Rheumatoid arthritis (RA) is associated with localized bone loss in the hands, as well as generalized osteoporosis. Joint erosions are the hallmark of RA. They are caused by an increased bone resorption and the RANKL/OPG system is the main regulator of osteoclast recruitment. In RA there is also no increased bone formation to prevent or heal these erosions. The Wnt pathway has a main role in the control of bone formation through regulation of osteoblast activity. Sclerostin and Dkk-1 are important regulators of this pathway.
Objectives
To determine the degree of association of disease activity with bone markers and bone mineral density (BMD) at different anatomical sites in patients with established RA, analyzing the differences according to therapy regimens (conventional DMARDs, exclusively, versus biologics, with or without conventional DMARDs).
Methods
Clinical caracteristics and blood samples were collected in a monitoring visit. Portuguese version of the Standford Health Assessment Questionnaire (HAQ), Disease Activity Score four variables (DAS28(4v)), 68 tender and 66 swollen joint counts were obtained. BMD was evaluated by DXA at the lumbar spine, total hip, femoral neck, Wards triangle, hands and second proximal phalanges. We measured ESR and CRP, serum β-C-telopeptide of collagen1 cross-links (β-CTX1), osteocalcin, Dkk-1 (ELISA, Biomedica), sclerostin (ELISA, TECOmedical), RANKL (ELISA, Cusabio), osteoprotogerin (ELISA, Biomedica) and serum serotonin (ELISA, Labor Diagnostika Nord). PASW Statistics 18 was used for statistical analysis.
Results
We evaluated 110 RA patients, 88 (80%) women, 56 (%) under biologics, age 54±11 years, 14±10 years of disease duration, mean DAS28(4v) of 4.25±1.31. In a multivariate modelling (after adjusting for age, BMI, disease duration, average daily dose of prednisone, years of corticosteroid use and years of anti-repsortive therapy) and in RA patients exclusively under conventional DMARDs, moderate disease activity, according DAS28(4v), was associated with higher sclerostin levels (p<0.05). There was a trend for higher RANKL levels among severely active patients. DAS28(4v) was negatively associated with femoral neck (p<0.05), hands (p<0.001) and second proximal phalanges (p<0.005) BMD. Using the same model and adjusting also for years of biologic therapy, in the group under biologic agents, sclerostin levels were positively associated with disease activity (p<0.05). Higher DAS28(4v) values were associated with lower total hip, femoral neck, hands and second proximal phalanges BMD (p<0.001).
Conclusions
In our RA population a strong negative association between disease activity and both hand and femoral BMD measurements was found. The link between high disease activity and increased sclerostin levels could represent a cause for decreased bone formation in active RA.
To analyze the clinical and epidemiologic characteristics of juvenile-onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult-onset (≥ 16 years) SpA patients. Prospective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE – Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset < 16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group). Among the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p < 0.001), lower limb arthritis (p = 0.001), enthesitis (p = 0.008), anterior uveitis (p = 0.041) and positive HLA-B27 (p = 0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index – BASDAI; p = 0.007) and functionality (Bath Ankylosing Spondylitis Functional Index – BASFI; p = 0.036). Cutaneous psoriasis (p < 0.001), inflammatory bowel disease (p = 0.023), dactylitis (p = 0.024) and nail involvement (p = 0.004) were more frequent in patients with adult-onset SpA. Patients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA-B27 and lower disease scores. Analisar as características clínicas e epidemiológicas da espondiloartrite (EspA) de início juvenil (< 16 anos) e compará-las com um grupo de pacientes com EspA de início na vida adulta (≥ 16 anos). Coorte prospectiva, observacional e multicêntrica com 1.424 pacientes com diagnóstico de EspA de acordo com o European Spondyloarthropathy Study Group (ESSG) submetidos a um protocolo comum de investigação e recrutados em 29 centros de referência participantes do Registro Brasileiro de Espondiloartrites (RBE). Os pacientes foram divididos em dois grupos: idade no início < 16 anos (grupo EspAiJ) e idade no início ≥ 16 anos. Entre os 1.424 pacientes, 235 manifestaram o início da doença antes dos 16 anos (16,5%). As variáveis clínicas e epidemiológicas associadas com a EspAiJ foram: gênero masculino (p < 0,001), artrite em membro inferior (p = 0,001), entesite (p = 0,008), uveíte anterior (p = 0,041) e HLA-B27 positivo (p = 0,017), em associação com escores mais baixos de atividade da doença (Bath Ankylosing Spondylitis Disease Activity Index – BASDAI; p = 0,007) e de capacidade funcional (Bath Ankylosing Spondylitis Functional Index – BASFI; p = 0,036). A psoríase cutânea (p < 0,001), a doença intestinal inflamatória (p = 0,023), a dactilite (p = 0,024) e o envolvimento ungueal (p = 0,004) foram mais frequentes em pacientes com EspA de início na vida adulta. Nessa grande coorte brasileira, os pacientes com EspAiJ se caracterizavam predominantemente pelo gênero masculino, envolvimento periférico (artrite e entesite), HLA-B27 positivo e escores de doença mais baixos.
