Clinical implications of discordance between anti-dsDNA antibodies by multiplex flow immunoassay and Crithidia luciliae assay in a multiethnic racial cohort of patients with SLE

Objective Anti-dsDNA antibodies (anti-dsDNA) are a component of all classification schemes in SLE and comprise one of the domains in validated activity indices. Anti-dsDNA is frequently measured commercially by an enzyme immunoassay (EIA) or Crithidia luciliae immunofluorescence test (CLIFT). To address the clinical impact of measuring these antibodies by two different assays, this study leveraged a well-phenotyped multiethnic/racial cohort.Methods All patients fulfilled the classification criteria for SLE by at least one of the validated schemes: American College of Rheumatology, Systemic Lupus Erythematosus International Collaborating Clinics and/or American College of Rheumatology/European League Against Rheumatism classification criteria. Patients with one or more simultaneously paired anti-dsDNA by multiplex EIA and CLIFT were identified. Analysis of concordance or discordance, titre comparability of assays and association with hybrid SLE Disease Activity Index score, prevalence of lupus nephritis (LN), ability to predict a flare and classification criteria was performed.Results 207 patients were simultaneously tested by EIA and CLIFT at least once for anti-dsDNA, generating 586 paired results. 377 pairs were concordant and 209 were discordant. 41 of 207 patients always had discordant paired results and 39 patients always had results with titre discordance. In 100 patients with LN, 60 were positive by EIA and 72 by CLIFT. Sensitivities and specificities for patients with LN versus patients without LN were EIA 60% and 47%, and CLIFT 72% and 37%, respectively. 42 patients had flare assessment within 90 days of their paired result. Six of seven patients with mild flares and all four patients with severe flares had concordant positive results.Conclusion Our data demonstrate that discordance of positivity between both assays for anti-dsDNA is relatively common, occurring in a fifth of patients overall and a third of visits. EIA positivity is associated with LN less often than CLIFT positivity. With the significant discordance of results between anti-dsDNA assays, obtaining both CLIFT and EIA assays may be beneficial for classification and routine monitoring of SLE

Proteomic Architecture of Valvular Extracellular Matrix: FNDC1 and MXRA5 Are New Biomarkers of Aortic Stenosis

Este estudio analizó la expresión de las proteínas de la matriz extracelular (ECM) durante la calcificación de la válvula aórtica con espectrometría de masas y luego se validó en una cohorte humana independiente utilizando datos de RNAseq. El estudio revela que la calcificación de la válvula está asociada con una interrupción significativa en la ECM y las vías metabólicas, y destaca una fuerte conexión entre los marcadores metabólicos y la remodelación de la ECM. También identifica FNDC1 y MXRA5 como nuevos biomarcadores de ECM en válvulas calcificadas, eligiéndolos como objetivos potenciales en el desarrollo y la progresión de la estenosis aórtica.https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=00005140120000-0003-0336-9682https://scienti.minciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000002911sandra.guauque@campusucc.edu.cohttps://scholar.google.ca/citations?user=9uoINksAAAAJ&hl=e

Additional file 1 of Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network

Additional file 1: Supplemental Table 1. Agreement in response status (complete or partial) across visits using non-responder imputation for missing data. Supplemental Table 2. Predictors of response (complete or partial) at both weeks 26 and 52 versus no response at all visits from logistic regression using non-responder imputation for missing response data and multiple imputation for missing covariate data. Supplemental Table 3. Predictors of response (complete or partial) at week 52 versus no response from logistic regression analysis using non-responder imputation for missing response data and multiple imputation for missing covariate data. Supplemental Table 4. Predictors of response (complete or partial) at week 52 versus no response from logistic regression analysis for Class V cases only. Supplemental Table 5. Predictors of week 52 response using multinomial regression with available data. Supplemental Figure 1. Temporal patterns in the response status of patients with systemic lupus erythematosus receiving standard of care therapy employing nonresponder imputation for missing data for 180 patients included. Green indicates complete response, yellow indicates partial response and red indicates no response

High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership.

ObjectiveDelayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1.MethodsA total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year.ResultsAt biopsy, 54 patients had UPCR <1 and 221 had UPCR ≥1. Independent of UPCR or biopsy number, a majority (92%) of patients had class III, IV, V or mixed histology. Moreover, patients with UPCR <1 and class III, IV, V, or mixed had a median activity index of 4.5 and chronicity index of 3, yet 39% of these patients had an inactive sediment. Neither anti-dsDNA nor low complement distinguished class I or II from III, IV, V or mixed in patients with UPCR <1. Of 29 patients with baseline UPCR <1 and class III, IV, V or mixed, 23 (79%) had a UPCR <0.5 at 1 year.ConclusionIn this prospective study, three-quarters of patients with UPCR <1 had histology showing class III, IV, V or mixed with accompanying activity and chronicity despite an inactive sediment or normal serologies. These data support renal biopsy at thresholds lower than a UPCR of 1