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The 1st GRAPPA International Meeting on Psoriasis and Psoriatic Arthritis - 1° Encontro Internacional do GRAPPA Sobre Psoríase e Artrite Psoriásica was held on August 18-19, 2023, in São Paulo, Brazil, and marked a turning point in the management of psoriasis (PsO) and psoriatic arthritis (PsA) in our country. This was an international collaboration, between Brazilian rheumatologists and dermatologists and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), aiming to promote medical knowledge and particularly the optimal care and management of Brazilian patients with psoriatic disease (PsD).
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We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 µg/300 µL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 µL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10+ and FoxP3+ cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis.
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Artritis Experimental , Colágeno Tipo V , Ratas Endogámicas Lew , Membrana Sinovial , Animales , Masculino , Administración Oral , Ratas , Artritis Experimental/inmunología , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Membrana Sinovial/inmunología , Membrana Sinovial/patología , Colágeno Tipo V/inmunología , Colágeno Tipo V/administración & dosificación , Adyuvante de Freund/administración & dosificación , Inmunoterapia/métodos , Interleucina-10 , Factores de Transcripción Forkhead/metabolismo , Albúmina Sérica BovinaRESUMEN
Multidisciplinary care is essential for the management of patients with psoriatic disease (PsD), considering the great range of cutaneous and musculoskeletal symptoms and the potential for associated comorbidities and extraarticular manifestations. Consequently, combined rheumatology/dermatology clinics represent a gold standard model of care for patients with PsD. Many challenges are associated with the establishment of these clinics in routine clinical practice. In this report, we describe the thoughts and debates within a collaborative care breakout session during the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting. The breakout discussion focused around 3 main topics: (1) challenges of dermatologist-rheumatologist collaboration; (2) innovative approaches to encourage collaboration; and (3) how to identify patients with psoriasis at high risk of developing PsA.
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Artritis Psoriásica , Dermatólogos , Psoriasis , Reumatólogos , Reumatología , Humanos , Psoriasis/terapia , Artritis Psoriásica/terapia , Artritis Psoriásica/diagnóstico , Dermatología/métodos , Grupo de Atención al Paciente/organización & administraciónRESUMEN
Background: Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement. Methods: Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels. Results: Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls. Conclusion: This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.
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Dermatomiositis , Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Anticuerpos Antinucleares , Apoptosis , Proteína X Asociada a bcl-2 , Caspasa 3 , Dermatomiositis/complicaciones , Células Asesinas Naturales , Receptores Tipo I de Factores de Necrosis TumoralRESUMEN
OBJECTIVES: To analyze longstanding polyarticular juvenile idiopathic arthritis (pJIA) for possible associations between localized bone damage (erosions), and systemic bone loss. Besides, to compare the systemic bone mass of pJIA with healthy controls. METHODS: Thirty-four pJIA women and 99 healthy controls (HC) were included. Radius and tibia of all subjects were scanned by HR-pQCT. Volumetric bone mineral density (vBMD), bone microarchitecture, and -finite element parameters were analyzed. Patients underwent HR-pQCT of 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the dominant hand, for bone erosions quantification. RESULTS: The mean age of patients was 31.5 ± 7.4yrs with a mean disease duration of 21.7 ± 9.2yrs. Bone erosions were detectable in 79% of patients. The number of bone erosions was positively correlated with cortical porosity (Ct.Po) at tibia (r = 0.575, p = 0.001), and radius (r = 0.423, p = 0.018); and negatively correlated with cortical vBMD at tibia (r=-0.420, p = 0.015). In a logistic regression analysis, adjusted for anti-CCP, the presence of bone erosions was independently associated with Ct.Po at radius (p = 0.018) and cortical vBMD at tibia (p = 0.020). Moreover, cortical and trabecular vBMD, trabecular number, and µ-finite element parameters were decreased in patients compared to HC (p < 0.05). CONCLUSION: Bone erosions in longstanding pJIA women were associated with decreased cortical bone parameters, and these patients showed systemic bone impairment at peripheral sites compared with healthy controls.
