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1.
J Autoimmun ; : 102338, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31570253

RESUMO

BACKGROUND: Progressive fibrosing interstitial lung disease (ILD) is rarely associated with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). This study focused on the outcomes of ILD patients with associated AAV (AAV-ILD). METHODS: AAV-ILD (cases: microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) with ILD) were compared to AAV patients without ILD (controls). ILD was defined as a usual interstitial pneumonia (UIP) or non-specific interstitial pneumonia (NSIP) pattern. Two controls were matched to each case for age (>or ≤65 years), ANCA status (PR3-or MPO-positive) and creatininemia (≥or <150 µmol/L). RESULTS: Sixty-two cases (89% MPO-ANCA+) were included. Median age at AAV diagnosis was 66 years. ILD (63% UIP), was diagnosed before (52%) or simultaneously (39%) with AAV. Cases versus 124 controls less frequently had systemic vasculitis symptoms. One-, 3- and 5-year overall survival rates, respectively, were: 96.7%, 80% and 66% for cases versus 93.5%, 89.6% and 83.8% for controls (p = 0.008). Multivariate analyses retained age >65 years (hazard ratio (HR) 4.54; p < 0.001), alveolar haemorrhage (HR 2.25; p = 0.019) and UIP (HR 2.73; p = 0.002), but not immunosuppressant use, as factors independently associated with shorter survival. CONCLUSION: For AAV-ILD patients, only UIP was associated with poorer prognosis. Immunosuppressants did not improve the AAV-ILD prognosis. But in analogy to idiopathic pulmonary fibrosis, anti-fibrosing agents might be useful and should be assessed in AAV-ILD patients with a UIP pattern.

2.
Autoimmun Rev ; : 102405, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31648043

RESUMO

With advances in our understanding of the pathogenesis of large vessel vasculitides, we recognise the persistence of inflammation in large vessels, sometimes despite therapy to control clinical symptoms. Achieving an early diagnosis and establishing the extent of disease are important steps in improving our management of these diseases. Imaging is playing an increasing role in the assessment of these patients from diagnosis to prognosis. We review the current and potential role of two important and potentially complementary imaging techniques of magnetic resonance angiography and 18F-fluorodeoxyglucose positron emission tomography in the evaluation of patients with giant cell arteritis and Takayasu arteritis.

5.
Autoimmun Rev ; 18(7): 714-720, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059846

RESUMO

BACKGROUND: Age at onset of large-vessel vasculitis (LVV) is commonly used to distinguish giant cell arteritis (GCA) and Takayasu arteritis (TA). However, LVV between age 50 and 60 years may be difficult to classify. METHODS: We conducted a retrospective study including LVV aged between 50 and 60 years at onset (LVV50-60, cases) and compared them to LVV aged over 60 years (LVV>60, controls). LVV was defined histologically and/or morphologically. Controls fulfilled ACR 1990 criteria for GCA or presented isolated aortitis. RESULTS: We included 183 LVV50-60 and 183 gender-matched LVV>60. LVV50-60 had more frequent peripheral limb manifestations (23 vs. 5%), and less frequent cephalic (73 vs. 90%) and ocular signs (17 vs. 27%) than LVV>60. Compared to LVV>60, CT angiography and PET/CT scan were more frequently abnormal in LVV50-60 (74 vs. 38%, and 90 vs. 72%, respectively), with aorta being more frequently involved (78 vs. 47%). By multivariate analysis, absence of cephalic symptoms, presence of peripheral limb ischemia and aorta involvement, and increased CRP level were significantly associated with LVV50-60 presentation compared to LVV>60. At last follow-up, compared to LVV>60, LVV50-60 received significantly more lines of treatment (2 vs. 1), more frequent biologics (12 vs. 3%), had more surgery (10 vs. 0%), and had higher prednisone dose (8.8 vs. 6.5 mg/d) at last follow-up, CONCLUSION: LVV onset between 50 and 60 years identifies a subset of patients with more frequent aorta and peripheral vascular involvement and more refractory disease compared to patients with LVV onset after 60.


