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1.
Ann Rheum Dis ; 74(7): 1387-93, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24651623

RESUMO

OBJECTIVE: To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS). METHOD: We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon-intron boundaries, and 5 kb flanking DNA in the 5' and 3' UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p<0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into 'mild' and 'severe' groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration. RESULTS: Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10(-5)), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10(-3)). There was no observed association between radiographic severity and HLA-B*27. CONCLUSIONS: These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.


Assuntos
Reabsorção Óssea/genética , Vértebras Cervicais/diagnóstico por imagem , Estudos de Associação Genética , Vértebras Lombares/diagnóstico por imagem , Osteogênese/genética , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/genética , Adulto , Ciclo-Oxigenase 1/genética , Éxons/genética , Feminino , Genótipo , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Radiografia , Receptor Ativador de Fator Nuclear kappa-B/genética , Índice de Gravidade de Doença
2.
Clin Exp Rheumatol ; 32(3): 424-31, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24387974

RESUMO

OBJECTIVES: A significant proportion of patients with juvenile spondyloarthritis (JSpA) are refractory to treatment with established medications. The objective of this study was to assess long-term efficacy of treatment with anti-TNF agents in patients with JSpA. METHODS: An observational study of 16 patients with JSpA from 3 centres treated with infliximab (n=10) and etanercept (n=6) was performed, with a median follow-up period of 7.2 years. Prospective data was collected according to a standardized protocol. Outcomes examined were TEC, TAJC, markers of inflammation (ESR, CRP), functional assessments (C-HAQ, BASDAI, BASFI), and ongoing requirement for anti-TNF treatment. RESULTS: 13/16 patients (83%) had achieved clinical remission 6 months into the treatment. Improvement was sustained over time, with a median TAJC and TEC of 0 at any time point after 6 weeks. 6/16 patients (38%) showed a flare of arthritis after a median of 3.5 years. Two patients with hip disease prior to treatment required an arthroplasty 3 and 8 years post anti-TNF initiation. Patients showed progression of sacroiliitis with median modified New York score of 1 (range 0-3) at time of diagnosis and 3 (range 0-4) at last follow-up (p=0.002). Median BASDAI at last follow up was 1.6, median BASFI 3.1. Two patients developed transient reactions (one generalised, one local); no patient developed other adverse effects during the study. CONCLUSIONS: Anti-TNF treatment in JSpA refractory to standard treatment results in good long-term disease control except for pre-existing hip disease. However, radiographic evidence suggests inferior efficacy for control of sacroiliac joint disease.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Espondilartrite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Artrite Juvenil/tratamento farmacológico , Criança , Etanercepte , Feminino , Seguimentos , Humanos , Infliximab , Estudos Longitudinais , Masculino , Sacroileíte/tratamento farmacológico , Resultado do Tratamento
3.
Ann Rheum Dis ; 70(6): 896-904, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21540199

RESUMO

This first update of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in detail and reworded if necessary. Decisions on new recommendations were made - if necessary after voting. The strength of the recommendations (SOR) was scored on an 11-point numerical rating scale after the meeting by email. These recommendations apply to patients of all ages that fulfill the modified NY criteria for AS, independent of extra-articular manifestations, and they take into account all drug and non-drug interventions related to AS. Four overarching principles were introduced, implying that one bullet has been moved to this section. There are now 11 bullet points including 2 new ones, one related to extra-articular manifestations and one to changes in the disease course. With a mean score of 9.1 (range 8-10) the SOR was generally very good.


Assuntos
Guias de Prática Clínica como Assunto , Espondilite Anquilosante/terapia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Humanos , Cooperação Internacional , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
4.
Arthritis Rheum ; 62(5): 1298-307, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20155838

RESUMO

OBJECTIVE: Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are known triggers of reactive arthritis (ReA) and exist in a persistent metabolically active infection state in the synovium, suggesting that they may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a 6-month course of combination antibiotics is an effective treatment for patients with chronic Chlamydia-induced ReA. METHODS: This study was a 9-month, prospective, double-blind, triple-placebo trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia-induced ReA. Eligible patients had to be positive for C trachomatis or C pneumoniae by polymerase chain reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead of azithromycin; 2) azithromycin and rifampin plus placebo instead of doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin. The primary end point was the number of patients who improved by 20% or more in at least 4 of 6 variables without worsening in any 1 variable in both combination antibiotic groups combined and in the placebo group at month 6 compared with baseline. RESULTS: The primary end point was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results. Six of 27 patients (22%) randomized to combination antibiotics believed that their disease went into complete remission during the trial, whereas no patient in the placebo arm achieved remission. Significantly more patients in the active treatment group became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse events were mild, with no significant differences between the groups. CONCLUSION: These data suggest that a 6-month course of combination antibiotics is an effective treatment for chronic Chlamydia-induced ReA.


