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1.
Artigo em Inglês | MEDLINE | ID: mdl-31642908

RESUMO

OBJECTIVES: Patients with SLE are often exposed to prolonged immunosuppression since few data on flare recurrence in remitted patients who discontinued immunosuppressants are available. We aimed to assess the rate and predictors of flare after immunosuppressant withdrawal in SLE patients in remission. METHODS: SLE patients diagnosed between 1990 and 2018 (according to the ACR criteria), ever treated with immunosuppressants and currently in follow-up were considered. Immunosuppressant discontinuation was defined as complete withdrawal of any immunosuppressive drug. Reasons for discontinuation were remission, defined as clinical SLEDAI-2K = 0 on a stable immunosuppressive and/or antimalarial therapy and/or on prednisone ⩽5 mg/day, or poor adherence/intolerance. Flares were defined according to the SLEDAI Flare Index. Predictors of a subsequent flare were analysed by multivariate logistic regression. RESULTS: There were 319 eligible patients out of 456 (69.9%). Of the 319 patients, 139 (43.5%) discontinued immunosuppressants, 105 (75.5%) due to remission, 34 (24.5%) due to poor adherence/intolerance. The mean (s.d.) follow-up time after immunosuppressant withdrawal was 91 (71) months (range 6-372). Among the patients who discontinued immunosuppressants, 26/105 remitted (24.7%) and 23/34 unremitted patients (67.6%) experienced a flare (P < 0.001) after a median (range) follow-up of 57 (6-264) and 8 months (1-72), respectively (P = 0.009). In patients who discontinued immunosuppressants due to remission, maintenance therapy with antimalarials (OR 0.243, 95% CI 0.070, 0.842) and the duration of remission at immunosuppressant discontinuation (OR 0.870, 0.824-0.996) were independent protective factors against disease flare. CONCLUSION: SLE flares are not uncommon after immunosuppressant discontinuation, even in remitted patients; however, antimalarial therapy and durable remission can significantly reduce the risk of flare.

2.
Curr Opin Rheumatol ; 31(6): 603-610, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31503025

RESUMO

PURPOSE OF REVIEW: Lung involvement is a distinctive feature of antisynthetase syndrome (ASS) and it is considered a basic disease-classifying criterion. In this review, we go over clinical features, radiological patterns, prognostic factors, pathogenesis and treatment of lung involvement in ASS patients, focusing on the clinical differences linked to the different antibody specificities known so far. RECENT FINDINGS: The lung is the most common extramuscular organ involved in ASS and has the greatest impact on patient prognosis. The pulmonary disease-defining manifestation in ASS is interstitial lung disease (ILD), yet a proportion of patients also develop pulmonary arterial hypertension and, less frequently, obstructive bronchiolitis or acute respiratory failure according to drivers not yet fully understood but likely associated with the underlying autoantibody pattern. Clinical presentation of pulmonary involvement can range from milder forms to a rapidly progressive disease which may lead to chronic lung damage if misdiagnosed and not properly treated. SUMMARY: The knowledge of risk factors associated with progressive or refractory lung damage is important to identify and properly treat patients with the poorest prognosis. For those with a disease not responsive to conventional therapy the efficacy of other therapeutic option is under evaluation.

3.
Urologia ; : 391560319876821, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31545701

RESUMO

Prostate cancer is the most frequent non-cutaneous malignancy in men in the United States. In the last few years, many recommendations have been made available from the 2014 International Society of Urologic Pathology consensus conference, 2016 World Health Organization blue book and 2018 8th edition of American Joint Committee on Cancer Staging System. Here, we focus on four topics which are considered relevant on the basis of their common appearance in routine practice, clinical importance and 'need to improve communication between pathology reports and clinicians': prostate cancer classification, prostate cancer grading, prostate cancer staging, and current definition of clinically significant prostate cancer. Tissue biomarkers that can predict significant disease and/or upgrading and tissue-based genomics for the purpose of diagnosis and prognosis are mentioned briefly.