Assuntos
Arterite de Células Gigantes/epidemiologia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Front Immunol ; 10: 538, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30967870

RESUMO

Systemic Lupus Erythematosus (SLE) is a common and devastating autoimmune disease, characterized by a dysregulated adaptive immune response against intracellular antigens, which involves both autoreactive T and B cells. In SLE, mainly intracellular autoantigens generate autoantibodies and these assemble into immune complexes and activate the classical pathway of the complement system enhancing inflammation. Matrix metalloproteinase-9 (MMP-9) levels have been investigated in the serum of SLE patients and in control subjects. On the basis of specific studies, it has been suggested to treat SLE patients with MMP inhibitors. However, some of these inhibitors induce SLE. Analysis of LPR-/-MMP-9-/- double knockout mice suggested that MMP-9 plays a protective role in autoantigen clearance in SLE, but the effects of MMP-9 on immune complexes remained elusive. Therefore, we studied the role of MMP-9 in the clearance of autoantigens, autoantibodies and immune complexes and demonstrated that the lack of MMP-9 increased the levels of immune complexes in plasma and local complement activation in spleen and kidney in the LPR-/- mouse model of SLE. In addition, we showed that MMP-9 dissolved immune complexes from plasma of lupus-prone LPR-/-/MMP-9-/- mice and from blood samples of SLE patients. Surprisingly, autoantigens incorporated into immune complexes, but not immunoglobulin heavy or light chains, were cleaved by MMP-9. We discovered Apolipoprotein-B 100 as a new substrate of MMP-9 by analyzing the degradation of immune complexes from human plasma samples. These data are relevant to understand lupus immunopathology and side-effects observed with the use of known drugs. Moreover, we caution against the use of MMP inhibitors for the treatment of SLE.

8.
Arthritis Rheumatol ; 71(8): 1329-1338, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30835950

RESUMO

OBJECTIVE: This study was undertaken to evaluate glucocorticoid dosages and serologic findings in patients with giant cell arteritis (GCA) flares. METHODS: Patients with GCA were randomly assigned to receive double-blind dosing with either subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week prednisone taper (TCZ-QW + Pred-26), every-other-week TCZ plus 26-week prednisone taper (TCZ-Q2W + Pred-26), placebo plus 26-week prednisone taper (PBO + Pred-26), or placebo plus 52-week prednisone taper (PBO + Pred-52). Outcome measures were prednisone dosage, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare. RESULTS: One hundred patients received TCZ-QW + Pred-26, 49 received TCZ-Q2W + Pred-26, 50 received PBO + Pred-26, and 51 received PBO + Pred-52. Of the 149 TCZ-treated patients, 36 (24%) experienced flare, 23 (64%) of whom were still receiving prednisone (median dosage 2.0 mg/day). Among 101 PBO + Pred-treated patients, 59 (58%) experienced flare, 45 (76%) of whom were receiving prednisone (median dosage 5.0 mg/day). Many flares occurred while patients were taking >10 mg/day prednisone: 9 (25%) in the TCZ groups and 13 (22%) in the placebo groups. Thirty-three flares (92%) in TCZ-treated groups and 20 (34%) in PBO + Pred-treated groups occurred with normal CRP levels. More than half of the PBO + Pred-treated patients had elevated CRP levels without flares. Benefits of the TCZ and prednisone combination over prednisone alone for remission induction were apparent by 8 weeks. CONCLUSION: Most GCA flares occurred while patients were still receiving prednisone. Acute-phase reactant levels were not reliable indicators of flare in patients treated with TCZ plus prednisone or with prednisone alone. The addition of TCZ to prednisone facilitates earlier GCA control.

