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Active and passive immunization is used in high-risk patients to prevent severe courses of COVID-19, but the impact of prophylactic neutralizing antibodies on the immune reaction to the mRNA vaccines has remained enigmatic. Here we show that CD4 T and B cell responses to Spikevax booster immunization are suppressed by the therapeutic antibodies Casirivimab and Imdevimab. B cell and T cell responses were significantly induced in controls but not in antibody-treated patients. The data indicates that humoral immunity, i. e. high levels of antibodies, negatively impacts reactive immunity, resulting in blunted cellular responses upon boosting. This argues for temporal separation of vaccination efforts; with active vaccination preferably applied before prophylactic therapeutic antibody treatment.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Linfocitos B , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Linfocitos B/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Vacunas contra la COVID-19/inmunología , SARS-CoV-2/inmunología , Persona de Mediana Edad , Masculino , Femenino , Vacunación , Adulto , Anciano , Linfocitos T CD4-Positivos/inmunología , Linfocitos T/inmunología , Inmunización Secundaria , Inmunidad Humoral , Anticuerpos Monoclonales Humanizados/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
OBJECTIVE: Reliable interpretation of imaging findings is essential for the diagnosis of axial spondyloarthritis (axSpA) and requires a high level of experience. We investigated experience-dependent differences in diagnostic accuracies using X-ray (XR), MRI and CT. METHODS: This post hoc analysis included 163 subjects with low back pain. Eighty-nine patients had axSpA, and 74 patients had other conditions (mechanical, degenerative or non-specific low back pain). Final diagnoses were established by an experienced rheumatologist before the reading sessions. Nine blinded readers (divided into three groups with different levels of experience) scored the XR, CT and MRI of the sacroiliac joints for the presence versus absence of axSpA. Parameters for diagnostic performance were calculated using contingency tables. Differences in diagnostic performance between the reader groups were assessed using the McNemar test. Inter-rater reliability was assessed using Fleiss kappa. RESULTS: Diagnostic performance was highest for the most experienced reader group, except for XR. In the inexperienced and semi-experienced group, diagnostic performance was highest for CT&MRI (78.5% and 85.3%, respectively). In the experienced group, MRI showed the highest performance (85.9%). The greatest difference in diagnostic performance was found for MRI between the inexperienced and experienced group (76.1% vs 85.9%, p=0.001). Inter-rater agreement was best for CT in the experienced group with κ=0.87. CONCLUSION: Differences exist in the learnability of the imaging modalities for axSpA diagnosis. MRI requires more experience, while CT is more suitable for inexperienced radiologists. However, diagnosis relies on both clinical and imaging information.
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Espondiloartritis Axial , Dolor de la Región Lumbar , Humanos , Reproducibilidad de los Resultados , Articulación Sacroiliaca/diagnóstico por imagen , InvestigadoresRESUMEN
Idiopathic inflammatory myopathy (IIM) is a group of rare and heterogeneous systemic diseases that manifest not only in the muscles but also in the skin, joints, and lungs. Initial symptoms can be isolated and variable and thus the diagnosis poses challenges to various specialist groups. As autoantibodies are sometimes the only specific findings that lead to the diagnosis and appropriate treatment, basic knowledge of them is essential. This article explains the available test systems, names the clinical indications necessary for the initiation of autoantibody diagnostics, provides information on the etymology, antigens, synonyms, and first descriptors, describes indirect immunofluorescence on HEp2 cells induced by myositis antibodies, and provides clinical-serological associations. The comparison of the autoantibody findings with the clinical symptoms and laboratory findings enables the identification of false positive or false negative laboratory findings in the sense of a plausibility check.
