College Station, Texas, EE. UU.). Las variables cuantitativas se resumieron como medias o medianas y se compararon con la prueba t de Mann-Whitney o Two-sample t test; las variables categóricas se mostraron como proporciones y se compararon con Chi-cuadrado o con la prueba exacta de Fisher. Para el análisis de correlaciones entre variables cuantitativas se calculó el coeficiente de correlación de Spearman. Resultados: Entre los 84 pacientes, 27 presentaban LN, de los cuales 16 (59,2%) tuvieron una prueba positiva para anticuerpos anti-nucleosoma y 10 (37%) para anticuerpos anti-C1q. Se encontró una asociación entre anti-C1q y formas proliferativas de NL, así como formas recientemente diagnosticadas de NL. Hubo una correlación entre los anticuerpos anti-nucleosoma y anti-C1q y el anti-dsDNA y las bajas concentraciones de complemento sérico. Conclusión: Aunque los 2 marcadores se encontraron en porcentajes variables de pacientes con LES y no parecen ser marcadores específicos de NL en nuestra población, la presencia de anti-C1q se asoció con formas proliferativas de NL y NL de novo.

Association of anti-nuclesome and anti C1q antibodies with lupus nephritis in an Egyptian cohort of patients with systemic lupus erythematosus.

INTRODUCTION: Anti-nucleosome and anti-C1q antibodies demonstrated an association with the development of glomerulonephritis in systemic lupus erythematosus (SLE). Some investigators have proposed that monitoring anti-C1q and anti-nucleosome antibodies might be valuable for making predictions about lupus nephritis (LN) and assessment of disease activity as a non-invasive biological marker of renal disease. OBJECTIVES: The current study was proposed to investigate the presence of anti-C1q and anti-nucleosome antibodies in the sera of Egyptian patients with SLE and their association with LN. METHODS: Eighty patients with SLE were included. Patients were classified into, a LN group including 40 cases with active LN (based on the results of renal biopsy and renal SLEDAI≥4) and a non renal SLE group including 40 patients (with no clinical or laboratory evidence of renal involvement that were attributed in the past or present to SLE). They were subjected to full medical history taking, clinical examination, routine laboratory investigations, measurement of antinuclear antibody (ANA), anti-ds DNA, anti-C1q & anti-nucleosome antibodies. RESULTS: Anti-C1q antibody showed a statistically significant association with the presence of vasculitis and nephritis while anti-nucleosome antibody didn't show a significant association with the presence of any clinical features. Double positivity of anti-nucleosome and anti-C1q antibodies showed a statistically significant association with the presence of vasculitis and photosensitivity, high ECLAM score, elevated ESR, low serum albumin and low C3 levels. CONCLUSION: Serum anti-C1q antibody has a significant association with LN while double positive antibodies have a significant association with vasculitis and low C3 levels in Egyptian patients with SLE.

Association of anti-nuclesome and anti C1q antibodies with lupus nephritis in an Egyptian cohort of patients with systemic lupus erythematosus

Abstract Introduction: Anti-nucleosome and anti-C1q antibodies demonstrated an association with the development of glomerulonephritis in systemic lupus erythematosus (SLE). Some investigators have proposed that monitoring anti- C1q and anti-nucleosome antibodies might be valuable for making predictions about lupus nephritis (LN) and assessment of disease activity as a non-invasive biological marker of renal disease. Objectives: The current study was proposed to investigate the presence of anti-C1q and anti-nucleosome antibodies in the sera of Egyptian patients with SLE and their association with LN. Methods: Eighty patients with SLE were included. Patients were classified into, a LN group including 40 cases with active LN (based on the results of renal biopsy and renal SLEDAI≥4) and a non renal SLE group including 40 patients (with no clinical or laboratory evidence of renal involvement that were attributed in the past or present to SLE). They were subjected to full medical history taking, clinical examination, routine laboratory investigations, measurement of antinuclear antibody (ANA), anti-ds DNA, anti-C1q & anti-nucleosome antibodies. Results: Anti-C1q antibody showed a statistically significant association with the presence of vasculitis and nephritis while anti-nucleosome antibody didn't show a significant association with the presence of any clinical features. Double positivity of anti-nucleosome and anti-C1q antibodies showed a statistically significant association with the presence of vasculitis and photosensitivity, high ECLAM score, elevated ESR, low serum albumin and low C3 levels. Conclusion: Serum anti-C1q antibody has a significant association with LN while double positive antibodies have a significant association with vasculitis and low C3 levels in Egyptian patients with SLE.