Assuntos
Artrite Reativa/tratamento farmacológico , Azitromicina/administração & dosagem , Infecções por Chlamydia/complicações , Chlamydia trachomatis/isolamento & purificação , Doxiciclina/administração & dosagem , Rifampina/administração & dosagem , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/efeitos adversos , Artrite Reativa/microbiologia , Artrite Reativa/patologia , Azitromicina/efeitos adversos , Chlamydia trachomatis/genética , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/isolamento & purificação , Doença Crônica , DNA Bacteriano/genética , Método Duplo-Cego , Doxiciclina/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Articulações/patologia , Masculino , Pessoa de Meia-Idade , Placebos , Proibitinas , Estudos Prospectivos , Rifampina/efeitos adversos , Resultado do Tratamento
5.
Ann Rheum Dis ; 69(1): 297-300, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19103635

RESUMO

OBJECTIVES: Studying post-infliximab gene expression changes could provide insights into the pathogenesis of ankylosing spondylitis (AS). METHODS: Gene expression changes were screened by microarray on peripheral blood RNA of 16 AS patients at baseline and 2 weeks post-infliximab, and selected results were confirmed by quantitative real-time (qRT)-PCR. Corresponding serum-soluble LIGHT (sLIGHT) was estimated by ELISA and the fold change in sLIGHT was correlated to the fold change in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and the Bath AS disease activity index. RESULTS: Post-infliximab, 69% of the patients (11/16) achieved an ASAS20 response. Six candidate genes were differentially expressed by microarray; four of which were validated by qRT-PCR. sLIGHT showed the most significant difference. There was good correlation of baseline sLIGHT with CRP (R = 0.60; p = 0.01) and ESR (R = 0.51; p = 0.04). The fold change in sLIGHT correlated with change in both CRP (R = 0.71, p = 0.002) and ESR (R = 0.77, p<0.001). CONCLUSION: LIGHT is significantly downregulated by infliximab. sLIGHT correlated well with changes in inflammatory markers.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Proteínas Sanguíneas/metabolismo , Espondilite Anquilosante/tratamento farmacológico , Adulto , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Índice de Gravidade de Doença , Espondilite Anquilosante/sangue , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Adulto Jovem
6.
Ann Rheum Dis ; 68(9): 1407-12, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18782793

RESUMO

OBJECTIVES: An important unresolved issue in the pathogenesis and clinical course of ankylosing spondylitis (AS) is whether juvenile-onset AS (JoAS) is a clinical entity in its own right or just an earlier onset variant of adult-onset AS (AoAS). A study was undertaken to address this issue. METHODS: All patients with AS were extracted from the database of a large spondylitis clinic. Those with symptom onset at < or =16 years were compared with those with symptom onset at > or =17 years. Odds ratios (OR) were calculated and adjusted for disease duration and current age. RESULTS: 267 patients with AS were identified; 84 met the criteria for JoAS and 183 met the criteria for AoAS. There were no differences in gender ratio (male: JoAS 81%, AoAS 79%) or in HLA-B27 status (positive: JoAS 75%, AoAS 81%). The axial/peripheral pattern of disease at presentation differed; an exclusively peripheral pattern was seen in 26% with JoAS but in only 4.6% of those with AoAS (p<0.001). There were no differences in disease activity between the two groups. When adjusted for disease duration, axial features were more prominent in AoAS than JoAS as represented by neck pain (OR 2.93 (95% CI 1.54 to 5.55)), neck stiffness (OR 3.39 (95% CI 1.80 to 6.39)), back pain (OR 2.96 (95% CI 1.43 to 6.11)) or back stiffness (OR 3.30 (95% CI 1.50 to 7.28)). AoAS was associated with worse functional and quality of life measures and higher fatigue scores when adjusted for disease duration. CONCLUSIONS: JoAS follows a distinctive clinical course from AoAS. These clinical features are dictated by factors other than male gender and HLA-B27 and warrant further investigation.