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Artritis Juvenil , Osteoporosis , Humanos , Femenino , Adulto Joven , Adulto , Artritis Juvenil/complicaciones , Artritis Juvenil/diagnóstico por imagen , Densidad Ósea , Radio (Anatomía) , Tomografía Computarizada por Rayos X , Tibia/diagnóstico por imagen , Absorciometría de FotónRESUMEN
BACKGROUND: Despite the criteria already established for the classification of knee osteoarthritis (OA), a radiographic and/or clinical knee OA diagnosis usually occurs in cases of fully manifest or more advanced disease, which can make health promotion, prevention, and functional rehabilitation in more advanced stages of the disease less effective. In addition, radiographic knee OA can generate more financial costs for health services. Therefore, developing and validating screening instruments to assess the probability of development and progression of knee OA would be of great value for both clinical practice and science. OBJECTIVE: To cross-culturally adapt and investigate the measurement properties of the Knee OA Pre-screening Questionnaire Brazilian version. METHODS: A total of 250 individuals of both sexes aged between 35 and 92 years [(mean (standard deviation): 63 (11) years old; 74.1 (15.1) kg; 1.59 (0.09) m; 29.38 (5.44) kg/m2] participated in this study. The cross-cultural adaptation and analyses of the measurement properties of the KOPS Brazilian version included: (1) assessment of conceptual and item equivalence; (2) assessment of semantic equivalence; (3) assessment of operational equivalence; and (4) assessment of measurement equivalence, reliability, and validity. RESULTS: Cronbach's alpha for the internal consistency among the six components of the KOPS Brazilian version was 0.71. The test-retest 72 h apart for each component resulted in a coefficient correlation intraclass ranging from 0.74 to 1.00. The probability of an individual randomly chosen from the population having KL ≥ 1 and KOPS Brazilian version ≥ 21 points was 0.74 (area under the curve of the Receiver Operating Characteristic - AUC of ROC); furthermore, the AUC for KL ≥ 2 and the KOPS Brazilian version ≥ 23 points was 0.77. CONCLUSION: The KOPS Brazilian version is a reliable and valid instrument for early screening of knee OA in individuals aged 35 years and over in the Brazilian context.
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Osteoartritis de la Rodilla , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Niño , Brasil , Osteoartritis de la Rodilla/diagnóstico por imagen , Reproducibilidad de los Resultados , Comparación Transcultural , Encuestas y CuestionariosRESUMEN
Cutaneous fibrosis is one of the main features of systemic sclerosis (SSc). Recent findings correlated abnormal collagen V (Col V) deposition in dermis with skin thickening and disease activity in SSc. Considering that Col V is an important regulator of collagen fibrillogenesis, understanding the role of Col V in the first two years of the skin fibrosis in SSc (early SSc) can help to determine new targets for future treatments. In this study, we analyzed the morphological, ultrastructural and molecular features of α1(V) and α2(V) chains and the expression of their coding genes COL5A1 and COL5A2 in collagen fibrillogenesis in early-SSc. Skin biopsies were obtained from seven consecutive treatment-naïve patients with SSc-related fibrosis and four healthy controls. Our data showed increased α1(V) and α2(V) chain expression in the reticular dermis of early-SSc patients; however, immunofluorescence and ultrastructural immunogold staining determined a significant decreased expression of the α1(V) chain along the dermoepidermal junction in the papillary dermis from early-SSc-patients in relation to the control (12.77 ± 1.34 vs. 66.84 ± 3.36; p < 0.0001). The immunoblot confirmed the decreased expression of the α1(V) chain by the cutaneous fibroblasts of early-SSc, despite the increased COL5A1 and COL5A2 gene expression. In contrast, the α2(V) chain was overexpressed in the small vessels (63.18 ± 3.56 vs. 12.16 ± 0.81; p < 0.0001) and capillaries (60.88 ± 5.82 vs. 15.11 ± 3.80; p < 0.0001) in the reticular dermis of early-SSc patients. Furthermore, COLVA2 siRNA in SSc cutaneous fibroblasts resulted in a decreased α1(V) chain expression. These results highlight an intense decrease in the α1(V) chain along the dermoepidermal junction, suggesting an altered molecular histoarchitecture in the SSc papillary dermis, with a possible decrease in the expression of the α1(V)3 homotrimeric isoform, which could interfere with the thickening and cutaneous fibrosis related to SSc.
