The role of KIR2DL3/HLA-C*0802 in Brazilian patients with rheumatoid vasculitis

OBJECTIVES: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis. METHODS: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers). RESULTS: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found. CONCLUSION: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions

A narrativa como um dispositivo na elaboração de um novo olhar sobre o câncer infantil

Há anos o câncer vem se destacando como a doença mais temida pela sociedade. É notável o estigma e a exclusão que tal patologia tem gerado atualmente. Além de todo o sofrimento biológico, há por trás de qualquer paciente terminal uma profunda dor emocional e psicológica. Quando se trata de crianças, há uma potencialização do sofrimento diante da proximidade da morte que se mostra de maneira tão precoce na vida do ser humano. Infelizmente, a técnica utilizada no tratamento oncológico só tende a aumentar esse sofrimento, por se tratar de uma técnica invasiva e dolorosa, deixando crianças ainda mais frágeis. Aliado a essa técnica penosa, a criança é submetida a um processo de adaptação que compromete todo o seu desenvolvimento. O paciente se vê diante de uma nova realidade, um novo mundo para o qual não estava preparado, e que por isso, vem alterar o seu “jeito criança de ser e estar no mundo”.Segundo Huizinga (2008), o jogo e as brincadeiras são uma forma de manifestação cultural, além de ser considerado algo inato ao ser humano. A brincadeira é algo muito presente no cotidiano das crianças, em especial, já que elas vivem em um mundo de fantasia, no qual realidade e “faz?de?conta” se confundem. Esse projeto busca utilizar do lúdico como uma ferramenta de linguagem da criança, e também como potencializador do aprendizado da criança e despertando sentimentos positivos que ajudem o paciente a enfrentar as adversidades da doença e do seu tratamento. Utilizaremos para isso, o encontro com o paciente como um dispositivo que aumente o poder de ação da criança por meio da alegria. Utiliza?se uma linguagem não verbal como forma de expressão, na qual a realidade é percebida pelos sentidos, não necessitando de explicação lógica para existir

A narrativa como um dispositivo na elaboração de um novo olhar sobre o câncer infantil

Há anos o câncer vem se destacando como a doença mais temida pela sociedade. É notável o estigma e a exclusão que tal patologia tem gerado atualmente. Além de todo o sofrimento biológico, há por trás de qualquer paciente terminal uma profunda dor emocional e psicológica. Quando se trata de crianças, há uma potencialização do sofrimento diante da proximidade da morte que se mostra de maneira tão precoce na vida do ser humano. Infelizmente, a técnica utilizada no tratamento oncológico só tende a aumentar esse sofrimento, por se tratar de uma técnica invasiva e dolorosa, deixando crianças ainda mais frágeis. Aliado a essa técnica penosa, a criança é submetida a um processo de adaptação que compromete todo o seu desenvolvimento. O paciente se vê diante de uma nova realidade, um novo mundo para o qual não estava preparado, e que por isso, vem alterar o seu “jeito criança de ser e estar no mundo”.Segundo Huizinga (2008), o jogo e as brincadeiras são uma forma de manifestação cultural, além de ser considerado algo inato ao ser humano. A brincadeira é algo muito presente no cotidiano das crianças, em especial, já que elas vivem em um mundo de fantasia, no qual realidade e “faz?de?conta” se confundem. Esse projeto busca utilizar do lúdico como uma ferramenta de linguagem da criança, e também como potencializador do aprendizado da criança e despertando sentimentos positivos que ajudem o paciente a enfrentar as adversidades da doença e do seu tratamento. Utilizaremos para isso, o encontro com o paciente como um dispositivo que aumente o poder de ação da criança por meio da alegria. Utiliza?se uma linguagem não verbal como forma de expressão, na qual a realidade é percebida pelos sentidos, não necessitando de explicação lógica para existir

Human MMP28 expression is unresponsive to inflammatory stimuli and does not correlate to the grade of intervertebral disc degeneration