Optimización del algoritmo diagnóstico de anticuerpos antinucleares / Optimization of the diagnostic algorithm of antinuclear antibodies

Introducción: La prueba de anticuerpos antinucleares es una poderosa herramienta en el diagnóstico de las enfermedades reumáticas. Los anticuerpos antinucleares se determinan en el laboratorio por un algoritmo o secuencia que se inicia con prueba de cribado y sigue con la identificación de las especificidades antinucleares más comunes. Pero, ¿cómo interpretar los resultados discordantes entre los dos niveles de estudio de anticuerpos antinucleares? Objetivo: Determinar las especificidades antinucleares menos frecuentes en pacientes positivos de cribado de ANA y negativos de las especificidades más comunes. Métodos: Estudio prospectivo de 88 pacientes consecutivos remitidos para la detección rutinaria de ANA con resultado positivo de cribado por ensayo inmuno-adsorbente ligado a enzima (ELISA) pero negativo de anticuerpos anti-ADN de doble cadena (dc, IgG) y anti-antígenos nucleares extraíbles comunes (ENAc). Las muestras séricas correspondientes fueron evaluadas por inmunofluorescencia indirecta sobre células de carcinoma epidermoide laríngeo humano (IFI-HEp-2) y por ELISA para la detección individual de ANA específicos. Resultados: La prueba de ANA por IFI/HEp-2 resultó positiva en 56/88 (63,6 por ciento) y las especificidades antinucleares se detectaron en 57/88 (64,8 por ciento) muestras, en el orden decreciente de Anti-Nucs: 16/88 (18,2 por ciento); anti-centrómero (CENP-B): 15/88 (17,0 por ciento); -histona: 15/88 (17 por ciento); -PM/Scl: 13/88 (14,8 por ciento); -ADNsc: 11/88 (12,5 por ciento) y -ENAc individuales: 8/88 (9,1 por ciento). La sensibilidad de la IFI-HEp-2 para las especificidades antinucleares fue de 0,83 (IC95 por ciento: 0,72-0,93). De los pacientes negativos de subserología (26/31), 83,9 por ciento no tenían antecedentes de enfermedad reumática asociada a ANA. Conclusiones: La mayoría de los pacientes con resultados discordantes entre el primer y segundo nivel de ANA fueron positivos de especificidades antinucleares menos comunes, pero de reconocido valor diagnóstico(AU)

Introduction: The antinuclear antibody test is a powerful tool for diagnosing rheumatic diseases. Antinuclear antibodies are determined in the laboratory by an algorithm or sequence that starts with a screening test and continues with the identification of the most common antinuclear specificities. But how to interpret the discordant results between the two levels of study of antinuclear antibodies? Objective: To determine the less frequent antinuclear specificities in positive patients of ANA screening and negative of the most common specificities. Methods: A prospective study was done on 88 consecutive patients referred for the routine ANA screening with a positive result of screening by enzyme-linked immunosorbent assay (ELISA) but negative for anti-double-stranded DNA (dc, IgG) and common extractable anti-nuclear antigens (ENAc). The corresponding serum samples were evaluated by indirect immunofluorescence on human laryngeal epidermoid carcinoma cells (IFI-HEp-2) and by ELISA for the individual detection of specific ANA. Results: The ANA test by IFI / HEp-2 was positive in 56/88 (63.6 percent) and the antinuclear specificities were detected in 57/88 (64.8 percent) samples, in decreasing Anti-Nucs order: 16/88 (18.2 percent); anti-centromere (CENP-B): 15/88 (17.0 percent); -histona: 15/88 (17 percent); -PM / Scl: 13/88 (14.8 percent); -ADNsc: 11/88 (12.5 percent) and -ENAc individual: 8/88 (9.1 percent). The sensitivity of IFI-HEp-2 for antinuclear specificities was 0.83 (95 percent CI: 0.72-0.93). No history of rheumatic disease associated with ANA was read in (26/31) 83.9 percent patients with negative subserology. Conclusions: The majority of patients with discordant results between the first and second level of ANA were positive of less common antinuclear specificities, but of recognized diagnostic value(AU)

The impact of biological treatments on the anti-dsDNA and anti-nucleosome tests.