Axial and peripheral involvement, enthesitis and positive HLAB27 in 60-90% children are main features of juvenile spondyloarthritis (JSpA). Radiological sacroiliitis represents an important prognostic factor that may occur within 10 years from onset.
Objectives
To determine initial and long term clinical profiles of Brazilian patients with JSpA from a single tertiary university center; the prevalence of HLAB27 and correlation with disease progression to ankylosing spondylitis (AS), according to ASAS criteria.
Methods
Descriptive cross-sectional study of a cohort of JSpA patients. All clinical demographic and radiological data were collected from chart review and HLA-B27 was analysed by flow cytometry (Becton Dickinson). Fisher and McNemar9s tests were used for statistical analyses and p<0.05 considered significant.
Results
Fifty patients with JSpA were assessed, with mean age=31.5±11.1yrs (15-60), mean age at.2±2.73yrs (7-16), mean age at diagnosis=19.8±9.0yrs (7-44) and mean disease duration=18.9±11.4yrs (3-44). The majority were males (44M:6F,88%) and whites (n=42,84%). Eleven (22%) subjects had a 1st-degree relative with SpA and 87% (34/39) were HLAB27+. At diagnosis (Table), peripheral manifestations was predominant, particularly asymmetric oligoarthritis while axial involvement was mainly inflammatory back and buttocks pain; 21 (42%) had enthesitis, all at the Achilles insertion; anterior uveitis was the major extra-articular manifestation. After a mean follow up period of 12.8±9.13yrs (1-45), 5 patients were lost, axial involvement prevailed, enthesitis remained in 13/21 and none had uveitis (Table). Radiological sacroiliitis developed in 96% (n=48) patients: 42% (n=20) ≤5yrs, 17% (n=8) within 6-10yrs and 42% (n=20) >10yrs of initial symptoms. Of note, HLA-B27+ children had earlier sacroiliitis ≤5yrs from diagnosis (p=0.02), high ESR at diagnosis (p=0.04) and developed AS (p=0.02). Regardless of daily NSAIDs therapy intake by all patients, sacroiliitis progression was not prevented (p>0.05). Sulfasalazine was used by 86% and MTX by 72%, and currently 49% patients are on anti-TNF drugs.
Conclusions
Brazilian JSpA patients are characteristically white males with initial peripheral joint and enthesitic manifestations that develop axial disease. The high prevalence of HLAB27+ in JSpA associated to early sacroiliitis, elevated ESR at diagnosis and progression to AS strengthen its role as a genetic marker of disease severity in children.
Estudos recentes relatam as características clínicas e epidemiológicas das espondiloartrites nas populações de diversos países ibero-americanos. O objetivo deste trabalho foi comparar os dados obtidos em um estudo epidemiológico brasileiro com os dados encontrados em diversos países ibero-americanos, que utilizaram um mesmo protocolo de investigação. A casuística brasileira apresentou maior frequência de pacientes com diagnóstico de espondilite anquilosante (72,3% brasileiros vs. 57,7% ibero-americanos), estando associada ao sexo masculino (73,6% vs. 66,0%) e ao antígeno de histocompatibilidade HLA-B27 positivo (65,9% vs. 51,8%). Com relação ao tratamento, os pacientes brasileiros fizeram mais uso de anti-inflamatório não hormonal (AINH) (77,0% vs. 71,2%) e menor uso de esteroides (7,5% vs. 18,5%).
Toll-like receptor (TLR) 2 and TLR4 are able to activate innate immune cells in response to gram-positive and gramnegative bacteria, respectively. Psoriatic arthritis (PsA) is a chronic inflammatory joint disease and gram-positive streptococcus may have a role in its pathogenesis, suggesting the importance of TLR2 stimulation in PsA.To assess TLR2 and TLR4 expressions on innate immune cells of PsA patients, relating to clinical disease activity.Forty-five patients with peripheral joint manifestations of PsA were included and disease activity was assessed by Disease Activity Score of 28 joint counts (DAS28). 32 healthy subjects constituted the control group. Membrane-bound TLR2 and TLR4 expressions were assessed on peripheral blood monocytes and neutrophils by flow cytometry.Twenty-seven patients had active PsA (DAS28 higher than 2.6) and 18 had inactive disease. TLR2 was significantly upregulated on monocytes in both active and inactive PsA group, comparing to healthy controls. TLR4 was similarly expressed in all tested groups.TLR2 is overexpressed by PsA monocytes, suggesting that gram-positive exposure could induce higher inflammatory responses in this disease.