10.
Arthritis Rheumatol ; 71(6): 952-963, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30666823

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of belimumab as adjunctive therapy to maintain remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: In this multicenter, double-blind, placebo-controlled study, patients with AAV (ages ≥18 years) were randomized 1:1 to receive azathioprine (2 mg/kg/day), low-dose oral glucocorticoids (≤10 mg/day), and either intravenous belimumab (10 mg/kg) or placebo, following remission induction with rituximab or cyclophosphamide along with glucocorticoids. The primary end point was time to first protocol-specified event (PSE), with first PSE defined as a Birmingham Vasculitis Activity Score (BVAS) of ≥6, presence of ≥1 major BVAS item, or receipt of prohibited medications for any reason, resulting in treatment failure (adjusted for ANCA type [proteinase 3 (PR3) or myeloperoxidase (MPO)], disease stage at induction, and induction regimen). Vasculitis relapse was defined as the PSE of either a BVAS activity score of ≥6 or receipt of prohibited medications for vasculitis. Changes in treatment practice led to truncation of the study population from ~300 patients to ~100 patients. RESULTS: The intent-to-treat population totaled 105 patients with AAV, of whom 52 (40 with PR3-ANCAs, 12 with MPO-ANCAs) received placebo and 53 (41 with PR3-ANCAs, 12 with MPO-ANCAs) received belimumab; 27 of the patients were in rituximab-induced disease remission, while 78 were in cyclophosphamide-induced disease remission at baseline. Compared with placebo, treatment with belimumab did not reduce the risk of a PSE (adjusted hazard ratio [HR] 1.07, 95% confidence interval [95% CI] 0.44-2.59; P = 0.884) or vasculitis relapse (adjusted HR 0.88, 95% CI 0.29-2.65; P = 0.821). The overall rate of PSEs was low (11 [21.2%] of 52 patients receiving placebo, 10 [18.9%] of 53 patients receiving belimumab). Vasculitis relapse in the placebo group (n = 8) occurred independent of the induction regimen, disease stage, or ANCA type. All vasculitis relapses in the belimumab group (n = 6) occurred in patients who had PR3-ANCA-associated vasculitis with cyclophosphamide-induced disease remission. Adverse events occurred in 49 (92.5%) of 53 patients receiving belimumab and 43 (82.7%) of 52 patients receiving placebo, with no new safety concerns. CONCLUSION: Belimumab plus azathioprine and glucocorticoids for the maintenance of remission in AAV did not reduce the risk of relapse.

11.
Ann Rheum Dis ; 78(3): 399-405, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30612116

RESUMO

OBJECTIVES: Cyclophosphamide induction regimens are effective for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but are associated with infections, malignancies and infertility. Mycophenolate mofetil (MMF) has shown high remission rates in small studies of AAV. METHODS: We conducted a randomised controlled trial to investigate whether MMF was non-inferior to cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients were randomly assigned to MMF or pulsed cyclophosphamide. All patients received the same oral glucocorticoid regimen and were switched to azathioprine following remission. The primary endpoint was remission by 6 months requiring compliance with the tapering glucocorticoid regimen. Patients with an eGFR <15 mL/min were excluded from the study. RESULTS: At baseline, ANCA subtype, disease activity and organ involvement were similar between groups. Non-inferiority was demonstrated for the primary remission endpoint, which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in the cyclophosphamide group (risk difference 5.7%, 90% CI -7.5% to 19%). Following remission, more relapses occurred in the MMF group (23 patients, 33%) compared with the cyclophosphamide group (13 patients, 19%) (incidence rate ratio 1.97, 95% CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and 48% of the MMF group. Serious infections were similar between groups (26% MMF group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3). CONCLUSION: MMF was non-inferior to cyclophosphamide for remission induction in AAV, but resulted in higher relapse rate. TRIAL REGISTRATION NUMBER: NCT00414128.