4.
Ann Rheum Dis ; 78(9): 1151-1159, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31383717

RESUMO

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.

5.
Arthritis Rheumatol ; 71(9): 1400-1412, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31385462

RESUMO

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.

7.
Clin Exp Rheumatol ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31376254

RESUMO

OBJECTIVES: To present the results of a Delphi consensus survey among Italian paediatric and adult rheumatologists on transitional care (TC) of young people (YP) with juvenile idiopathic arthritis (JIA). METHODS: A taskforce of 27 paediatric and adult rheumatologists evaluated the applicability of the 2016 EULAR/PReS recommendations for TC to the Italian rheumatology practice and healthcare system and formulated additional country-specific statements aimed to increase their suitability. After a two-round discussion, applicability of EULAR/PReS recommendations and agreement with newly-proposed statements were voted on a 0-10 scale (where 0 = no applicability/agreement and 10 = total applicability/agreement). A mean level of agreement ≥8 was deemed acceptable. RESULTS: The consensus threshold was reached for only 4 of the 12 EULAR/PReS recommendations and for 25 of the 27 country-specific statements. Poor agreement with EULAR/PReS recommendations was mostly explained by paucity of centres in Italy that possess both paediatric and adult rheumatologists, disagreement about optimal time of transition start and de nition of transition coordinator, diversity between paediatric and adult clinimetric assessments, and lack of administrative and financial support. CONCLUSIONS: This consensus initiative represents an important step forward toward the establishment of a nationwide TC network for YP with JIA in Italy. The main goals established for the future are the identification of adult rheumatology centres that are willing to participate in the TC process, the education of adult rheumatology teams on childhood-onset rheumatic diseases and transition issues, and the increased awareness of public healthcare authorities and other stakeholders about the importance of good-quality TC.

8.
Clin Exp Rheumatol ; 37(5): 862-871, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31376250

RESUMO

The latest revision of the European League Against Rheumatism (EULAR) recommendations for rheumatoid arthritis (RA) treatment maintains the indication for the combined therapy of biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), namely Jak-inhibitors as tofacitinib and baricitinib, with conventional synthetic DMARDs (csDMARDs). Moreover, the use of bDMARDs and tsDMARDs should be restricted to patients who failed to achieve an adequate response to one or more csDMARDs, in accordance with the current evidence showing the superiority of combination therapy over monotherapy. In patients who cannot use csDMARDs as comedication, IL-6 inhibitors and tsDMARDs should be preferred to other bDMARDs because they are apparently more effective as monotherapy. Registry and real-world data demonstrate that monotherapy is far more commonly used than expected based on treatment recommendations, currently being about 30% of patients with RA on bDMARD monotherapy. We review here the literature on most commonly used DMARDs in monotherapy for RA. Our review points at an increasing evidence of the potential of some bDMARDs and tsDMARDs in monotherapy, which may become a considerable and realistic option in RA patients.


Assuntos
Antirreumáticos , Artrite Reumatoide , Inibidores de Janus Quinases , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Quimioterapia Combinada , Humanos , Inibidores de Janus Quinases/uso terapêutico , Conduta do Tratamento Medicamentoso , Sistema de Registros , Resultado do Tratamento
10.
Pediatr Radiol ; 49(9): 1201-1208, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203404