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Autoanticuerpos , Miositis , Humanos , Miositis/diagnósticoRESUMEN
OBJECTIVES: Reporting diagnostic confidence (DC) in axial spondyloarthritis (axSpA) imaging is recommended by the ASAS guidelines. Our aim was to investigate whether self-reported DC predicts diagnostic accuracy in axSpA imaging using X-ray (XR), computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: We performed a post hoc analysis including 163 patients with low back pain (89 axSpA and 56 non-axSpA). Nine blinded readers with different experience levels (inexperienced (< 1 year), semi-experienced (3-8 years) and experienced (> 12 years)) scored the sacroiliac joint images for compatibility with axSpA. DC was reported on a scale from 1 (not sure) to 10 (very sure). Mean DC scores and standard deviations were calculated for correct and incorrect responses using XR, CT, MRI, XR+MRI and CT+MRI. Differences in DC were assessed using the Mann-Whitney U test. RESULTS: DC scores were higher for correct axSpA diagnoses and differed significantly between correct and incorrect responses for all modalities (p< 0.001), with a mean DC of 7.1 ± 2.1 and 6.3 ± 2.1 for XR, 8.3 ± 1.8 and 6.7 ± 2.0 for CT, 8.1 ± 1.9 and 6.2 ± 1.9 for MRI, 8.2 ± 1.8 and 6.7 ± 1.8 for XR+MRI and 8.4 ± 1.8 and 6.8 ± 1.8 for CT+MRI, respectively. This was also the case when looking at the results by experience group, except for XR in the inexperienced group. CONCLUSION: Providing self-reported DC in radiological reports is useful information to predict diagnostic reliability in axSpA imaging.
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BACKGROUND: Type I interferons (IFN-Is) play a role in a broad range of rheumatic and musculoskeletal diseases (RMDs), and compelling evidence suggests that their measurement could have clinical value, although testing has not progressed into clinical settings. OBJECTIVE: To develop evidence-based points to consider (PtC) for the measurement and reporting of IFN-I assays in clinical research and to determine their potential clinical utility. METHODS: EULAR standardised operating procedures were followed. A task force including rheumatologists, immunologists, translational scientists and a patient partner was formed. Two systematic reviews were conducted to address methodological and clinical questions. PtC were formulated based on the retrieved evidence and expert opinion. Level of evidence and agreement was determined. RESULTS: Two overarching principles and 11 PtC were defined. The first set (PtC 1-4) concerned terminology, assay characteristics and reporting practices to enable more consistent reporting and facilitate translation and collaborations. The second set (PtC 5-11) addressed clinical applications for diagnosis and outcome assessments, including disease activity, prognosis and prediction of treatment response. The mean level of agreement was generally high, mainly in the first PtC set and for clinical applications in systemic lupus erythematosus. Harmonisation of assay methodology and clinical validation were key points for the research agenda. CONCLUSIONS: IFN-I assays have a high potential for implementation in the clinical management of RMDs. Uptake of these PtC will facilitate the progress of IFN-I assays into clinical practice and may be also of interest beyond rheumatology.
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Enfermedades Musculoesqueléticas , Reumatología , HumanosRESUMEN
BACKGROUND: Type I interferons (IFN-I) contribute to a broad range of rheumatic and musculoskeletal diseases (RMDs). Compelling evidence suggests that the measurement of IFN-I pathway activation may have clinical value. Although several IFN-I pathway assays have been proposed, the exact clinical applications are unclear. We summarise the evidence on the potential clinical utility of assays measuring IFN-I pathway activation. METHODS: A systematic literature review was conducted across three databases to evaluate the use of IFN-I assays in diagnosis and monitor disease activity, prognosis, response to treatment and responsiveness to change in several RMDs. RESULTS: Of 366 screened, 276 studies were selected that reported the use of assays reflecting IFN-I pathway activation for disease diagnosis (n=188), assessment of disease activity (n=122), prognosis (n=20), response to treatment (n=23) and assay responsiveness (n=59). Immunoassays, quantitative PCR (qPCR) and microarrays were reported most frequently, while systemic lupus erythematosus (SLE), rheumatoid arthritis, myositis, systemic sclerosis and primary Sjögren's syndrome were the most studied RMDs. The literature demonstrated significant heterogeneity in techniques, analytical conditions, risk of bias and application in diseases. Inadequate study designs and technical heterogeneity were the main limitations. IFN-I pathway activation was associated with disease activity and flare occurrence in SLE, but their incremental value was uncertain. IFN-I pathway activation may predict response to IFN-I targeting therapies and may predict response to different treatments. CONCLUSIONS: Evidence indicates potential clinical value of assays measuring IFN-I pathway activation in several RMDs, but assay harmonisation and clinical validation are urged. This review informs the EULAR points to consider for the measurement and reporting of IFN-I pathway assays.