12.
Best Pract Res Clin Rheumatol ; 32(1): 63-82, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-30526899

RESUMO

Imaging plays an increasing role for confirming a suspected diagnosis of giant cell arteritis (GCA) or Takayasu arteritis (TAK). Ultrasound, magnetic resonance imaging (MRI), and computed tomography demonstrate a homogeneous, most commonly concentric, arterial wall thickening. 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) displays increased FDG uptake of inflamed artery walls delineating increased metabolism. Ultrasound and MRI are recommended to be the initial imaging modalities in cranial GCA and TAK, respectively. Extracranial disease can be confirmed by all four modalities, particularly by PET in case of inflammation of unknown origin. If the diagnosis remains uncertain, additional investigations including biopsy and/or additional imaging are recommended. Imaging should be performed by a trained specialist using appropriate operational procedures and settings with appropriate equipment. Further research is necessary on the role of imaging for disease monitoring. This review will discuss advantages and disadvantages of imaging modalities in the diagnosis of vasculitis.


Assuntos
Imagem por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Vasculite Sistêmica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Humanos , Vasculite Sistêmica/patologia
13.
Medicine (Baltimore) ; 97(43): e12909, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30412093

RESUMO

BACKGROUND: Spontaneous remission is common in patients with undiagnosed classic fever of unknown origin (FUO). Although identifying reliable predictors of spontaneous remission in such diagnostically challenging cases could improve their management strategies, few studies have assessed such clinical factors. Recently, studies have reported that F-fluorodeoxyglucose positron emission tomography (F-FDG PET) alone and integrated with computed tomography (PET/CT) were useful in localizing the source of FUO. In this systematic review and meta-analysis, we assessed the association of results of these imaging modalities with spontaneous remission in patients with classic FUO. METHODS: We searched PubMed and Scopus from inception until June 30, 2018, and studies that evaluated the PET or PET/CT results of ≥10 adult or adolescent patients with classic FUO who were followed up for at least 3 months were included. At least 2 investigators extracted data and rated quality using the QUIPS-2 tool. We used a random-effects meta-analysis to calculate summary risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Nine studies of PET/CT results (418 patients) and 4 studies of standalone PET results (128 patients) were eligible. None explicitly specified the incidence of spontaneous remission as the primary or secondary outcomes of interest. The risk of bias was considered high in all studies because patients received subsequent diagnostic workup based on imaging results. Patients with negative PET/CT results were significantly more likely to present with spontaneous regression than those with positive results (summary RR = 5.6; 95% CI: 3.4-9.2; P < .001; I = 0%). In contrast, no significant association was found between standalone PET results and spontaneous remission. The random-effects study-level meta-regression found that PET/CT results [relative RR (rRR) = 7.4; 95% CI: 2.5-21.3; P = .002], compared with standalone PET results, and publication year (rRR = 1.2 per 1 year; 95% CI: 1.0-1.3; P = .013) were significantly associated with spontaneous remission. CONCLUSION: Limited data suggest that undiagnosed classic FUO patients with negative PET/CT results had a high likelihood of spontaneous remission after a series of unsuccessful investigations for fever workup. Prospective studies should validate these results.


Assuntos
Febre de Causa Desconhecida/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Avaliação de Resultados (Cuidados de Saúde)/tendências , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Viés , Febre de Causa Desconhecida/etiologia , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Remissão Espontânea , Estudos Retrospectivos , Adulto Jovem
14.
J Cell Mol Med ; 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30358100

RESUMO

Gelatin zymography analysis is a sensitive method and commonly used to characterize and quantify the presence of the gelatinases (MMP-2 and MMP-9) in biological samples. In human plasma samples from healthy controls and systemic lupus erythematosus (SLE) patients, we observed a gelatinolytic molecule at 80 kDa, suggestive for activated human MMP-9. However, by developing and using the EDTA/gelatin zymography method and after purification of the 80 kDa entity, we proved that this molecule was the C1s subunit of the complement system. The zymolytic capacity of C1s was validated and found to be enhanced, in the absence of calcium and in the presence of EDTA. Our findings indicate that for correct identification of gelatinolytic proteins in complex biological samples the use of EDTA/gelatin zymography for enzyme development is advised. In addition, by quantification of EDTA/gelatin zymography analysis and ELISA, we observed that the levels of C1s were higher in plasma and immune complexes of SLE patients than of healthy individuals. Therefore, our data imply that C1s may become a marker for the diagnosis of SLE.