Assuntos
Espondilite Anquilosante/diagnóstico , Adolescente , Adulto , Fatores Etários , Idade de Início , Criança , Feminino , Antígeno HLA-B27/análise , Humanos , Masculino , Prognóstico , Qualidade de Vida , Radiografia , Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/patologia , Adulto Jovem
7.
Clin Exp Rheumatol ; 27(4 Suppl 55): S26-32, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19822042

RESUMO

Ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are immune-mediated inflammatory joint diseases with the potential for significant target organ damage. Genetic factors play an important role in defining disease susceptibility. Both diseases are mediated in part by TNF, since anti-TNF therapies have proved effective in both AS and RA. Despite their similarities, the genetic elements associated with the respective diseases differ, most notably in HLA associations, with AS being associated with class I HLA alleles and RA associated with class II HLA alleles. AS has a predilection for axial joints whereas RA targets peripheral joints, but the immunological basis of that distinction is unknown. Autoantibody formation is the immunological hallmark of RA, whereas AS is notable for being a "seronegative" disease. Growing knowledge of new aspects of the host immune response (such as innate immune responses and Th17 cells) is adding to new insights into shared mechanisms of pathogenesis between these two diseases.


Assuntos
Artrite Reumatoide/imunologia , Imunidade Inata/imunologia , Espondilite Anquilosante/imunologia , Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Autoanticorpos/sangue , Genes MHC Classe I , Genes MHC da Classe II , Humanos , Espondilite Anquilosante/sangue , Espondilite Anquilosante/genética
8.
Ann Rheum Dis ; 67(3): 346-52, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17967833

RESUMO

OBJECTIVE: Evaluate long-term safety and efficacy of etanercept treatment in patients with ankylosing spondylitis (AS). METHODS: Patients with AS who previously participated in a randomised controlled trial (RCT) of etanercept were eligible to enroll in a 168-week open-label extension (OLE). Safety end points included rates of adverse events (AE), serious adverse events (SAE), infections, serious infections and death. Efficacy end points included Assessment in Ankylosing Spondylitis (ASAS20) response, ASAS 5/6 response and partial remission rates. RESULTS: A total of 257 of 277 patients (92%) enrolled in the OLE. After up to 192 weeks of treatment with etanercept, the most common AEs were injection site reactions, headaches and diarrhoea. The exposure-adjusted rate of SAEs was 0.08 per patient-year. The rate of infections was 1.1 per patient-year, and the rate for serious infections was 0.02 per patient-year. No deaths were reported. Of patients who received etanercept in both the RCT and OLE and were still in the trial, 71% were ASAS20 responders at week 96, and 81% were responders at week 192. ASAS 5/6 response rates were 61% at week 96 and 60% at week 144, and partial remission response rates were 41% at week 96 and 44% at week 192. Placebo patients who switched to etanercept in the OLE showed similar patterns of efficacy maintenance. CONCLUSIONS: Etanercept was well tolerated for up to 192 weeks in patients with AS, with no unexpected AEs or SAEs observed. No deaths were reported. Improvements in the signs and symptoms of AS were maintained for up to 192 weeks.


Assuntos
Antirreumáticos/uso terapêutico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Adulto , Antirreumáticos/efeitos adversos , Método Duplo-Cego , Etanercepte , Feminino , Seguimentos , Humanos , Imunoglobulina G/efeitos adversos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
9.
Rheumatology (Oxford) ; 47(8): 1213-8, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18539622

RESUMO

OBJECTIVES: Many AS patients report periods of perceived higher disease activity (flares). This pilot study aims to document disease activity patterns reported by AS patients and examine associations with disease-specific health status measures. METHODS: Consecutive AS patients (n = 114) were asked whether they experience flares, and if they experience symptoms of AS between flares. They were shown the Flare Illustration of disease patterns over time and asked to select the pattern that best described their disease (i) since symptom onset and (ii) in the past year. Associations between reported disease pattern and disease activity (Bath AS Disease Activity Index, BASDAI); functional impairment (Bath AS Functional Index, BASFI); AS Quality of Life (ASQoL); Back Pain (Nocturnal and Overall) and demographic features were assessed in a subsample (n = 83) (statistical significance defined at P 70% of patients) and patterns with constant symptoms since onset (vs intermittent symptoms) were associated with worse health status (ASQoL: P = 0.007; BASDAI: P = 0.029; BASFI: P = 0.013, overall back pain: P = 0.025). CONCLUSIONS: Almost all AS patients report flares in disease activity: 70-80% report constant symptoms with single/repeated flares, while 20-30% report flares with no intermittent symptoms. The former is associated with a significantly poorer health status. These findings will be validated in a prospective study.