RESUMO

BACKGROUND: Concern regarding gadolinium deposition in the brain after repeated administration of intravenous gadolinium-based contrast agents has prompted evaluation of imaging alternatives. OBJECTIVE: The study purpose was to determine if magnetic resonance imaging (MRI) using conventional sequences with diffusion-weighted imaging (DWI) instead of gadolinium-based contrast-enhanced MRI is valid for local staging and guiding biopsies in osseous sarcomas. MATERIALS AND METHODS: Initial pretreatment MRI with DWI and gadolinium-based contrast-enhanced images in patients ≤ 18 years with histopathologically proven osseous sarcomas were included. Two radiologists blinded to collated demographic and clinical data, independently reviewed conventional/DWI and conventional/gadolinium-based contrast-enhanced MRI then conventional sequences alone, recording tumor size, skip lesions, necrosis, neurovascular invasion, enlarged lymph nodes and diffusion restriction. Discrepancies were resolved by a third reader. A single reader measured apparent diffusion coefficient (ADC) values in non-necrotic tumors, then correlated minimum ADC values -- with and without normalization to skeletal muscle -- with relative enhancement. RESULTS: Twenty-one patients (mean age: 11.3±4.2 years, 15 [71%] females) had 14 osteosarcomas and 7 Ewing sarcomas, 50% centered in the femur. Conventional/DWI versus conventional/gadolinium-based contrast-enhanced MRI showed agreement for tumor size estimation with significant associations for necrosis (P=0.021), neurovascular involvement (P<0.001) and enlarged lymph nodes (P=0.005). Diagnostic accuracy of conventional/DWI is comparable to conventional/gadolinium-based contrast-enhanced MRI and superior to conventional sequences alone. Comparison between minimum ADC values and relative enhancement showed no correlation (P>0.05). CONCLUSION: Significant associations of key imaging features in the initial assessment of osseous sarcomas support DWI as an alternative to gadolinium-based contrast-enhanced MRI. The lack of association between ADC values and relative enhancement suggests that they measure independent constructs, DWI dependent upon tumor cellularity and perfusion.

11.
Clin Rheumatol ; 38(10): 2843-2850, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254236

RESUMO

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD), potentially evolving into liver fibrosis (LF), is frequent in psoriasis (PsO), but data in psoriatic arthritis (PsA) are lacking. Our study aimed to investigate the prevalence of NALFD and LF in PsA/PsO and the contribution of arthritis in their onset. METHOD: PsA and PsO patients were consecutively enrolled. Exclusion criteria were liver diseases causing fibrosis (except NAFLD), alcohol ≥ 20 g/day, daily use of non-steroidal anti-inflammatory drugs and current/previous methotrexate use. Clinical history, biochemical and clinimetrical data and insulin-resistance index HOMA (homeostatic model assessment) were assessed. Patients underwent a liver ultrasound to identify steatosis (therefore NAFLD) and transient elastography, to evaluate LF (stiffness≥ 7 kPa = fibrosis). Statistical analysis included basic statistics, logistic and linear regression analyses (to assess the contribution of arthritis to NAFLD and LF grading, respectively) and Spearman's correlations; p ≤ 0.05 was considered significant. RESULTS: Seventy-six patients were enrolled (PsA/PsO 43/33). MetS and LF prevalence were similar between PsA and PsO (35% vs 33%, p = 0.88; 31% vs 28%, p = 0.77, respectively). NAFLD was more frequent in PsO (65% vs 35%, p = 0.044). In multivariable models with NAFLD and LF grading as outcomes, arthritis was not a significant predictor, while HOMA was independently associated with both (OR 1.34; 95%CI 1.06, 1.69; beta 0.88; 95%CI 0.54, 1.21, respectively). Female sex was independently associated with LF grading (beta 1.81; 95%CI 0.05, 3.57). CONCLUSIONS: NAFLD was more frequent in PsO, but MetS and LF prevalence were similar in PsA and PsO. Insulin resistance is the main determinant of NAFLD and LF, while additional contribution of arthritis seems small. Key Points • The prevalence of metabolic comorbidities, including liver fibrosis, is overall quite similar between psoriatic arthritis and psoriasis. • NAFLD is more frequently found in psoriasis than psoriatic arthritis. • The contribution of arthritis in the onset of metabolic comorbidities seems small.