15.
RMD Open ; 4(2): e000661, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30116555

RESUMO

Objective: As rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPAs) are not routinely tested in idiopathic inflammatory myositis (IIM), little is known about their prevalence and clinical implications in this patient group. In antisynthetase syndrome (ASS), presence of ACPA is reportedly associated with more severe and erosive arthritis. We aim to retrospectively determine the prevalence of RF and ACPA in a cross-sectional cohort of 121 patients diagnosed with IIM and to assess clinical associations. Methods: Serum samples from 121 patients diagnosed with polymyositis (n=30), dermatomyositis (n=41), ASS (n=37), inclusion body myositis (n=1), necrotising autoimmune myopathy (n=5) or overlap myositis (n=7) were analysed. RF was evaluated by nephelometry (Immage 800, Beckman-Coulter); anti-CCP antibodies were identified using fluoro enzyme immunoassays (Immuno-Cap 250, Thermo Fisher). Values above 40 IU/mL and 7 U/mL were considered positive for RF and ACPA, respectively. Results: The prevalence of RF and ACPA was 9.09% and 4.96%, respectively. No significant differences were observed between RF/ACPA positive versus negative patients. There was a numerical trend for RF-positive IIM patients to be older and have lower forced expiratory volume in 1 s levels. Conclusions: RF and ACPA are prevalent in IIM, although we detected a lower prevalence than reported in previous studies. Presence of these antibodies in patients with IIM patients is not clinically relevant in our cohort.

17.
Autoimmun Rev ; 17(6): 533-540, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29526634

RESUMO

Solid phase assays (SPAs) and automated microscope systems are increasingly used to screen for antinuclear antibodies (ANAs). The goal of this study was to evaluate the performance of three automated ANA screening assays; NOVA Lite HEp-2 using NOVA View® (NV, Inova Diagnostics), an automated indirect immunofluorescence method, EliA™ CTD Screen (Fluorescence Enzyme Immunoassay, FEIA; Thermo Fisher) and QUANTA Flash® CTD Screen Plus (Chemiluminescence immunoassay, CIA; Inova Diagnostics). The assays were performed on 480 diagnostic samples from patients with an ANA-associated rheumatic disease (AARD; systemic lupus erythematosus, primary Sjögren's syndrome, systemic sclerosis, inflammatory myopathy, mixed connective tissue disease) and on 767 samples from diseased and healthy controls. Using cut-offs proposed by the manufacturers, the sensitivity was 95%, 80.5% and 86% for NV, FEIA and CIA, respectively. The corresponding specificity was 61% (NV), 97.5% (FEIA) and 88% (CIA). The sensitivity associated with a specificity of ~95% was 79%, 82% and 78% for NV, FEIA, and CIA, respectively. Receiver operating characteristics (ROC) curve analysis revealed no differences in area under the curve (AUC) between the 3 assays when all diseases were grouped. For Sjögren's syndrome, the AUC was higher for SPAs than for NV, whereas for systemic sclerosis, the AUC was higher for NV than for CIA. For all assays, the likelihood ratio for AARD increased with increasing antibody levels and for double positivity of NV with SPA. In conclusion, the performance of automated SPA and IIF was assay- and disease-dependent. Taking into account antibody levels and combining IIF with SPA adds value.