Background Anti-double stranded DNA antibodies are a very heterogeneous group of antibodies, quite specific for systemic lupus erythematosus. Newer technologies, such as addressable laser bead immunoassays (ALBIA), show great potential as a diagnostic application. The production of anti-double stranded DNA antibodies is often encountered in inflammatory arthritis; however, literature reports that the actual onset of drug induced lupus in patients treated with biological drugs is a rare event. False positive results for anti-double stranded DNA and anti-nucleosome antibodies detected in patients with inflammatory arthritis treated with different biologics prompted the investigation of full autoantibody profiles to evaluate each biomarker's diagnostic performance in systemic lupus erythematosus. The aim of the study was to compare the diagnostic performance of anti-double stranded DNA antibody and anti-nucleosome antibody methods and to evaluate the value of simultaneously measuring anti-double stranded DNA and anti-nucleosome antibodies, along with other anti-nuclear antibody analytes, as biomarkers for systemic lupus erythematosus, using a more appropriate control cohort including inflammatory arthritis patients with a non-clinical drug induced lupus. Methods Anti-double stranded DNA and anti-nucleosome antibody levels were evaluated in 247 patient samples: 70 systemic lupus erythematosus, 177 disease controls (including 97 inflammatory arthritis during treatment with different biologics) using the Bio-Rad BioPlex® 2200. Results Anti-nucleosome antibodies demonstrated greater clinical sensitivity and specificity than anti-double stranded DNA antibodies. At the manufacturers' cut-off range, considering the two markers as a single or combined test, the "anti-double stranded DNA test or anti-nucleosome antibodies" was the most sensitive combination (0.400) with the best negative likelihood ratio (0.62) and negative predictive value (0.803). Conclusion Anti-nucleosome antibodies are a more sensitive and specific biomarker of systemic lupus erythematosus than anti-double stranded DNA antibodies. Anti-nucleosome antibodies and anti-double stranded DNA antibodies are independent and complementary markers of systemic lupus erythematosus diagnosis and, therefore, are strongly suggested as combined tests (positive predictive value = 0.938). Moreover, the combined use of the two tests may help to overcome the decreased specificity percentage of the anti-double stranded DNA test, when considering an inflammatory arthritis cohort under biological therapies. The ALBIA method for anti-nuclear specificity detection allows a full autoantibody assessment, resulting in a much higher clinical specificity for systemic lupus erythematosus in the presence of ≥3 positive markers and significantly more positive likelihood ratio when ≥2 positive markers are present.

Anti-C1q Antibody is Associated with Renal and Cutaneous Manifestations in Asian Indian Patients with Systemic Lupus Erythematosus.

INTRODUCTION: C1q play an important role in clearance of immune complexes and apoptotic cell debris. Impaired clearance leads to exposure of C1 native antigen and development of anti-C1q antibody formation. Anti-C1q antibody is well studied in Systemic Lupus Erythematosus (SLE). Significance of anti-C1q Ab in Indian SLE patients and their clinical manifestations is not clear. AIM: The aim of this study was to investigate associations between anti-C1q antibody and clinical as well as serological markers of SLE. MATERIALS AND METHODS: Retrospective study of SLE patients fulfilling either American College of Rheumatology (ACR) 1990 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria were recruited from inpatients and outpatients services of the Clinical immunology and Rheumatology Department, Christian Medical College at Vellore, India between March 2013 and January 2015. Anti-C1q antibody was assayed by ELISA (Demeditec Diagnostics GmbH, Germany). Logistic regression analysis was performed to find the association of anti-C1q antibodies with serological and clinical parameters in SLE including Lupus Nephritis (LN). RESULTS: Sixty nine patients (54.76%) out of 126 SLE patients had LN. Anti-C1q levels were higher in patients with LN as compared to those without (p<0.05). Anti-C1q antibody was also significantly associated with positive C1q immunofluorescence staining in renal biopsy specimens (p<0.05). Overall, renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) {OR 1.35 (1.08-1.69)}, low C4 {OR 3.11 (1.04-9.26)} and mucocutaneous manifestation {OR 4.72 (1.38-16.05)} were independently associated with anti-C1q levels in serum. CONCLUSION: Renal SLEDAI, low C4 and mucocutaneous manifestations were independently associated with raised anti C1q antibody in SLE patients.