Assuntos
Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico , Adulto , Idoso , Dor nas Costas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Periodicidade , Projetos Piloto , Psicometria , Qualidade de Vida , Espondilite Anquilosante/complicações
10.
Clin Exp Rheumatol ; 26(1 Suppl 48): S12-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18570749

RESUMO

Autoimmune rheumatic diseases are generally considered as a multifactorial aetiology, mainly genetic susceptibility combined with environmental triggers of which bacteria are considered one of the most prominent. Among the rheumatic diseases where bacterial agents are more clearly involved as triggers are: reactive arthritis (ReA), rheumatic fever (RF) and Lyme disease. The role of bacterial infections in inducing other seronegative spondyloarthritis and antiphospholipid antibody syndrome has been hypothesized but is still not proven. The classic form of ReA is associated with the presence of HLA-B27 and is triggered by the urethritis or enteritis causing pathogens Chlamydia trachomatis and the enterobacteria Salmonella, Shigella, and Yersinia, respectively. But several other pathogens such as Brucella, Leptospira, Mycobacteria, Neisseria, Staphylococcus and Streptococcus have also been reported to cause ReA. RF is due to an autoimmune reaction triggered by an untreated throat infection by Streptococcus pyogenes in susceptible individuals. Carditis is the most serious manifestation of RF and HLA-DR7 is predominantly observed in the development of valvular lesions. Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Knowledge is limited about how this spirochete interacts with human tissues and cells. Some data report that Borrelia burgdorferi can manipulate resident cells towards a pro- but also anti-inflammatory reaction and persist over a long period of time inside the human body or even inside human cells.


Assuntos
Doenças Autoimunes/microbiologia , Infecções Bacterianas/complicações , Infecções Bacterianas/imunologia , Doenças Reumáticas/imunologia , Doenças Reumáticas/microbiologia , Doenças Autoimunes/imunologia , Humanos , Proibitinas
11.
J Clin Invest ; 102(10): 1776-82, 1998 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-9819362

RESUMO

The basic mechanisms underlying reactive arthritis and specifically the joint injury that follows intra-articular Chlamydia trachomatis infection have not been defined. The present study addresses this question through the development of an experimental model. Stable cell lines were generated from synoviocytes harvested from the knee joints of Lewis rats. The synoviocytes were cocultivated with C. trachomatis to allow invasion by the microbe and were then transferred by intra-articular injection into the knee joints of Lewis rats. The ensuing arthritis could be subdivided into an early phase (

Assuntos
Artrite Reativa/microbiologia , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis , Membrana Sinovial/microbiologia , Animais , Artrite Reativa/metabolismo , Artrite Reativa/patologia , Proteínas da Membrana Bacteriana Externa/análise , Western Blotting , Infecções por Chlamydia/metabolismo , Infecções por Chlamydia/patologia , Chlamydia trachomatis/isolamento & purificação , Doença Crônica , Ciprofloxacina/uso terapêutico , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Injeções Intra-Articulares , Injeções Intramusculares , Injeções Subcutâneas , Lipopolissacarídeos/análise , Masculino , Microscopia de Fluorescência , Ratos , Ratos Endogâmicos Lew , Baço/metabolismo , Baço/microbiologia , Membrana Sinovial/citologia , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Tetraciclina/uso terapêutico , Fatores de Tempo
12.
J Clin Invest ; 63(4): 627-36, 1979 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-438327

RESUMO

Using the Cowan I strain of Staphylococcus aureus, we compared the binding properties of human monomeric immunoglobulin (Ig)G and oligomeric or complexed IgG. Heat-aggregated IgG served as a model for complexed IgG and heat-killed, formalin-fixed S. aureus (StaphA) as a cellular receptor for IgG, in determining the parameters for oligomeric and monomeric binding. Because of its capacity for multipoint attachment, complexed IgG binding was favored over monomeric IgG binding, and this preferential binding was demonstrated kinetically in equivalent forward rates of binding but in a much slower rate of release from StaphA receptors. From binding studies, we determined which conditions maximize complexes IgG binding and minimized monomeric IgG binding and applied them to the development of an assay for aggregated IgG and immune complexes in human sera. The StaphA binding assay that was devised is quantitative, sensitive, and not complement dependent. It is relatively unaffected by factors such as heparin, complement fixation, native antibodies, and immunoglobulin concentrations, but is affected by the presence of rheumatoid factors. It compares favorably with two other complement-dependent assays of immune complexes, the 125I-Clq binding assay and the Raji cell assay, in terms of sensitivity and the size of immune complexes detected. Studies on the potential of the assay for detecting, isolating, and characterizing immune complexes in biological fluids are presented.