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Interferón Tipo I , Lupus Eritematoso Sistémico , Enfermedades Musculoesqueléticas , Miositis , Humanos , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/etiología , Lupus Eritematoso Sistémico/diagnósticoRESUMEN
OBJECTIVES: To systematically review the literature for assay methods that aim to evaluate type I interferon (IFN-I) pathway activation and to harmonise-related terminology. METHODS: Three databases were searched for reports of IFN-I and rheumatic musculoskeletal diseases. Information about the performance metrics of assays measuring IFN-I and measures of truth were extracted and summarised. A EULAR task force panel assessed feasibility and developed consensus terminology. RESULTS: Of 10 037 abstracts, 276 fulfilled eligibility criteria for data extraction. Some reported more than one technique to measure IFN-I pathway activation. Hence, 276 papers generated data on 412 methods. IFN-I pathway activation was measured using: qPCR (n=121), immunoassays (n=101), microarray (n=69), reporter cell assay (n=38), DNA methylation (n=14), flow cytometry (n=14), cytopathic effect assay (n=11), RNA sequencing (n=9), plaque reduction assay (n=8), Nanostring (n=5), bisulphite sequencing (n=3). Principles of each assay are summarised for content validity. Concurrent validity (correlation with other IFN assays) was presented for n=150/412 assays. Reliability data were variable and provided for 13 assays. Gene expression and immunoassays were considered most feasible. Consensus terminology to define different aspects of IFN-I research and practice was produced. CONCLUSIONS: Diverse methods have been reported as IFN-I assays and these differ in what elements or aspects of IFN-I pathway activation they measure and how. No 'gold standard' represents the entirety of the IFN pathway, some may not be specific for IFN-I. Data on reliability or comparing assays were limited, and feasibility is a challenge for many assays. Consensus terminology should improve consistency of reporting.
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Interferón Tipo I , Enfermedades Musculoesqueléticas , Enfermedades Reumáticas , Humanos , Reproducibilidad de los Resultados , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/etiología , Enfermedades Reumáticas/diagnóstico , Comités ConsultivosRESUMEN
OBJECTIVE: To determine whether repeated, dose-intensified mRNA vaccinations against COVID-19 increase humoral immunity in previously low-responding patients with autoimmune rheumatic diseases (AIRD), including rituximab-treated and B cell depleted patients. METHODS: Of 308 AIRD patients receiving basic immunization, 98 had a low serological response against SARS-CoV-2 with a neutralizing capacity of < 70% using surrogate neutralization assay. 38 patients received a third vaccination with 30 µg BNT162b2 16 weeks after second vaccination. If neutralizing serum capacity was below 70% four weeks after the last vaccination, then the fourth vaccination (n = 19) and the fifth (n = 4) vaccination with 100 µg mRNA-1273 took place eight weeks after the last vaccination. RESULTS: Each of the three booster vaccinations resulted in a significant increase of mean serum neutralizing capacity (3rd: Δ = 42%, p < 0.001; 4th: Δ = 19%, p = 0.049 and 5th: Δ = 51%, p = 0.043) and produced a significant proportion of high-responders (3rd: 34%; 4th: 32% and 5th: 75%). Low B cell counts (p = 0.047), lower previous antibody response (p < 0.001) and rituximab therapy (p = 0.021) were negatively associated with successful response to the third but not to the fourth vaccination. Remarkably, substantial increases in neutralization capacity of up to 99% were observed after repeated vaccinations in B cell depleted patients. CONCLUSION: AIRD patients with low humoral response benefited from up to three repeated dose-intensified mRNA booster vaccinations - despite low B cell count and previous rituximab therapy. Each additional vaccination substantially reduced the number of low-responding, vulnerable patients.
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Enfermedades Autoinmunes , COVID-19 , Enfermedades Reumáticas , Humanos , Inmunidad Humoral , Vacunas contra la COVID-19 , Vacuna BNT162 , Rituximab , SARS-CoV-2 , Vacunación , ARN Mensajero , Anticuerpos Antivirales , Anticuerpos NeutralizantesRESUMEN
In this retrospective study, PET/CT data from 59 patients with suspected giant cell arteritis (GCA) were reviewed using the Deauville criteria to determine an optimal cut-off between PET positivity and negativity. Seventeen standardised vascular regions were analysed per patient by three investigators blinded to clinical information. Statistical analysis included ROC curves with areas under the curve (AUC), Cohen's and Fleiss' kappa (κ) to calculate sensitivity, specificity, accuracy, and agreement. According to final clinician's diagnosis and the revised 2017 ACR criteria GCA was confirmed in 29 of 59 (49.2 %) patients. With a diagnostic cut-off ≥ 4 (highest tracer uptake of a vessel wall exceeds liver uptake) for PET positivity, all investigators achieved high accuracy (range, 89.8-93.2%) and AUC (range, 0.94-0.97). Sensitivity and specificity ranged from 89.7-96.6% and 83.3-96.7%, respectively. Agreement between the three investigators suggested 'almost perfect agreement' (Fleiss' κ = 0.84) A Deauville score of ≥4 as threshold for PET positivity yielded excellent results with high accuracy and almost perfect inter-rater agreement, suggesting a standardized, reproducible, and reliable score in diagnosing GCA. However, the small sample size and reference standard could lead to biases. Therefore, verification in a multicentre study with a larger patient cohort and prospective setting is needed.