Diagnostic value of anti-nucleosome antibody for juvenile systemic lupus erythematosus / 临床检验杂志

Objective To evaluate the diagnostic value of anti-nucleosome antibody for juvenile systemic lupus erythematosus (JSLE).Methods Fifty-four patients with JSLE,28 patients with non-JSLE and 26 healthy children were chosen in this study.antinuclear antibody(ANA),anti-nucleosome antibody (AnuA),anti-dsDNA antibody,anti-histone antibody (AHA) and anti-Sm antibody were detected by ELISA or western-blot method.The relevant clinical data were collected and analyzed.Results For diagnosis of JSLE,the sensitivity and specificity of AnuA was 77.78％ and 96.30％.The sensitivity of AnuA combined with ANA,anti-dsDNA and antiSm was higher than that of single detection.AnuA usually associated with fever,oral/nasal pharyngeal ulcer,lung damage,lymphocyte absolute value,urine protein and C3 level.Conclusion AnuA can be used as a serum marker for JSLE diagnosis.The detection of AnuA combined with anti-dsDNA and anti-Sm should be more helpful for diagnosis of JSLE.

Significance of anti-nucleosome antibody, anti-C1q antibody and anti-double stranded DNA antibody in diagnosis of lupus nephritis / 吉林大学学报(医学版)

Objective:To investigate the clinical and laboratory characteristics of lupus nephritis(LN) patients by detecting the anti-nucleosome antibodies, anti-C1q antibodies and anti-double stranded antibodies(anti-ds DNA), and to clarify the risk factors of LN in the patients with systemic lupus erythematosus(SLE),and the significance of three kinds of antibodies in diagnosis of LN.Methods:A total of 120 SLE patients were selected and divided into LN group(n=60) and non-LN group(n=60).The ANAS data of 120 patients were retrospectively analyzed,the levels of anti-C1q antibodies were measured.The clinical symptoms and laboratory data of the patients with positive anti-dsDNA,-nucleosome and-C1q antibodies (3-pos group)and negative three kinds of antibodies(non 3-pos group) were analyzed in LN group.Results:The positive rate of anti-C1q antibody of the patients in LN group (40.00%) was higher than that in non-LN group (21.67%) (χ2=4.728, P=0.03).The positive rate of anti-dsDNA antibody in LN group was 66.67%, and it was 46.67% in non-LN group;the positive rates of the patients had significant difference between two groups (χ2=4.887, P=0.027).The positive rate of anti-nucleosome antibody in LN group was 58.33%, and it was 40.00% in non-LN group;the positive rates of the patients had significant difference between two groups (χ2=4.034, P=0.045).The positive rates of U1-snRNP, SmD1 and other antibodies Jo-1, SSA/Ro60kD, SSA/Ro52kD, SSB, ScL-70, CENP-B,and P0 had no significant differences between two groups(P>0.05).The levels of C3 and C4 and hemoglobinin of the patients in 3-pos group were higher than those innon 3-pos group (P0.05).The clinical symptoms were not statistically significant in 3-pos and non 3-pos groups (P>0.05).Conclusion:The anti-nucleosome, anti-C1q and anti-dsDNA antibodies are the risk factors of SLE complicated with LN;the positive antibodies can improve the diagnostic rate of LN.The 3-pos patients have more severe damage in complements and blood system with higher renal disease activities.