Assuntos
Complexo Antígeno-Anticorpo , Imunoglobulina G , Proteína Estafilocócica A , Staphylococcus aureus/imunologia , Humanos , Soros Imunes , Imunoglobulina G/metabolismo , Imunoglobulina M , Cinética , Substâncias Macromoleculares , Testes de Precipitina , Proteína Estafilocócica A/metabolismo
13.
J Clin Invest ; 86(4): 1193-203, 1990 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2212008

RESUMO

We previously reported elevated serum antibody levels to a peptide representing the HLA-B27 polymorphic region (B27 peptide) in HLA-B27(+) ankylosing spondylitis (AS) patients. A plasmid (pHS-2) isolated from arthritogenic Shigella flexneri strains had been shown to encode an amino acid sequence homologous to HLA-B27. Rabbit antibody to this sequence (pHS-2 peptide) strongly cross-reacted with B27 peptide and, to a much lesser extent, with Klebsiella nitrogenase peptide. Serum antibody levels to pHS-2 peptide were studied in 160 spondylarthropathy patients. 12 of 115 (10.4%) AS patients, 2 of 45 (4.4%) patients with Reiter's syndrome or reactive arthritis as well as 6 of 147 (4.1%) normal controls were shown to have elevated anti-pHS-2 peptide antibodies. Antibody levels to B27 and pHS-2 peptides were significantly correlated in 134 HLA-B27(+) patients (r = 0.333, P less than 0.001). 13 of 15 affinity-purified anti-B27 peptide antibodies from patients strongly cross-reacted with pHS-2 peptide, whereas only 3 weakly cross-reacted to nitrogenase peptide. Leucine appeared to be a critical residue for this cross-reaction. AS patients' anti-B27 peptide antibodies reacted with HLA-B27 transfected L cells. These results may suggest that pHS-2 peptide more efficiently "mimics" B27 peptide than does nitrogenase peptide. Involvement of pHS-2 in pathogenesis of spondylarthropathy through molecular mimicry mechanisms requires further study.


Assuntos
Artrite Infecciosa/imunologia , Autoanticorpos/análise , Antígeno HLA-B27/imunologia , Plasmídeos , Shigella flexneri/genética , Sequência de Aminoácidos , Animais , Autoanticorpos/imunologia , Reações Cruzadas , Feminino , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Coelhos , Espondilite Anquilosante/etiologia
14.
J Clin Invest ; 70(2): 271-80, 1982 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6808025

RESUMO

The presence of circulating immune complexes (IC) in patients with infective endocarditis has been well documented but the contributions of host and bacterial components to these IC have not been defined. To study this question, IC were isolated from serum of a patient with Streptococcus faecalis endocarditis by differential polyethylene glycol precipitation and competitive binding to staphylococcal protein A. A rabbit antiserum raised against the purified IC had reactivity by crossed immunoelectrophoresis primarily with an antigen derived from the cytoplasm of the infective organism. The antigen was a protein with a 12,000-dalton molecular mass. In situ radiolabeling of the IC bound to the protein A demonstrated a component of the same molecular mass as the bacterial antigen recognized by the antiserum. The patient serum had multiple antibody specificities reactive with bacterial antigens, including the antigen recognized by the rabbit anti-IC antiserum. These techniques for isolation and characterization of circulating IC may have value in the study of IC diseases in which the inciting antigens are not known.