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Dermis , Esclerodermia Sistémica , Humanos , ARN Interferente Pequeño/metabolismo , Estructura Molecular , Dermis/metabolismo , Esclerodermia Sistémica/patología , Fibrosis , Colágeno/metabolismo , Piel/metabolismo , Fibroblastos/metabolismoRESUMEN
The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2nd dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6 months compared to 6 weeks after 2nd vaccine dose for decay evaluation. Secondary outcomes are presence of neutralizing antibodies, percent inhibition by neutralizing, geometric mean titers and cumulative incident cases at 6 months after 2nd dose. Anti-S1/S2 IgG positivity and titers reduce to 23.8% and 38% in patients (p < 0.001) during the six-month follow up and 20% and 51% in controls (p < 0.001), respectively. Neutralizing antibodies positivity and percent inhibition declines 41% and 54% in patients (p < 0.001) and 39.7% and 47% in controls (p < 0.001). Multivariate logistic regression analysis show males (OR = 0.56;95% CI0.40-0.79), prednisone (OR = 0.56; 95% CI0.41-0.76), anti-TNF (OR = 0.66;95% CI0.45-0.96), abatacept (OR = 0.29; 95% CI0.15-0.56) and rituximab (OR = 0.32;95% CI0.11-0.90) associate with a substantial reduction in IgG response at day 210 in patients. Although cellular immunity was not assessed, a decrease of COVID-19 cases (from 27.5 to 8.1/100 person-years; p < 0.001) is observed despite the concomitant emergence and spread of the Delta variant. Altogether we show a reduction in immunity 6-months of Sinovac-CoronaVac 2nd dose, particularly in males and those under immunosuppressives therapies, without a concomitant rise in COVID-19 cases. (CoronavRheum clinicaltrials.gov:NCT04754698).
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COVID-19 , Enfermedades Reumáticas , Vacunas Virales , Abatacept , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunoglobulina G , Incidencia , Masculino , Prednisona , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Rituximab/uso terapéutico , SARS-CoV-2 , Inhibidores del Factor de Necrosis Tumoral , Vacunas de Productos InactivadosRESUMEN
In this paper, we sought to determine the prevalence of arthritis mutilans in a single cohort of Brazilian psoriatic arthritis patients followed at a tertiary university reference center. Our study demonstrated a high prevalence of arthritis mutilans associated to comorbidities and biologic therapy. In addition, our data suggest that axial involvement may be an intriguing aspect of psoriatic arthritis mutilans and that rheumatologists should be aware of axial disease, even if the phenotype is marked by peripheral joint severity.
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Artritis Psoriásica , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Brasil/epidemiología , Humanos , Prevalencia , ReumatólogosRESUMEN
OBJECTIVE: The aim of this study was to examine the effect of clinical specialty setting on the management of psoriatic arthritis (PsA) as well as disease activity/burden in Brazil. METHODS: This study is a post hoc analysis of the Brazilian population in a cross-sectional, observational study conducted in 17 countries. Patients were 18 years or older with suspected or confirmed PsA attending routine visits at participating sites. Primary end points were time from symptom onset to PsA diagnosis, from diagnosis to first conventional systemic disease-modifying antirheumatic drug (DMARD) or first biologic DMARD, and from first conventional systemic DMARD to first biologic DMARD. Potential associations were assessed using the Student t test or the Mann-Whitney U nonparametric test. Normality was tested using the Shapiro-Wilk and Kolmogorov-Smirnov tests. For qualitative variables, the χ2 test was adopted. RESULTS: Patients (n = 130) visited dermatology (n = 75) or rheumatology (n = 55) sites. All primary end points were similar between the 2 settings; however, dermatology patients had significantly greater enthesitis counts (2.1 vs 0.6; p = 0.002), absenteeism at work (Work Productivity and Activity Impairment, 19.7% vs 5.2%; p = 0.03), and pain (Health Assessment Questionnaire-Disability Index pain scale, 1.39 vs 1.01; p = 0.032), as well as worse quality of life related to psoriasis (Dermatology Life Quality Index total score, 8.5 vs 5.0; p = 0.019) and mental health (12-item Short-Form Health Survey, version 2.0 subscale, 42.4 vs 47.4; p = 0.029). CONCLUSIONS: In Brazil, PsA disease burden and disease activity were influenced by clinical specialty. Irrespective of setting, patients experienced a delay in being diagnosed with PsA, reinforcing the need for collaborative management of PsA by rheumatologists and dermatologists for better outcomes in these patients.