Identificación de predictores serológicos de recaída en pacientes con lupus eritematoso sistémico: estudio prospectivo de 12 meses / Identification of relapse aerological predictors in patients with systemic lupus erythematous: a prospective study of 12 months

Introducción: las investigativos efectuadas no han tenido éxito en la búsqueda de biomarcadores serológicos o clínicos suficientemente confiables para predecir las recaídas en el lupus eritematoso sistémico (LES). Objetivo: definir el valor predictivo de las especificidades de anticuerpos antinucleares para la recaída del LES y de la nefritis lúpica. Métodos: estudio analítico, observacional, longitudinal y prospectivo en 120 pacientes adultos con LES inactivo (SLEDAI-2K ≤ 5 puntos). La presencia basal de siete especificidades antinucleares, C3 y C4 bajos se correlacionaron con la ocurrencia de recaída del LES (incrementos en la puntuación de SLEDAI-2K ≥ 4) y de la nefritis lúpica mediante análisis univariado. Las variables más valiosas fueron evaluadas adicionalmente como predictoras con un modelo de regresión logística multivariada para calcular los odds ratio (OR). Resultados: las recaídas del LES y de la nefritis lúpica se observaron en 51 (42,5 por ciento) y 29 (24,2 por ciento) de los pacientes, respectivamente. En el análisis multivariado emergieron como factores de riesgo para la recaída del LES la presencia de los anticuerpos anti-Nu (OR= 1523,0; p < 0,001) y los anti-DNAdc (OR= 12,1; p= 0,044) y de la nefritis lúpica, los anti-Nu (OR= 92,9; p< 0,001) y el C3 bajo (OR= 7,1; p= 0,007), La sub-representación de los anti-RNP resultó un factor de riesgo para la recaída del LES y de la nefritis lúpica (OR= 0,023; p= 0,009 y OR= 0,1; p= 0,025). Conclusiones: los pacientes con LES positivos de anticuerpos anti-Nu, anti-DNAdc o niveles bajos del C3 presentaron un riesgo mayor de recaída del LES y de la nefritis lúpica en los próximos 12 meses, lo que señala la necesidad de estrechar su monitoreo clínico(AU)

Introduction: the research carried out have not been successful in finding serological biomarkers or sufficiently reliable biomarkers for predicting relapse in systemic lupus erythematosus (SLE). Objective: setermine the predictive value of specific antinuclear antibodies for relapse of SLE and lupus nephritis. Methods: an analytical, observational, longitudinal and prospective study was carried out in 120 adult patients with inactive SLE (SLEDAI-2K ≤ 5 points). The baseline presence of seven antinuclear specificities, low C3 and C4 were correlated with the occurrence of SLE relapse (increases in score SLEDAI-2K ≥ 4) and lupus nephritis by univariate analysis. The most valuable variables were further evaluated as predictors a multivariate logistic regression model to calculate the odds ratio (OR). Results: SLE and lupus nephritis relapses were observed in 51 (42.5 percent) and 29 (24.2 percent) patients, respectively. The presence of anti-Nu (OR= 1523.0, P < 0.001) antibodies and anti-dsDNA (OR= 12.1; p = 0.044) and lupus nephritis, anti-Nu (OR= 92.9; p < 0.001) and low C3 (OR= 7.1; p= 0.007) emerged as risk factors for relapse of SLE in multivariate analysis. The underrepresentation of anti-RNP was a risk factor for relapse of SLE and lupus nephritis (OR = 0.023; p= 0.009; OR = 0.1; p= 0.025). Conclusions: SLE patients with positive anti-Nu, anti-dsDNA and low levels of C3 had a higher risk of relapse of SLE and lupus nephritis in the succeeding 12 months, signaling the need for close clinical monitoring(AU)

Identificación de predictores serológicos de recaída en pacientes con lupus eritematoso sistémico: estudio prospectivo de 12 meses / Identification of relapse aerological predictors in patients with systemic lupus erythematous: a prospective study of 12 months