Assuntos
Complexo Antígeno-Anticorpo/análise , Antígenos de Bactérias/análise , Endocardite Bacteriana/imunologia , Animais , Eletroforese em Gel de Poliacrilamida , Enterococcus faecalis , Humanos , Imunoeletroforese Bidimensional , Peso Molecular , Coelhos , Proteína Estafilocócica A/metabolismo , Infecções Estreptocócicas/imunologia
15.
Arch Intern Med ; 142(10): 1813-5, 1982 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7125767

RESUMO

Sixteen men with systemic lupus erythematosus (SLE) were examined to assess their genetic and hormonal status. The results of buccal smears in 13 patients examined were normal. Hormonal profiling was done in eight patients receiving no steroid therapy. Four patients had elevated plasma estradiol levels (30, 35, 55, and 103 pg/mL; normal, 12 to 23 pg/mL) and elevated plasma estrone levels (115, 150, 155, and 160 pg/mL; normal, 48 to 100 pg/mL). One patient had a decreased serum testosterone level (134 ng/dL; normal, 300 to 1,000 ng/dL), with an elevated luteinizing hormone (LH) level (4.2 ng/mL; normal, 1.6 to 4.0 ng/mL). One patient had an elevation in both levels of serum follicle-stimulating hormone (17.6 ng/mL; normal, 1 to 5 ng/mL) and LH (10.0 ng/mL). Two patients given infusions of 3H-androstenedione and 14C-testosterone had normal findings from kinetic studies of these hormones. Hyperestrogenemia and hypoandrogenemia observed in some men with SLE suggest that female sex hormones may create an immunologic milieu that facilitates the autoimmune phenomena.


Assuntos
Androgênios/sangue , Estrogênios/sangue , Lúpus Eritematoso Sistêmico/sangue , Hormônios Adeno-Hipofisários/sangue , Adolescente , Adulto , Idoso , Humanos , Lúpus Eritematoso Sistêmico/genética , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/ultraestrutura , Cromatina Sexual/ultraestrutura , Fatores Sexuais
16.
Medicine (Baltimore) ; 61(1): 25-32, 1982 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-6173564

RESUMO

A retrospective study was undertaken of patients with systemic lupus erythematosus in whom serum amylase had been determined. Sixty-three patients were identified, and of these 53 had abdominal pain at the time of the amylase measurement. Twenty-seven (51 percent) had a normal serum amylase, and 12 of this group had defined reasons for the abdominal pain. Of the 26 patients with hyperamylasemia, 6 had extrapancreatic causes for the elevated amylase. In 20 patients (37 percent of those with abdominal pain) the clinical diagnosis of pancreatitis was made. The amylase levels showed no correlation with renal function nor with dose of corticosteroid. Four patients with pancreatitis were identified in whom no contributing factor other than SLE could be ascertained. No serious complication of the pancreatitis was seen, and recovery occurred despite continued steroid therapy. Pancreatitis is not a rare occurrence in SLE, and may be related in part to the vasculitis seen during periods of disease activity.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Pancreatite/etiologia , Doença Aguda , Adolescente , Adulto , Idoso , Amilases/sangue , Azatioprina/uso terapêutico , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pseudocisto Pancreático/diagnóstico , Pancreatite/diagnóstico , Prednisona/uso terapêutico
17.
Am J Med ; 75(5): 785-9, 1983 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-6605683

RESUMO

IgA and IgM rheumatoid factor activity, circulating immune complex levels, and antinuclear antibodies were measured in 17 patients with subacute or chronic infective endocarditis. Approximately three fourths of these patients had both IgA and IgM rheumatoid factors detectable by radioimmunoassay, and IgA and IgM rheumatoid factor activity was strongly correlated (p less than 0.01). In three patients studied, IgA rheumatoid factor activity was predominantly polymeric as assessed by sucrose density ultracentrifugation (55 to 92 percent of total rheumatoid factor activity) and could bind radiolabeled secretory component. No correlations between rheumatoid factor activity and circulating immune complex levels or antibodies to nuclear antigens were observed. These observations indicate that circulating polymeric IgA antibodies do not necessarily signify a mucosal stimulus for IgA production and also demonstrate differences in the intensity and spectrum of autoantibody production when compared with autoimmune diseases.