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Antirreumáticos , Artritis Psoriásica , Antirreumáticos/uso terapéutico , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Brasil/epidemiología , Estudios Transversales , Humanos , Calidad de VidaRESUMEN
Abstract Background: Despite the criteria already established for the classification of knee osteoarthritis (OA), a radiographic and/or clinical knee OA diagnosis usually occurs in cases of fully manifest or more advanced disease, which can make health promotion, prevention, and functional rehabilitation in more advanced stages of the disease less effective. In addition, radiographic knee OA can generate more financial costs for health services. Therefore, developing and validating screening instruments to assess the probability of development and progression of knee OA would be of great value for both clinical practice and science. Objective: To cross-culturally adapt and investigate the measurement properties of the Knee OA Pre-screening Questionnaire Brazilian version. Methods: A total of 250 individuals of both sexes aged between 35 and 92 years [(mean (standard deviation): 63 (11) years old; 74.1 (15.1) kg; 1.59 (0.09) m; 29.38 (5.44) kg/m2] participated in this study. The cross-cultural adaptation and analyses of the measurement properties of the KOPS Brazilian version included: (1) assessment of conceptual and item equivalence; (2) assessment of semantic equivalence; (3) assessment of operational equivalence; and (4) assessment of measurement equivalence, reliability, and validity. Results: Cronbach's alpha for the internal consistency among the six components of the KOPS Brazilian version was 0.71. The test-retest 72 h apart for each component resulted in a coefficient correlation intraclass ranging from 0.74 to 1.00. The probability of an individual randomly chosen from the population having KL ≥ 1 and KOPS Brazilian version ≥ 21 points was 0.74 (area under the curve of the Receiver Operating Characteristic - AUC of ROC); furthermore, the AUC for KL ≥ 2 and the KOPS Brazilian version ≥ 23 points was 0.77. Conclusion: The KOPS Brazilian version is a reliable and valid instrument for early screening of knee OA in individuals aged 35 years and over in the Brazilian context.
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Abstract In this paper, we sought to determine the prevalence of arthritis mutilans in a single cohort of Brazilian psoriatic arthritis patients followed at a tertiary university reference center. Our study demonstrated a high prevalence of arthritis mutilans associated to comorbidities and biologic therapy. In addition, our data suggest that axial involvement may be an intriguing aspect of psoriatic arthritis mutilans and that rheumatologists should be aware of axial disease, even if the phenotype is marked by peripheral joint severity.
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Collagen is essential for cartilage adhesion and formation. In the present study, histology, immunofluorescence, morphometry, and qRT-PCR suggested that adipose-derived stem cells (ADSCs) stimulated by type V collagen (Col V) induce a significant increase of type II collagen (Col II) in the degenerative area of surgical-induced osteoarthritic rabbit articular cartilage (OA). In vitro, the effects of Col V on the proliferation and differentiation of ADSC were investigated. The expression of the cartilage-related genes Col2a1 and Acan was significantly upregulated and Pou5fl was downregulated post-ADSC/Col V treatment. Post-ADSC/Col V treatment, in vivo analyses revealed that rabbits showed typical signs of osteoarthritic articular cartilage regeneration by hematoxylin and eosin (H&E) and Safranin O/Fast Green staining. Immunohistochemical staining demonstrated that the volume of Col II fibers and the expression of Col II protein were significantly increased, and apoptosis Fas ligand positive significantly decreased post-ADSC/Col V treatment. In conclusion, the expression of Col II was higher in rabbits with surgical-induced osteoarthritic articular cartilage; hence, ADSC/Col V may be a promising therapeutic target for OA treatment.
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OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.