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Systemic Sclerosis (SSc) is a clinically heterogeneous disease that includes an upregulation of type I interferons (IFNs). The aim of this observational study was to investigate the IFN-regulated protein Sialic Acid−Binding Ig-like Lectin 1 (SIGLEC-1) as a biomarker for disease phenotype, therapeutic response, and differential diagnosis in SSc. Levels of SIGLEC-1 expression on monocytes of 203 SSc patients were determined in a cross-sectional and longitudinal analysis using multicolor flow cytometry, then compared to 119 patients with other rheumatic diseases and 13 healthy controls. SSc patients higher SIGLEC-1 expression on monocytes (2097.94 ± 2134.39) than HCs (1167.45 ± 380.93; p = 0.49), but significantly lower levels than SLE (8761.66 ± 8325.74; p < 0.001) and MCTD (6414.50 ± 1846.55; p < 0.001) patients. A positive SIGELC-1 signature was associated with reduced forced expiratory volume (p = 0.007); however, we were unable to find an association with fibrotic or vascular disease manifestations. SIGLEC-1 remained stable over time and was independent of changes in immunosuppressive therapy. However, SIGLEC-1 is suitable for differentiating SSc from other connective tissue diseases. SIGLEC-1 expression on monocytes can be useful in the differential diagnosis of connective tissue disease but not as a biomarker for SSc disease manifestations or activity.
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OBJECTIVE: The level of neutralising capacity against Omicron BA.1 and BA.2 after third COVID-19 vaccination in patients on paused or continuous methotrexate (MTX) therapy is unclear. METHODS: In this observational cohort study, neutralising serum activity against SARS-CoV-2 wild-type (Wu01) and variant of concern Omicron BA.1 and BA.2 were assessed by pseudovirus neutralisation assay before, 4 and 12 weeks after mRNA booster immunisation in 50 rheumatic patients on MTX, 26 of whom paused the medication. 44 non-immunosuppressed persons (NIP) served as control group. RESULTS: While the neutralising serum activity against SARS-CoV-2 Wu01 and Omicron variants increased 67-73 fold in the NIP after booster vaccination, the serum activity in patients receiving MTX increased only 20-23 fold. Patients who continued MTX treatment during vaccination had significantly lower neutralisation against all variants at weeks 4 and 12 compared with patients who paused MTX and the control group, except for BA.2 at week 12. Patients who paused MTX reached comparably high neutralising capacities as NIP, except for Wu01 at week 12. The duration of the MTX pause after-not before-was associated with a significantly higher neutralisation capacity against all three variants, with an optimal duration at 10 days after vaccination. CONCLUSION: Patients pausing MTX after COVID-19 booster showed a similar vaccine response to NIP. Patients who continued MTX demonstrated an impaired response indicating a potentially beneficial second booster vaccination. Our data also suggest that a 1 week MTX break is sufficient if the last administration of MTX occurs 1-3 days before vaccination.