Introducción: las investigativos efectuadas no han tenido éxito en la búsqueda de biomarcadores serológicos o clínicos suficientemente confiables para predecir las recaídas en el lupus eritematoso sistémico (LES).Objetivo: definir el valor predictivo de las especificidades de anticuerpos antinucleares para la recaída del LES y de la nefritis lúpica.Métodos: estudio analítico, observacional, longitudinal y prospectivo en 120 pacientes adultos con LES inactivo (SLEDAI-2K ≤ 5 puntos). La presencia basal de siete especificidades antinucleares, C3 y C4 bajos se correlacionaron con la ocurrencia de recaída del LES (incrementos en la puntuación de SLEDAI-2K ≥ 4) y de la nefritis lúpica mediante análisis univariado. Las variables más valiosas fueron evaluadas adicionalmente como predictoras con un modelo de regresión logística multivariada para calcular los odds ratio (OR).Resultados: las recaídas del LES y de la nefritis lúpica se observaron en 51 (42,5 por ciento) y 29 (24,2 por ciento) de los pacientes, respectivamente. En el análisis multivariado emergieron como factores de riesgo para la recaída del LES la presencia de los anticuerpos anti-Nu (OR= 1523,0; p < 0,001) y los anti-DNAdc (OR= 12,1; p= 0,044) y de la nefritis lúpica, los anti-Nu (OR= 92,9; p< 0,001) y el C3 bajo (OR= 7,1; p= 0,007), La sub-representación de los anti-RNP resultó un factor de riesgo para la recaída del LES y de la nefritis lúpica (OR= 0,023; p= 0,009 y OR= 0,1; p= 0,025).Conclusiones: los pacientes con LES positivos de anticuerpos anti-Nu, anti-DNAdc o niveles bajos del C3 presentaron un riesgo mayor de recaída del LES y de la nefritis lúpica en los próximos 12 meses, lo que señala la necesidad de estrechar su monitoreo clínico(AU)

Introduction: the research carried out have not been successful in finding serological biomarkers or sufficiently reliable biomarkers for predicting relapse in systemic lupus erythematosus (SLE).Objective: setermine the predictive value of specific antinuclear antibodies for relapse of SLE and lupus nephritis.Methods: an analytical, observational, longitudinal and prospective study was carried out in 120 adult patients with inactive SLE (SLEDAI-2K ≤ 5 points). The baseline presence of seven antinuclear specificities, low C3 and C4 were correlated with the occurrence of SLE relapse (increases in score SLEDAI-2K ≥ 4) and lupus nephritis by univariate analysis. The most valuable variables were further evaluated as predictors a multivariate logistic regression model to calculate the odds ratio (OR).Results: SLE and lupus nephritis relapses were observed in 51 (42.5 percent) and 29 (24.2 percent) patients, respectively. The presence of anti-Nu (OR= 1523.0, P < 0.001) antibodies and anti-dsDNA (OR= 12.1; p = 0.044) and lupus nephritis, anti-Nu (OR= 92.9; p < 0.001) and low C3 (OR= 7.1; p= 0.007) emerged as risk factors for relapse of SLE in multivariate analysis. The underrepresentation of anti-RNP was a risk factor for relapse of SLE and lupus nephritis (OR = 0.023; p= 0.009; OR = 0.1; p= 0.025).Conclusions: SLE patients with positive anti-Nu, anti-dsDNA and low levels of C3 had a higher risk of relapse of SLE and lupus nephritis in the succeeding 12 months, signaling the need for close clinical(AU) monitoring(AU)

Reactivity in ELISA with DNA-loaded nucleosomes in patients with proliferative lupus nephritis.

Autoantibodies against nucleosomes are considered a hallmark of systemic lupus erythematosus (SLE). We compared in patients with proliferative lupus nephritis the diagnostic usefulness of a dsDNA-loaded nucleosome ELISA (anti-dsDNA-NcX) with ELISAs in which dsDNA or nucleosomes alone were coated. First, we analysed whether DNA loading on nucleosomes led to masking of epitopes by using defined monoclonal anti-DNA, anti-histone and nucleosome-specific autoantibodies to evaluate the accessibility of nucleosomal epitopes in the anti-dsDNA-NcX ELISA. Second, autoantibody levels were measured in these 3 ELISAs in 100 patients with proliferative lupus nephritis (LN) before immunosuppressive treatment and in 128 non-SLE disease controls. In patients with LN inter-assay comparisons and associations with clinical and serological parameters were analysed. The panel of monoclonal antibodies revealed that all epitopes were equally accessible in the anti-dsDNA-NcX ELISA as in the two other ELISAs. Patients with proliferative lupus nephritis were positive with dsDNA-loaded nucleosomes in 86%, with DNA in 66% and with nucleosomes in 85%. In the non-lupus disease control group these frequencies were 1.6% (2 out of 128) for both the anti-dsDNA-NcX and the anti-dsDNA ELISA and 0% in the anti-nucleosome ELISA. The levels in the anti-dsDNA-NcX ELISA were high in a group of patients with LN that showed absent reactivity in the anti-DNA or low levels in the anti-nucleosome ELISA. Anti-dsDNA-NcX positivity was associated with higher SLEDAI scores within this group. Within nucleosome-based ELISAs, we propose the anti-dsDNA-NcX ELISA as the preferred test system.