12.
Ann Rheum Dis ; 78(7): 996-1002, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31138531

RESUMO

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies. METHODS: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups. RESULTS: We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10-5. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28×10-53 and HLA-DRB1*03:01, p=3.25×10-9), anti-PM/Scl (HLA-DQB1*02:01, p=1.47×10-26) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40×10-11). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92×10-13) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09×10-6). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47×10-64) and position 9 of HLA-B (p=7.03×10-11). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies. CONCLUSIONS: These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.

13.
Ultrasound Med Biol ; 45(8): 1918-1923, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31104865

RESUMO

The purpose of this study was to quantify the stiffness of hypertrophic scars using acoustic radiation force impulse ultrasound elastography. Sixteen pediatric patients with hypertrophic scars resulting from burn injuries participated in this study (mean age: 5.13, standard deviation: 3.20). Values for the elastic modulus (E) of scar and control sites were obtained. Scarred areas were found to be almost four times stiffer than control sites (scar Emean = 39.29 kPa compared with control Emean = 10.19 kPa) (p = 0.0004). Correlations between scar stiffness and clinician-reported subjective scar scale scores were not observed (rs = 0.30, p = 0.27 and rs = 0.25, p = 0.35 respectively). We found that acoustic radiation force impulse imaging can discriminate between hypertrophic scars and normal skin and should be considered a potentially valuable tool in the armamentarium of objective scar measures. Future research should focus on evaluating the technology's ability to detect scar change over time in order to determine responsiveness to treatment.

14.
Clin Exp Rheumatol ; 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30943146

RESUMO

OBJECTIVES: The 5-item Compliance Questionnaire for Rheumatology (CQR5) proved reliability and validity in respect of identification of patients likely to be high adherers (HAs) to anti-rheumatic treatment, or low adherers (LAs), i.e. taking<80% of their medications correctly. The objective of the study was to validate an Italian version of CQR5 (I-CQR5) in rheumatoid arthritis (RA) patients and to investigate factors associated with high adherence. METHODS: RA patients, undergoing treatment with ≥1 self-administered conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) or biological DMARD (bDMARD), were enrolled. The cross-cultural adaptation and validation of I-CQR5 followed standardised guidelines. I-CQR5 was completed by patients on one occasion. Data were subjected to factor analysis and Partial Credit model Parametrisation (PCM) to assess construct validity of I-CQR5. Analysis of factors associated with high adherence included demographic, social, clinical and treatment information. Factors achieving a p<0.10 in univariate analysis were included in multivariable analysis. RESULTS: Among 604 RA patients, 274 patients were included in the validation and 328 in the analysis of factors associated with adherence. Factor analysis and PCM confirmed the construct validity and consistency of I-CQR5. HAs were found to be 109 (35.2%) of the patients. bDMARD treatment and employment were found to be independently associated with high adherence: OR 2.88 (1.36-6.1), p=0.006 and OR 2.36 (1.21-4.62), p=0.012, respectively. CONCLUSIONS: Only one-third of RA patients were HAs according to I-CQR5. bDMARDs and employment status increased by almost 3-fold the likelihood of being highly adherent to the anti-rheumatic treatment.

16.
Expert Rev Clin Immunol ; 15(6): 617-627, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30933534

RESUMO

INTRODUCTION: Systemic Lupus Erythematosus (SLE) mostly affects women during their childbearing years. Fertility is preserved in SLE patients, but pregnancy is often characterized by a high number of maternal and fetal complications. Adverse pregnancy outcomes (APO) have been widely studied over the last decades and several investigators have focused on the potential clinical and serological predictors of maternal and fetal complications. Areas covered: In this review, we analyzed maternal and fetal complications in SLE patients and predictors of APO. Active disease in the 6 months before conception, lupus nephritis, anti-phospholipid (aPL), anti-SSA/Ro and/or anti-SSB/La antibodies have been identified as the most consistent predictors of maternal and fetal complications to date. However, molecular mechanisms and underlying immunological pathways involved in APO still remain elusive. Expert opinion: Difficulties in assessing prevalence and predictors of APO in SLE patients are due to lack of uniformity in the definitions and methods used in the different studies. In addition, some maternal and fetal complications are difficult to diagnose and to differentiate from each other. Preconception counseling is paramount to prevent APO, and it should consider four main factors: disease activity/lupus nephritis, safety of drugs, aPL, anti-SSA/Ro, and/or anti-SSB/La antibodies.