BACKGROUND: MMP28 (epilysin) is a recently discovered member of the MMP (matrix metalloproteinase) family that is, amongst others, expressed in osteoarthritic cartilage and intervertebral disc (IVD) tissue. In this study the hypothesis that increased expression of MMP28 correlates with higher grades of degeneration and is stimulated by the presence of proinflammatory molecules was tested. Gene expression levels of MMP28 were investigated in traumatic and degenerative human IVD tissue and correlated to the type of disease and the degree of degeneration (Thompson grade). Quantification of MMP28 gene expression in human IVD tissue or in isolated cells after stimulation with the inflammatory mediators lipopolysaccharide (LPS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α or the histondeacetylase inhibitor trichostatin A was performed by real-time RT PCR. RESULTS: While MMP28 expression was increased in individual cases with trauma or disc degeneration, there was no significant correlation between the grade of disease and MMP28 expression. Stimulation with LPS, IL-1β, TNF-α or trichostatin A did not alter MMP28 gene expression at any investigated time point or any concentration. CONCLUSIONS: Our results demonstrate that gene expression of MMP28 in the IVD is not regulated by inflammatory mechanisms, is donor-dependent and cannot be positively or negatively linked to the grade of degeneration and only weakly to the occurrence of trauma. New hypotheses and future studies are needed to find the role of MMP28 in the intervertebral disc

Association of HLA-DRB5*01 with protection against cutaneous manifestations of rheumatoid vasculitis in Brazilian patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Objective: To evaluate the frequency of HLA classes I and II and their association with the cutaneous manifestation of rheumatoid vasculitis (RV) in Brazilian patients. Patients and methods: During one year we selected 130 patients with rheumatoid arthritis (RA) classified according to the American College of Rheumatology, 1987. All patients underwent a clinical and laboratory questionnaire to exclude other causes of cutaneous vasculopathy (neoplasia, infections, illicit drug use, diabetes mellitus, and tobaccoism). Seventy-three patients with any risk factor for other causes of vasculopathy were excluded. Fifty-seven without risk factors for other causes of vasculopathy were included in the study, 17 with RV according to Scott and Bacon's criteria, 1984. Demographic data, time of RA diagnosis, disease activity (DAS28), presence of rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were analyzed. The HLA alleles were typed using the DNA-amplified polymerase chain reaction with low-resolution hybridization and sequence-specific primers. Results: The comparison between the 40 patients without RV and the 17 patients with RV showed an increased frequency of HLAB*14 (Pc = 0.168) and HLA-Cw*08 (Pc = 0.084) in patients with RV and an increased frequency of HLA-DRB5*01 (Pc = 0.048) in patients without RV. Conclusion: The HLA-DRB5*01 may confer protection against that extra-articular manifestation of RA.523366374Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Associação do HLA-DRB5*01 com proteção contra manifestação cutânea da vasculite reumatoide em pacientes brasileiros

OBJETIVO: Avaliar a frequência do HLA classes I e II e sua associação com a manifestação cutânea da vasculite reumatoide (VR) em pacientes brasileiros. PACIENTES E MÉTODOS: Durante um ano foram selecionados 130 pacientes com artrite reumatoide (AR), classificados de acordo com os critérios do American College of Rheumatology de 1987. Os pacientes foram submetidos a um questionário clínico e laboratorial para exclusão de outras causas de vasculopatia cutânea (neoplasia, infecções, uso de drogas ilícitas, diabetes mellitus e tabagismo). Setenta e três foram excluídos por apresentarem algum fator de risco para outras causas de vasculopatias. Cinquenta e sete foram incluídos no estudo sem fator de risco para outras causas de vasculopatia, dos quais 17 apresentavam VR de acordo com os critérios de 1984 de Scott e Bacon. Foram analisados dados demográficos, tempo de diagnóstico de AR, atividade da doença (DAS28) e presença de fator reumatoide e de anticorpos antipeptídeo citrulinado cíclico. Alelos HLA foram tipificados usando-se a reação em cadeia da polimerase-DNA amplificada por hibridização de baixa resolução com sequências específicas de sondas. RESULTADOS: A comparação entre os 40 pacientes sem VR e os 17 pacientes com VR demonstrou uma frequência aumentada do HLA-B*14 (Pc = 0,168) e do HLA-Cw*08 (Pc = 0,084) em pacientes com VR, e uma frequência aumentada do HLA-DRB5*01 (Pc = 0,048) em pacientes sem VR. CONCLUSÃO: O HLA-DRB5*01 pode conferir proteção contra essa manifestação extra-articular da AR

Association Of Hla-drb5*01 With Protection Against Cutaneous Manifestations Of Rheumatoid Vasculitis In Brazilian Patients.