Anti-nucleosome antibodies outperform traditional biomarkers as longitudinal indicators of disease activity in systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to determine whether anti-nucleosome antibodies function as activity-specific biomarkers in SLE. METHODS: Fifty-one patients were recruited and followed prospectively with periodic clinical and biochemical assessments over a 14-month period. Disease activity was determined by the SLEDAI-2K. Anti-nucleosome antibody levels were measured by an ELISA and its utility as an activity-specific biomarker as compared with that of anti-dsDNA antibodies and C3 was assessed both at baseline and in longitudinal analysis. RESULTS: Anti-nucleosome antibodies were significantly elevated in SLE patients vs controls and showed a moderate positive correlation with disease activity. The utility of anti-nucleosome antibodies in identifying patients with active disease in a cross-sectional analysis was comparable to that of anti-dsDNA antibodies and C3. Analysis of variance demonstrated that the level of anti-nucleosome antibodies and C3 varied significantly with changes in disease activity over time. Changes in clinical state were not mirrored by changes in anti-dsDNA antibodies. In time-dependent analysis, anti-nucleosome antibodies showed a better fit over time than anti-dsDNA antibodies and C3. In pairwise comparisons, C3 and anti-nucleosome antibodies outperformed other models, including the conventional pairing of C3 and anti-dsDNA antibodies, however, no biomarker alone or as a group accurately predicted impending remissions or exacerbations. CONCLUSION: Anti-nucleosome antibodies demonstrate greater fidelity as a biomarker for changes in SLE disease activity than traditional biomarkers, supporting the routine monitoring of this antibody in clinical practice.

Autoanticuerpos como biomarcadores de actividad de la enfermedad del lupus eritematoso sistémico / Autoantibodies as biomarkers of disease activity in systemic lupus erythematosus

Hay una necesidad urgente de biomarcadores que permitan identificar y predecir las fases de actividad del lupus eritematoso sistémico (LES) para optimizar el manejo clínico de los pacientes. De la centena de autoanticuerpos presentes en los pacientes con LES muy pocos son candidatos para biomarcadores de actividad clínica de la enfermedad y ninguno se ha establecido como criterio independiente para la toma de decisiones clínicas. Identificar las recaídas del LES es más arte que ciencia. Recientemente se ha señalado que la correlación positiva entre los niveles de autoanticuerpos y la actividad del LES puede estar subvertida por la presencia de autoanticuerpos protectores que se oponen al daño hístico que producen los autoanticuerpos patogénicos. Los anticuerpos anti-nucleosoma, anti-DNA de doble cadena y anti-C1q están asociados a la actividad de la enfermedad evaluada por varios sistemas de puntuación internacionales como el SLEDAI, ECLAM y BILAG, mayormente en estudios transversales. Estos biomarcadores resultan prometedores para el seguimiento clínico de pacientes con LES, pero aún necesitan la validación de estudios controlados multicéntricos de gran escala. Se hizo esta revisión para resumir los retos del descubrimiento y validación de los autoanticuerpos biomarcadores de actividad del LES en el marco de la complejidad funcional de los autoanticuerpos...

There is an urgent need for biomarkers to identify and predict activity phases of systemic lupus erythematosus (SLE) to optimize the patients clinical management. Out of hundreds of autoantibodies present in SLE patients, very few are candidates for biomarkers of clinical disease activity and none has been established as an independent criterion for clinical decision making. Identifying relapse of SLE is more art than science. It has recently been suggested that the positive correlation between autoantibody levels and SLE activity may be subverted by the presence of protective autoantibodies opposed to tissue damage produced by pathogenic autoantibodies. The anti-nucleosome, anti-dsDNA and anti-C1q antibodies are associated with disease activity assessed by several international rating systems such as the SLEDAI, BILAG ECLAM and, partly in cross-sectional studies. These biomarkers are promising for clinical monitoring of SLE patients, but they still need the validation of multi-scale controlled studies. This review was to summarize the challenges of discovery and validation of biomarkers of autoantibodies in SLE activity within the functional complexity of the autoantibodies...