17.
AJR Am J Roentgenol ; : 1-14, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30860884

RESUMO

OBJECTIVE: Accurate and reproducible MRI assessment of the sacroiliac joint (SIJ) is challenging. Numerous scoring systems have been proposed to facilitate consistent SIJ assessment. The purpose of this article is to evaluate the diagnostic accuracy and reliability of existing MRI-based SIJ scoring systems for the evaluation of spondyloarthropathy. CONCLUSION: Among existing methods, there is fair (grade B) evidence to recommend the Spondyloarthropathy Research Consortium of Canada scoring systems as tools for MRI evaluation of the SIJ. However, limited data on criterion validity limit assessment of scoring system accuracy.

18.
Ann Rheum Dis ; 78(6): 736-745, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30926722

RESUMO

Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.

19.
Jpn J Radiol ; 37(5): 371-379, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30875012

RESUMO

Mixed connective tissue disease (MCTD) is a rare disease in children and adolescents which overlaps features of juvenile idiopathic arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, and systemic sclerosis. We have provided an image-based approach for evaluation of MCTD in children and adolescents, outlying the most frequent imaging findings. This approach would aid imagers and clinicians to consider the diagnosis of this rare entity and be able to make an accurate list of differential diagnosis for complex rheumatologic diseases such as MCTD, thus facilitating the ultimate goal of early diagnosis and optimal management of affected children.


Assuntos
Diagnóstico por Imagem/métodos , Doença Mista do Tecido Conjuntivo/diagnóstico por imagem , Adolescente , Criança , Diagnóstico Diferencial , Humanos
20.
Front Immunol ; 10: 29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30740098

RESUMO

Background: Pentraxin3 (PTX3) is overexpressed in kidneys of patients developing lupus nephritis (LN). Active LN is associated with reduced anti-PTX3 antibodies. However, abnormalities of B cell differentiation against PTX3 have not been characterized in systemic lupus erythematosus (SLE). Objective: Characterization of PTX3-specific (PTX3+) B cells in peripheral blood of SLE patients with or without LN and healthy donors (HD). Patients and Methods: SLE patients without LN, biopsy-proven LN and matched HD were analyzed. Active LN was defined as proteinuria>0.5 g/day or CrCl<60 ml/min/1.73 m2 with active urinary sediment. Peripheral B cells were analyzed for direct PTX3 binding by flow cytometry using PTX3 labeled with cyanine 5 (Cy5) and phycoerythrin (PE). Results: Initially, a flow cytometry based assay to identify PTX3+ B cells was developed by demonstrating simultaneous binding of PTX3-Cy5 and PTX3-PE. Specificity of B cells was validated by blocking experiments using unlabeled PTX3. We could identify circulating PTX3+ B-cells in HD and patients. Notably, LN patients showed a significantly diminished number of PTX3+ B cells (SLE vs. LN p = 0.033; HD vs. LN p = 0.008). This decrease was identified in naïve and memory B cell compartments (naïve: SLE vs. LN p = 0.028; HD vs. LN p = 0.0001; memory: SLE vs. LN p = 0.038, HD vs. LN p = 0.011). Conclusions: Decreased PTX3+ B cells in LN within the naïve and memory compartment suggest their negative selection at early stages of B cell development potentially related to a decreased regulatory function. PTX3+ B cells could candidate for autoantigen-defined regulatory B cells as a striking abnormality of LN patients.

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