To evaluate the frequency of HLA classes I and II and their association with the cutaneous manifestation of rheumatoid vasculitis (RV) in Brazilian patients. During one year we selected 130 patients with rheumatoid arthritis (RA) classified according to the American College of Rheumatology, 1987. All patients underwent a clinical and laboratory questionnaire to exclude other causes of cutaneous vasculopathy (neoplasia, infections, illicit drug use, diabetes mellitus, and tobaccoism). Seventy-three patients with any risk factor for other causes of vasculopathy were excluded. Fifty-seven without risk factors for other causes of vasculopathy were included in the study, 17 with RV according to Scott and Bacon's criteria, 1984. Demographic data, time of RA diagnosis, disease activity (DAS28), presence of rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were analyzed. The HLA alleles were typed using the DNA-amplified polymerase chain reaction with low-resolution hybridization and sequence-specific primers. The comparison between the 40 patients without RV and the 17 patients with RV showed an increased frequency of HLA-B*14 (Pc = 0.168) and HLA-Cw*08 (Pc = 0.084) in patients with RV and an increased frequency of HLA-DRB5*01 (Pc = 0.048) in patients without RV. The HLA-DRB5*01 may confer protection against that extra-articular manifestation of RA.52366-7

HLA-DR in Brazilian patients with polyarteritis nodosa (PAN) and microscopic polyangiitis (MPA)

The aim of this study was to evaluate the frequency and clinical associations of HLA-DR alleles in Brazilian Caucasian patients with polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA). We evaluated 29 Caucasian patients with vasculitis classified as PAN or MPA according to the American College of Rheumatology (ACR) 1990 Criteria, Chapel Hill Consensus Conference (CHCC) nomenclature for vasculitis and EULAR recommendations for conducting clinical studies in systemic vasculitis. HLA-DR alleles were typed using polymerase chain reaction-amplified DNA, hybridized with sequence-specific low resolution primers. DNA obtained from 59 Caucasian healthy blood donors were used as control. In order to evaluate if a specific HLA may have influence on the clinical profile of those diseases, we also divided the patients according to Birmingham vasculitis score (BVAS) and Five-Factors Score (FFS) at the time of diagnosis. Increased frequency of HLA-DRB1*16 (p = 0.023) and DRB4*01 (p = 0.048) was found in patients with higher disease activity at the time of diagnosis (BVAS >= 22). Patients with less severe disease (FFS = 0) had a higher frequency of HLA-DRB1*03 (p = 0.011). Patients with gastrointestinal tract involvement had significantly increased frequency of HLA-DRB1*11 or B1*12 (p = 0.046), B1*13 (p = 0.021) and B3 (p = 0.008). In contrast, patients with renal disease, had higher frequency of DRB1*15 or DRB1*16 (p = 0.035) and B5 (p = 0.035). In the subgroup of patients with MPA, increased frequency of HLA-DRB1*15 was found in patients with BVAS >= 22 (p = 0.038) and FFS >= 1 (p = 0.039) suggesting that this allele is associated with more aggressive disease. Antineutrophil cytoplasmic antibodies (ANCA) negative MPA patients had significantly increased frequency of HLA-DRB1*11 or DRB1*12 when compared to ANCA positive patients (p = 0.023). Our results suggest that HLA-DR alleles may influence PAN and MPA clinical expression and outcome and that in MPA they participate in the mechanisms involved in the development to ANCA.Cleide Moreira Silva and Helymar da Costa MachadoFAEPEX-UNICAM

Undifferentiated Spondyloarthritis: A Longterm Followup

Objective. To analyze the longterm followup of a series of Brazilian patients with undifferentiated spondyloarthritis (uSpA). Methods. Prospective study analyzing a group of 111 patients with the diagnosis of uSpA, fulfilling the European Spondylarthropathy Study Group and the Amor criteria, who were followed for 5 to 10 years in a single university referral center. Patients had their outcome analyzed at 5, 7, and 10 years. Results. There was a predominance of men (81.1%), white ethnicity (78.4%), and positive HLA-B27 (61.3%), with a mean age at onset of 27.2 years. Twenty-seven patients presented development to ankylosing spondylitis (AS; 24.3%) and 3 to psoriatic arthritis (PsA; 2.7%), while 25 patients (22.5%) went into remission during the followup. Univariate logistic regression analysis revealed that ethnicity, HLA-B27, buttock pain, inflammatory low back pain, ankle involvement, grade I sacroiliitis at the beginning of the study, and the use of sulfasalazine were statistically associated with progression to AS. Multivariate logistic regression analysis revealed that HLA-B27 (p = 0.035, OR 6.720.95% CI 11.45-39.43) and buttock pain (p = 0.009, OR 6.211, 95% CI 1.591-24.25) were statistically associated with progression to AS. Conclusion. In a longterm followup of 111 Brazilian patients with uSpA, HLA-B27 and buttock pain were significant predictors of progression to a definite disease. (First Release May 1 2010; J Rheumatol 2010;37:1195-9; doi:10.3899/jrheum.090625)FAPESP Fundação de Amparo à Pesquisa do Estado de São Paul