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Artritis Psoriásica , Tuberculosis Latente , Espondilitis Anquilosante , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Estudios de Seguimiento , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Estudios Retrospectivos , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/epidemiologíaRESUMEN
INTRODUCTION/OBJECTIVES: Tyro3, Axl, and Mer (TAM) receptors and ligands mediate apoptotic bodies engulfment which alteration has been related with juvenile systemic lupus erythematosus (JSLE) pathogenesis. Thus, the aim was to determine their soluble levels. METHODS: Serum sTyro3, sAxl, sMer, and Gas6 levels were measured using ELISA in 67 JSLE patients, 12 juvenile idiopathic arthritis (JIA) inflammatory and 20 healthy controls and related with SLEDAI-2K score, anti-dsDNA antibody, ESR, CRP, C3, C4 levels, and nephritis. RESULTS: JSLE patients with active disease (SLEDAI-2K> 4) had significantly increased sMer levels compared with healthy controls (median 8.4 vs. 6.0 ng/mL, p = 0.009) and inactive disease patients (5.2 ng/mL, p = 0.0003). sMer levels correlated with SLEDAI-2K (r = 0.44; p = 0.0004) and ESR (r = 0.24; p = 0.04), while sAxl correlated with SLEDAI-2K (r = 0.33; p = 0.008) and C4 levels (r = - 0.24; p = 0.04). JSLE patients taking glucocorticoid had increased sAxl and sMer levels. Moreover, sAxl correlated with sMer and sTyro3 levels. Patients with nephritis and those with focal or diffuse proliferative glomerulonephritis had these protein levels similar to healthy controls and patients without renal involvement. sTyro3 levels of JSLE patients taking glucocorticoid were decreased, and correlated with Gas6 and sAxl, while Gas6 levels correlated with age upon enrollment. JIA controls had protein levels similar to healthy controls and JSLE patients. CONCLUSIONS: This study reinforces that sMer is increased in active JSLE patients, yet sMer and sAxl correlates with disease activity parameters, and their alterations are disease-specific. However, further studies are needed to determine exact roles of sTyro3 and Gas6 in disease pathogenesis. Key Points ⢠sMer and sAxl serum levels are related with active disease in JSLE patients ⢠sMer correlated with SLEDAI-2K score in JSLE ⢠sTyro3, sAxl, sMer and Gas6 levels did not related with nephritis in JSLE patients ⢠sTyro3 and Gas6 exact roles in JSLE are not established and further studies are needed.
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Péptidos y Proteínas de Señalización Intercelular/sangre , Lupus Eritematoso Sistémico/sangre , Proteínas Proto-Oncogénicas/sangre , Proteínas Tirosina Quinasas Receptoras/sangre , Tirosina Quinasa c-Mer/sangre , Estudios de Casos y Controles , Humanos , Tirosina Quinasa del Receptor AxlRESUMEN
OBJECTIVE: To assess the longitudinal production of anti-adalimumab antibody (AAA) and baseline risk factors for this antibody development in juvenile idiopathic arthritis (JIA) patients initiating adalimumab (ADA). METHOD: Thirty consecutive JIA patients under ADA therapy were prospectively followed. JIA clinical/laboratorial/treatment data and sera for ADA and AAA assays (ELISA and bridging ELISA) were obtained at baseline (BL), 2 months (2M), 3 months (3M), 6 months (6M), 12 months (12M), and 24 months (24M). Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels). RESULTS: AAA was absent at BL, first detected at 2M after ADA initiation in 2/30 (7%) patients with a significant increase at 3M (10/29 (34%), p = 0.013) and no major change in 6M (11/30 (37%)) and 12M (9/26 (35%)). Of note, at 3M, AAA levels correlated negatively with ADA levels (r = - 0.781, p = 0.0001). Analysis of BL predictors revealed a significantly higher risk of developing AAA in patients with female gender (OR 21; 95% CI 1.08-406.57; p = 0.044), ESR > 30 mm/1st hour (OR 5.44; 95% CI 1.04-28.53; p = 0.045), and leflunomide use (OR 9.33; 95% CI 1.51-57.66; p = 0.016). In contrast, concomitant use of methotrexate was protective for AAA appearance (OR 0.08; 95% CI 0.01-0.53; p = 0.009). After 12M of ADA, 60% of AAA-positive patients required drug switch for drug failure compared with 15% in AAA-negative group (p = 0.03). CONCLUSIONS: This study provides novel evidence of AAA production kinetics demonstrating a timely significant increase starting at 3M and stable throughout 24M. We also identified female gender, increased ESR, and leflunomide use as relevant risk factors for AAA production at BL, whereas methotrexate was protective. Early systematic monitoring of AAA at 3M may, therefore, guide drug switching in these patients.Key Points⢠Anti-adalimumab antibodies (AAA) production kinetics demonstrated a timely significant increase starting at 3M in juvenile idiopathic arthritis (JIA) patients under adalimumab therapy⢠Female gender, increased ESR, and leflunomide use were identified as relevant risk factors for AAA production in JIA, whereas methotrexate was protective.