Autoanticuerpos como biomarcadores de actividad de la enfermedad del lupus eritematoso sistémico / Autoantibodies as biomarkers of disease activity in systemic lupus erythematosus

Hay una necesidad urgente de biomarcadores que permitan identificar y predecir las fases de actividad del lupus eritematoso sistémico (LES) para optimizar el manejo clínico de los pacientes. De la centena de autoanticuerpos presentes en los pacientes con LES muy pocos son candidatos para biomarcadores de actividad clínica de la enfermedad y ninguno se ha establecido como criterio independiente para la toma de decisiones clínicas. Identificar las recaídas del LES es más arte que ciencia. Recientemente se ha señalado que la correlación positiva entre los niveles de autoanticuerpos y la actividad del LES puede estar subvertida por la presencia de autoanticuerpos protectores que se oponen al daño hístico que producen los autoanticuerpos patogénicos. Los anticuerpos anti-nucleosoma, anti-DNA de doble cadena y anti-C1q están asociados a la actividad de la enfermedad evaluada por varios sistemas de puntuación internacionales como el SLEDAI, ECLAM y BILAG, mayormente en estudios transversales. Estos biomarcadores resultan prometedores para el seguimiento clínico de pacientes con LES, pero aún necesitan la validación de estudios controlados multicéntricos de gran escala. Se hizo esta revisión para resumir los retos del descubrimiento y validación de los autoanticuerpos biomarcadores de actividad del LES en el marco de la complejidad funcional de los autoanticuerpos(AU)

There is an urgent need for biomarkers to identify and predict activity phases of systemic lupus erythematosus (SLE) to optimize the patients clinical management. Out of hundreds of autoantibodies present in SLE patients, very few are candidates for biomarkers of clinical disease activity and none has been established as an independent criterion for clinical decision making. Identifying relapse of SLE is more art than science. It has recently been suggested that the positive correlation between autoantibody levels and SLE activity may be subverted by the presence of protective autoantibodies opposed to tissue damage produced by pathogenic autoantibodies. The anti-nucleosome, anti-dsDNA and anti-C1q antibodies are associated with disease activity assessed by several international rating systems such as the SLEDAI, BILAG ECLAM and, partly in cross-sectional studies. These biomarkers are promising for clinical monitoring of SLE patients, but they still need the validation of multi-scale controlled studies. This review was to summarize the challenges of discovery and validation of biomarkers of autoantibodies in SLE activity within the functional complexity of the autoantibodies(AU)

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

OBJECTIVES: 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). METHODS: 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 1 month after operation and were compared between groups. RESULT: 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 1 month after ovarian electrocauterization (p = 0.017). Similarly, serum levels of anti-nucleosome antibodies increased significantly 1 month after operation (p < 0.001). CONCLUSION: 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.

Diagnostic criteria for systemic lupus erythematosus: a critical review.

Systemic lupus erythematosus is a multi-organ system autoimmune disease with clinical and serological heterogeneity. The formulation of initial criteria for SLE was first proposed by the American College of Rheumatology and appeared in 1971. Although the original purpose of the criteria was to classify the disease, it became widely used as a diagnostic criteria in clinical situations. Since then the ACR criteria have undergone at least two changes (in 1982 and 1997). Clinical manifestations that can differentiate SLE patients from healthy people such as skin lesions, arthritis, renal disorder, neurologic disorder, hematologic changes and others are included in these criteria. Serum anti-nuclear antibody, anti-ds-DNA antibody and anti-Sm antibody are important biomarkers of SLE patients. In 2012, the Systemic Lupus Collaborating Clinics proposed the SLICC criteria for SLE in view of new knowledge of autoantibodies and the importance of low complement. Future biomarkers may be useful in distinguishing SLE from other diseases and in monitoring of disease activity.