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Antirreumáticos , COVID-19 , Vacunas , Antirreumáticos/uso terapéutico , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Metotrexato/uso terapéutico , SARS-CoV-2 , VacunaciónRESUMEN
OBJECTIVES: Inflammatory rheumatic and musculoskeletal diseases (iRMDs) are associated with increased systemic bone loss that is mediated by chronic inflammation, treatment with glucocorticoids (GCs) and other factors. Our objective was to analyse the impact of variables that influence osteoporosis (OP) in patients with iRMD treated with GC. METHODS: Rh-GIOP (acronyme) is a prospective observational cohort study investigating bone health in consecutive patients with iRMD and current or prior GC treatment. We present an analysis of the patients' baseline data here. Bone mineral density (BMD) measured by dual X-ray absorptiometry was the primary outcome. Multivariable linear regression models were performed to identify variables associated with BMD. RESULTS: Data from 1066 patients with iRMD were analysed. GC doses of <5 mg prednisone equivalent per day, cumulative dose and duration of GC therapy were not associated with negative effects on BMD. Dosages of ≥5 mg/day lost their negative association with BMD after adjustment for confounders. When subanalysing patients with exactly 5 mg/day, no negative effect was seen. For patients with rheumatoid arthritis (RA), GC doses of >7.5 mg/day showed a negative association with BMD overall, but this effect seemed to be specific only to patients with moderate or high disease activity (Disease Activity Score 28-C reactive protein >3.2). CONCLUSIONS: GCs of ≤5 mg/day did not seem to be associated with a reduction of BMD in patients with iRMD and current or prior exposure to GC. This is most likely due to the dampening of inflammation by GC, which exerts a mitigating effect on the risk of OP. In RA, current GC doses of >7.5 mg/day were negatively associated with BMD, but only in patients with moderate to high disease activity. TRIAL REGISTRATION NUMBER: NCT02719314.
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OBJECTIVES: To investigate the performance of dual-energy CT (DECT)-generated iodine maps (iMap) and CT subtraction (CT-S) in the detection of synovitis, tenosynovitis, and peritendonitis/paratenonitis compared to magnetic resonance imaging (MRI) using musculoskeletal ultrasound (MSUS) as standard of reference. METHODS: This IRB-approved prospective study consecutively investigated patients with undifferentiated arthritis. All patients underwent MSUS, MRI and contrast-enhanced DECT of the hand; from the latter conventional CT-S, image-based iMap (iMap-I) and raw data-based iMap (iMap-RD) were reconstructed. CT and MRI datasets were scored for synovitis and tenosynovitis/paratenonitis applying the modified Rheumatoid Arthritis MRI Score (RAMRIS). Sensitivity, specificity, and diagnostic accuracy were calculated. Non-inferiority was tested using the one-tailed McNemar test. Correlation of sum scores was assessed using Pearson's test. Interreader reliability was assessed using Cohen's kappa. RESULTS: Overall, 33 patients were included. MSUS was positive for synovitis and tenosynovitis/paratenonitis in 28 patients with a sum score of 6.91. Excellent correlation with MSUS was shown for CT-S (sum score 6.38; r = 0.91), iMap-RD (sum score 9.74; r = 0.82), MRI (sum score 12.70; r = 0.85), and iMap-I (sum score 6.94; r = 0.50). CT-S had the highest diagnostic accuracy of 83%, followed by iMap-I (78%), MRI (75%), and iMap-RD (74%). All modalities showed non-inferiority. Reader agreement was good for CT-S and MRI (κ = 0.62; 0.64) and fair for iMap-RD and iMap-I (κ = 0.31; 0.37). CONCLUSION: CT-S and iMap allow highly standardized arthritis imaging and are suitable for clinical practice. MSUS still has the highest availability for arthritis imaging and served as gold standard for this study. KEY POINTS: ⢠CT subtraction, iodine map with dual-energy CT, and MRI showed non-inferiority to musculoskeletal ultrasound. ⢠MRI was the most sensitive but least specific imaging technique compared with CT subtraction and dual-energy CT. ⢠CT subtraction showed the best correlation with musculoskeletal ultrasound.
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Artritis Reumatoide , Yodo , Sinovitis , Tenosinovitis , Humanos , Imagen por Resonancia Magnética/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Sinovitis/diagnóstico por imagen , Sinovitis/patología , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE: To study the effect of methotrexate (MTX) and its discontinuation on the humoral immune response after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD). METHODS: In this retrospective study, neutralising SARS-CoV-2 antibodies were measured after second vaccination in 64 patients with AIRD on MTX therapy, 31 of whom temporarily paused medication without a fixed regimen. The control group consisted of 21 patients with AIRD without immunosuppressive medication. RESULTS: Patients on MTX showed a significantly lower mean antibody response compared with patients with AIRD without immunosuppressive therapy (71.8% vs 92.4%, p<0.001). For patients taking MTX, age correlated negatively with immune response (r=-0.49; p<0.001). All nine patients with antibody levels below the cut-off were older than 60 years. Patients who held MTX during at least one vaccination showed significantly higher mean neutralising antibody levels after second vaccination, compared with patients who continued MTX therapy during both vaccinations (83.1% vs 61.2%, p=0.001). This effect was particularly pronounced in patients older than 60 years (80.8% vs 51.9%, p=0.001). The impact of the time period after vaccination was greater than of the time before vaccination with the critical cut-off being 10 days. CONCLUSION: MTX reduces the immunogenicity of SARS-CoV-2 vaccination in an age-dependent manner. Our data further suggest that holding MTX for at least 10 days after vaccination significantly improves the antibody response in patients over 60 years of age.