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Adalimumab/uso terapéutico , Anticuerpos/metabolismo , Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Sustitución de Medicamentos , Leflunamida/uso terapéutico , Metotrexato/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Uveítis/tratamiento farmacológico , Adalimumab/inmunología , Adolescente , Adulto , Formación de Anticuerpos , Sedimentación Sanguínea , Niño , Preescolar , Quimioterapia Combinada , Femenino , Humanos , Cinética , Masculino , Oportunidad Relativa , Factores Protectores , Factores de Riesgo , Factores Sexuales , Inhibidores del Factor de Necrosis Tumoral/inmunología , Adulto JovenRESUMEN
Patients with Systemic sclerosis (SSc) presents immune dysregulation, vasculopathy, and fibrosis of the skin and various internal organs. Pulmonary fibrosis leads to SSc-associated interstitial lung disease (ILD), which is the main cause of morbidity and mortality in SSc. Recently autoimmunity to type V collagen (Col V) has been characterized in idiopathic pulmonary fibrosis and show promise to be related to the development in SSc. Our aim was to evaluate autoimmunity to Col V α1(V) and α2(V) chains and to the antigenic peptides of these Col V chains in early-SSc sera employing lung tissue of SSc-ILD, as antigen source. We found that sera samples from patients with early-SSc were reactive to Col V (41.18%) and presented immunoreactivity for Col5A1(1.049) and Col5A1(1.439) peptides. The IgG isolated from early-SSc patients-anti-Col V positive sera (anti-ColV IgG) was adsorbed with α1(V) chain (anti-ColV IgG/ads-α1(V)) and α2(V) chain (anti-ColV IgG/ads-α2(V)) and biotinylated to evaluate the spectrum of reactivity in SSc-ILD patients lung biopsies by immunofluorescence. The SSc-ILD lung tissue samples immunostained with anti-ColV IgG showed increased green fluorescence in the vascular basement membrane, bronchiolar smooth muscle, and adventitial layer, contrasting with the tenue immunostaining in control lungs. Col V protein expression in these pulmonary compartments immunostained with early-SSc anti-ColV IgG was confirmed by immune colocalization assays with commercial anti-human Col V antibodies. In addition, SSc-ILD lung tissues immunostained with anti-ColV IgG/ads-α1(V) (sample in which Col V α1 chain-specific antibodies were removed) showed decreased green fluorescence compared to anti-ColV IgG and anti-ColV IgG/ads-α2(V). Our data show that autoimmunity to Col V in early-SSc was related to peptides of the α1(V) chain, suggesting that these antibodies could be biomarkers of SSc stages and potential target of immunotherapy with Col V immunogenic peptides.