To assess the sexual activity of patients with ankylosing spondylitis, correlating it with disease activity and functional indices.Thirty-two patients with ankylosing spondylitis and 32 healthy controls were assessed regarding pain, fatigue, sexual activity (by use of pictures of seven sexual positions), disease activity (by use of Bath Ankylosing Spondylitis Disease Activity Index - BASDAI), and functional capacity (by use of Bath Ankylosing Spondylitis Functional Index - BASFI). After the interview, the patients were divided into two groups: group A (with sexual activity) and group B (no sexual activity).Group B showed statistical association with longer disease duration (P = 0.01), and higher BASFI (P = 0.0007) and BASDAI (P = 0.03) scores. No correlation was observed between age and functional capacity. Man lying on his back and woman on top was the most frequent, enjoyable and least painful position. The position with the woman on her back and a man lying on top was the least chosen. Control individuals reported a higher frequency of sexual activity, longer duration of intercourse, and less pain and fatigue; the reported frequency of orgasms, however, was similar in both groups.The chronic nature of ankylosing spondylitis, with poor functional capacity and higher disease activity, interferes with sexual intercourse. When sexual activity was possible, orgasm and sexual satisfaction did not differ from those of healthy controls.
Background: Advances in pathophysiology and treatment of ankylosing spondylitis (AS) was recently demonstrated.However, the effect of anti-TNF in the newly described inflammatory pathways involved pathogenesis of this disease remains to be determined.The aim of our study was, therefore, to investigate long-term influence of anti-TNF drugs in IL-23/IL-17 axis of AS patients and their possible correlation with treatment, clinical, laboratory and radiographic parameters.Methods: Eighty-six AS anti-TNF naïve patients, 47 referred for anti-TNF therapy (active-AS; BASDAI ≥ 4) and 39 with BASDAI < 4 (control-AS) were included.The active group was evaluated at baseline, 12-months and 24-months after TNF blockade and compared at baseline to control-AS group and to 47 healthy age-and gender-matched controls.Plasma levels of IL-17A, IL-22, IL-23 and PGE2 were measured.Non-steroidal anti-inflammatory drugs (NSAIDs) intake were recorded every 6 months.Radiographic severity and progression was assessed by mSASSS at baseline and 24 months after therapy.Results: At baseline, active-AS group presented higher IL-23 and PGE2 levels compared to control-AS group (p < 0.001 and p = 0.008) and to healthy controls (p < 0.001 and p = 0.02).After 24-months of TNF blockade, IL-23 and PGE2 remained elevated with higher levels compared with the healthy group (p < 0.001 and p = 0.03) in spite of significant improvements in all clinical/inflammatory parameters (p < 0.001).Further analysis of 27 anti-TNF-treated patients who achieved a good response (ASDAS-CRP < 2.1,with a drop ≥ 1.1) at 24-months revealed that IL-23 plasma levels remained higher than healthy controls (p < 0.001) and higher than control-AS group with similar disease activity (ASDAS-CRP < 2.1, p = 0.01).In active-AS group (n = 47), there was a strong correlation between IL-23 and IL-17A at baseline, 12-months and 24-months after anti-TNF therapy (p ≤ 0.001). Conclusion:This study provides novel data demonstrating that the IL-23/IL-17 axis is not influenced by TNF blockade in AS patients despite clinical and inflammation improvements and NSAID intake.
Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) share common characteristics including the association with HLA-B27 antigen, which is positive in > 80% and 20-60% patients respectively and mostly related to axial involvement. Considerable geographical HLA-B27 prevalence in general population varies from > 50% in Canadian Indians and virtually 0% in Africans. HLAB27 may be detected by a variety of methods with similar sensibility and specificity, but different cost including serological (luminex system, solid phase assay), ADCC, molecular biology (PCR) and flow cytometry.
Objectives
To establish the prevalence of HLA-B27 in Brazilian patients with AS and PsA from a single university center using a low cost flow cytometry test.
Methods
AS and PsA patients followed at theEpA clinic from the Rheumatology Division of the Hospital das Clinicas, University of São Paulo were evaluated. HLA-B27 was analyzed in peripheral blood lymphocytes by flow cytometry using the FacsCalibur Becton/Dinkinson (BD). Fifty µl of heparinizedwhole blood from all patients and controls were incubated with 30µl HLA-B27/CD3 antibody (BD) for 30 minutes in the dark followed by red cell lysis with 2ml of lysis solution (BD). All samples were washed twice with PBS and fixed with 250µl of 1% paraformaldehyde. Statistical analysis was performed using Fisher's test and P<0.005 was considered significant.
Results
A total of 182 patients (88 AS, 94 PsA) and 72 controls were studied. Axial involvement occurred in 97% AS and 50% PsA patients, whereas 63% AS and 89% PsA had peripheral disease. HLA-B27 was positive in 83% (73/88) AS, 33% (31/94) PsA and 2.7% (2/72) controls. In AS, HLA-B27+ was associated with axial but not peripheral involvement (96%,70/73 vs61%,45/73, p= 0.047). Conversely, HLA-B27 was positive in 90% (28/31) peripheral PsA vs. 55% (17/31) axial PsA patients (p=0.003)
Conclusions
The detection of HLA-B27 by flow cytometry in Brazilian patients with AS and PsA was similar to worldwide reported prevalences proving to be a reliable inexpensive method. In AS, HLA-B27 association with axial manifestation was confirmed but in PSA, link with peripheral disease may suggest different patterns of site injury indicating that HLA-B27 testing is of little clinical value in predicting the presence of axial PsA.
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