Assuntos
Anticorpos Antinucleares/análise , Programas de Rastreamento , Anticorpos Antinucleares/imunologia , Automação Laboratorial/instrumentação , Técnica Indireta de Fluorescência para Anticorpo/instrumentação , Técnica Indireta de Fluorescência para Anticorpo/métodos , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Programas de Rastreamento/instrumentação , Programas de Rastreamento/métodos , Doença Mista do Tecido Conjuntivo/diagnóstico , Escleroderma Sistêmico/diagnóstico , Sensibilidade e Especificidade , Síndrome de Sjogren/diagnóstico
18.
Clin Rheumatol ; 37(7): 1977-1982, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29476353

RESUMO

Increasing evidence supports a relation of some occupational exposures to systemic sclerosis pathogenesis. We aimed to evaluate occupational exposure and clinical characteristics in male patients with systemic sclerosis followed in two Belgian academic hospitals. One hundred and three male patients, included in the Belgian Systemic Sclerosis Cohort, were identified. An expert in occupational medicine reviewed the occupational history and allocated the patients to one of the following groups: probable exposure to crystalline silica, probable exposure to solvents, probable exposure to other toxins, or no suspected occupational exposure. Clinical characteristics were extracted from the Belgian Systemic Sclerosis Cohort database. Sufficient data were available for 96/103 patients. Most of these male patients (70/96, 72.9%) had a history of occupational exposure, 55 patients were likely exposed to crystalline silica, 11 patients to solvents, 2 patients to both silica and solvents, and 2 patients to asbestos. Only 26 patients had no suspected occupational exposure (27.1%). We noticed a significant difference in smoking status between exposed and non-exposed patients, with the highest percentage of ever smokers in the group with solvent exposure (p = 0.011). We found no significant differences in disease phenotype between exposed and non-exposed patients. However, we noted a trend to a higher prevalence of anti-Scl70 antibodies, cardiac dysfunction, and higher disease activity score in patients with occupational exposure. We observed a strikingly high prevalence of occupational exposure to both silica and solvents in male systemic sclerosis patients. Occupational exposure to silica or solvents is highly prevalent in male systemic sclerosis patients.


Assuntos
Doenças Profissionais/etiologia , Exposição Ocupacional/estatística & dados numéricos , Escleroderma Sistêmico/etiologia , Dióxido de Silício/toxicidade , Solventes/toxicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Prevalência , Estudos Prospectivos , Escleroderma Sistêmico/epidemiologia
19.
Clin Chem Lab Med ; 56(6): 909-918, 2018 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-29306915

RESUMO

BACKGROUND: Antinuclear antibodies (ANAs) are useful for the diagnosis of ANA-associated systemic rheumatic disease (AASRD). The objective of this study was the evaluation of an immunoassay that detects antibodies to a mixture of 17 antigens as an alternative to indirect immunofluorescence (IIF). METHODS: Nine thousand eight hundred and fifty-six consecutive patients tested for ANAs were tested by IIF and EliA connective tissue disease screen (Thermo-Fisher). Medical records were reviewed for 2475 patients, including all patients that tested positive/equivocal by either test and a selection of 500 patients that tested negative. RESULTS: Concordance between IIF and EliA was 83.1%. AASRD was found in 12.8% of IIF-positive patients, 30.2% of EliA-positive patients and 0.4%, 46.6%, 5.8% and 3.0% of patients that tested, respectively, double negative, double positive, single positive for EliA and single positive for IIF. The association with AASRD increased with increasing antibody level. IIF and EliA were positive in, respectively, 90.4% and 69.9% of systemic lupus erythematosus (n=83), 100% and 84.1% of systemic sclerosis (n=63), 86.7% and 93.3% of Sjögren's syndrome (n=45), 88.2% and 52.9% of polymyositis/dermatomyositis (n=17), and in all cases of mixed connective tissue disease (n=8). The specificity was projected to be 94%-96% for EliA and 86% for IIF. When all AASRDs were taken together, the areas under the curve of receiver operator curves were similar between IIF and EliA. CONCLUSIONS: The positive predictive value for AASRD was higher for EliA than for IIF, but, depending on the disease, EliA might fail to detect antibodies that are detected by IIF. Combining immunoassay with IIF adds value.

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