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Enfermedades Autoinmunes , COVID-19 , Enfermedades Reumáticas , Anciano , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunogenicidad Vacunal , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Reumáticas/tratamiento farmacológico , SARS-CoV-2 , VacunaciónRESUMEN
OBJECTIVE: To evaluate sialic acid binding Ig-like lectin 1 (SIGLEC1) expression on monocytes by flow cytometry as a type I interferon biomarker in idiopathic inflammatory myopathies (IIM). METHODS: We performed a retrospective analysis of adult and paediatric patients with the diagnosis of IIM. SIGLEC1 expression was assessed by flow cytometry and was compared with Physician Global Assessment or Childhood Myositis Assessment Scale disease activity scores. Mann Whitney U test and receiver operating characteristic curves were used for cross-sectional data analysis (n=96), two-level mixed-effects linear regression model for longitudinal analyses (n=26, 110 visits). Response to treatment was analysed in 14 patients within 12 months, using Wilcoxon test. SIGLEC1 was compared with interferon-stimulated gene 15/MxA status by immunohistochemical staining of muscle biopsies (n=17). RESULTS: 96 patients with adult (a) and juvenile (j) dermatomyositis (DM, n=38), antisynthetase syndrome (AS, n=19), immune-mediated necrotising myopathy (IMNM, n=8), inclusion body myositis (IBM, n=9) and overlap myositis (n=22) were included. SIGLEC1 distinguished significantly between active and inactive disease with an area under the curve of 0.92 (95% CI 0.83 to 1) in DM and correlated with disease activity longitudinally (aDM: standardised beta=0.54, p<0.001; jDM: standardised beta=-0.70, p<0.001). Response to treatment in DM was associated with a decreasing SIGLEC1 (p<0.01, Wilcoxon test). SIGLEC1 was found upregulated in 8 of 19 patients with AS, 2 of 9 patients with IBM but not in IMNM. CONCLUSION: SIGLEC1 is a candidate biomarker to assess type I interferon activity in IIM and proved useful for monitoring disease activity and response to treatment in juvenile and adult DM.
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Dermatomiositis , Interferón Tipo I , Miositis , Lectina 1 Similar a Ig de Unión al Ácido Siálico , Adulto , Niño , Estudios Transversales , Dermatomiositis/diagnóstico , Dermatomiositis/patología , Humanos , Miositis/diagnóstico , Estudios Retrospectivos , Lectina 1 Similar a Ig de Unión al Ácido Siálico/genéticaRESUMEN
OBJECTIVES: To evaluate and compare the diagnostic accuracy of SIGLEC1, a surrogate marker of type I IFN, with established biomarkers in an inception cohort of systemic lupus erythematosus (SLE). METHODS: SIGLEC1 was analysed by flow cytometry in 232 patients referred to our institution with suspected SLE between October 2015 and September 2020. RESULTS: SLE was confirmed in 76 of 232 patients (32.8 %) according to the 2019 EULAR/ACR classification criteria and their SIGLEC1 values were significantly higher compared with patients without SLE (P <0.0001). A sensitivity of 98.7 %, a specificity of 82.1 %, a negative predictive value (NPV) of 99.2 % and a positive predictive value (PPV) of 72.8 % were calculated for SIGLEC1. Adjusted to the highest reported prevalence of SLE, the NPV and PPV were >99.9 % and 0.1 %, respectively. Using receiver operating characteristic (ROC) analysis and DeLong testing, the area under the curve (AUC) for SIGLEC1 (AUC = 0.95) was significantly higher than for ANA (AUC = 0.88, P = 0.031), C3 (AUC = 0.83, P = 0.001) and C4 (AUC = 0.83, P = 0.002) but not for anti-dsDNA antibodies (AUC = 0.90, P = 0.163). CONCLUSION: IFN-I pathway activation is detectable in almost all newly diagnosed SLE patients. Thus, a negative test result for SIGLEC1 is powerful to exclude SLE in suspected cases.