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Autoanticuerpos/sangre , Autoinmunidad , Colágeno Tipo V/inmunología , Inmunoglobulina G/sangre , Enfermedades Pulmonares Intersticiales/inmunología , Pulmón/inmunología , Esclerodermia Sistémica/inmunología , Biomarcadores/sangre , Estudios de Casos y Controles , Diagnóstico Precoz , Humanos , Inmunohistoquímica , Pulmón/patología , Enfermedades Pulmonares Intersticiales/diagnóstico , Valor Predictivo de las Pruebas , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/diagnóstico , Pruebas SerológicasRESUMEN
Abstract Background: The aims of this article were to assess the prevalence of nephrolithiasis and the factors associated with nephrolithiasis in Brazilian patients with primary gout. Methods: One hundred twenty-three patients with primary gout were recruited from a tertiary referral hospital in São Paulo, Brazil. All patients underwent ultrasonography and had their clinical and laboratory characteristics assessed. Results: One hundred fifteen (93.5%) patients were male, with a mean age of 62.9 ± 9.4 years. Twenty-three (18.7%) patients had asymptomatic nephrolithiasis (detected only by ultrasonography), 7 (6.0%) had symptomatic nephrolithiasis (detected by ultrasonography and a positive clinical history), and 13 (10.0%) had a history of kidney stones, but ultrasonography at evaluation did not show nephrolithiasis. Therefore, 35.0% of the patients had nephrolithiasis (detected either by ultrasonography and/or a positive clinical history). Nephrolithiasis was associated with male gender (43 [100%] vs 72 [90%], p = 0.049), the use of potassium citrate (13 [30.2%] vs 0, p < 0.001) and the use of medications for diabetes (10 [23.3%] vs 8 [10%], p = 0.047) and dyslipidemia (15 [34.9%] vs 10 [12.5%], p = 0.003); benzbromarone had an inverse association with nephrolithiasis (21 [48.8%] vs 55 [68.8%], p = 0.030). In patients with and without nephrolithiasis, no differences were found in the laboratory and ultrasonography characteristics, including serum uric acid levels, urinary uric acid excretion and urine pH. Conclusions: The prevalence of nephrolithiasis in primary gout was 35.0%, and 18.7% of the patients were asymptomatic. Nephrolithiasis was associated with male gender, diabetes and dyslipidemia. A positive history of nephrolithiasis probably biased the prescription of potassium citrate and benzbromarone.(AU)
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Humanos , Síndrome Metabólico , Nefrolitiasis/epidemiología , Gota/fisiopatología , Brasil/epidemiología , Benzbromarona/efectos adversos , Prevalencia , Citrato de Potasio/efectos adversos , Urolitiasis/etiologíaRESUMEN
OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.
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Humanos , Espondilitis Anquilosante/tratamiento farmacológico , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Espondilitis Anquilosante/epidemiología , Estudios Retrospectivos , Estudios de Seguimiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoRESUMEN
BACKGROUND: Adaptive immune cells, including CD4+CD69+ and CD4+CD25+FoxP3+ regulatory T (Treg) cells, are important for maintaining immunological tolerance. In human systemic lupus erythematosus (SLE), CD4+CD25+FoxP3+ Treg cells are reduced, whereas CD69 expression is increased, resulting in a homeostatic immune imbalance that may intensify autoreactive T cell activity. To analyze the mechanisms implicated in autotolerance failure, we evaluated CD4+CD69+ and CD4+CD25+FoxP3+ T cells and interleukin profiles in a pristane-induced SLE experimental model. METHODS: For lupus induction, 26 female Balb/c mice received a single intraperitoneal 0.5 ml dose of pristane, and 16 mice received the same dose of saline. Blood and spleen samples were collected from euthanized mice 90 and 120 days after pristane or saline inoculation. Mononuclear cells from peripheral blood (PBMC), peritoneal lavage (PL) and splenocytes were obtained by erythrocyte lysis and cryopreserved for further evaluation by flow cytometry using the GuavaEasyCyte TM HT. After thawing, cells were washed and stained with monoclonal antibodies against CD3, CD4, CD8, CD25, CD28, CD69, FoxP3, CD14 and Ly6C (BD Pharmingen TM). Interleukins were quantified using Multiplex® MAP. The Mann-Whitney test and the Pearson coefficient were used for statistical analysis, and p < 0.05 considered significant. RESULTS: Compared with the controls, SLE-induced animals presented increased numbers of CD4+CD69+ T cells in the blood on T90 and T120 (p = 0.022 and p = 0.008) and in the spleen on T120 (p = 0.049), but there were decreased numbers in the PL (p = 0.049) on T120. The percentage of Treg was lower in blood (p < 0.005 and p < 0.012) on T90 and T120, in spleen (p = 0.043) on T120 and in PL (p = 0.001) on T90. Increased numbers of CD4 + CD69+ T cells in the PL were positively associated with high IL-2 (p = 0.486) and IFN-γ (p = 0.017) levels, whereas reduced Treg cells in the blood were negatively correlated with TNFα levels (p = 0.043) and positively correlated with TGFß1 (p = 0.038). CONCLUSION: Increased numbers of CD4+CD69+ T cells and reduced numbers of CD4+CD25+FoxP3+ Treg cells with an altered interleukin profile suggests loss of autotolerance in pristane-induced lupus mice, which is similar to human lupus. Therefore, this model is useful in evaluating mechanisms of cellular activation, peripheral tolerance and homeostatic immune imbalance involved in human SLE.