Assuntos
Endocardite Bacteriana/imunologia , Imunoglobulina A/análise , Fator Reumatoide/análise , Adulto , Idoso , Anticorpos Antinucleares/análise , Complexo Antígeno-Anticorpo/análise , Autoanticorpos/biossíntese , Doenças Autoimunes/imunologia , Feminino , Humanos , Imunoglobulina M/análise , Masculino , Pessoa de Meia-Idade
18.
Am J Med ; 98(1): 13-21, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7825614

RESUMO

PURPOSE: To define the natural history of post-Salmonella-infection reactive arthritis (ReA) in a point source cohort concurrently exposed to the same microorganism, and to determine any relationship between anti-Salmonella humoral immune response to the organism and clinical outcome at 5 years. PATIENTS AND METHODS: A cohort of 423 Ontario Provincial Police officers with a clinical diagnosis of Salmonella food poisoning were defined in 1984. Five years following the food poisoning, a mail and telephone survey was carried out to determine all those who developed ReA within 3 months of the onset of dysentery. Medical and physiotherapy charts from an earlier study on the same cohort were incorporated. All patients with a history compatible with reactive arthritis were interviewed and examined. Serum was taken to determine the presence of isotypic antibodies to the lipopolysaccharide of the causative Salmonella typhimurium. RESULTS: Twenty-seven of the 423 individuals with dysentery were identified as developing acute ReA. In one third of them, the arthritis resolved within 4 months of onset. Two thirds continued to have subjective complaints, mostly of minor significance. However, symptoms were severe enough to force a change in work for 4 patients. Another 4 patients had objective damage to joints radiographically. Objective changes to joints were documented on physical examination in 37% of ReA patients 5 years following onset of disease. IgA antilipopolysaccharide antibodies correlated with the severity and duration of disease. Tests of cellular immune function did not correlate with clinical variables. CONCLUSIONS: Chronic symptoms persist 5 years after the onset of ReA in the majority of patients. Joint damage by physical examination and radiographic assessment correlate with functional disability. Some early clinical features of disease, including prolonged diarrhea during the acute illness, may predict a worse outcome. IgA antilipopolysaccharides may serve as a disease marker for late post-Salmonella-infection ReA.


Assuntos
Anticorpos Antibacterianos/sangue , Artrite Reativa/imunologia , Antígenos HLA-B/genética , Imunoglobulina A/sangue , Intoxicação Alimentar por Salmonella/complicações , Salmonella typhimurium/imunologia , Doença Aguda , Adulto , Análise de Variância , Artrite Reativa/microbiologia , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Gastroenterite/complicações , Gastroenterite/microbiologia , Antígenos HLA-B/sangue , Humanos , Lipopolissacarídeos/imunologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Proibitinas , Intoxicação Alimentar por Salmonella/microbiologia , Salmonella typhimurium/genética
19.
Am J Med ; 77(1): 47-53, 1984 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6741983

RESUMO

A one-year experience with prosthetic joint infection, in which 63 cases were identified, is reviewed. Thirty cases (48 percent) were early infections, in the first postoperative year, and 33 cases (52 percent) were late, occurring more than one year after implantation. Pain was the predominant symptom, but clinical clues suggesting infection were frequently absent, with fever in 43 percent and leukocytosis in only 10 percent. The radiographic appearance was more frequently abnormal in late infections (67 versus 37 percent, p less than 0.02). Staphylococci were predominant organisms, constituting 59 percent of prosthetic joint infections, and S. epidermidis was the predominant species in both early and later infections. Of the hematogenous infections, 11 of 13 occurred in the group with late infections; these were mostly nonstaphylococcal . Antigenic proteins of S. epidermidis were characterized by gel electrophoresis, but no infection-specific antigens could be identified when patient serum was compared with normal samples. Precipitating antibodies to the extracellular proteins of S. epidermidis were present in 50 percent of patients with S. epidermidis prosthetic joint infections, 27 percent of patients with nonstaphylococcal infections, 20 percent of patients with S. aureus infections, and 11 percent of normal subjects. In view of the increasing importance of prosthetic joint infection, further study of the pathogenesis of the infection and the host immune response is warranted.


Assuntos
Infecções Bacterianas/microbiologia , Prótese de Quadril/efeitos adversos , Artropatias/microbiologia , Prótese do Joelho/efeitos adversos , Adulto , Idoso , Bactérias/isolamento & purificação , Infecções Bacterianas/etiologia , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Artropatias/etiologia , Masculino , Pessoa de Meia-Idade
20.
Am J Med ; 70(4): 817-24, 1981 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6971057

RESUMO

To determine guidelines for treatment with high-dose intravenous methylprednisolone in lupus nephritis, we prospectively assessed the response to pulse therapy in 34 patients. In 12 of them, serum creatinine decreased by at least 20 percent within two months of treatment whereas in the remaining 22 there was no such response. Patients who responded were characterized by recent deterioration in function whereas nonresponders had had a more stable antecedent course (p = 0.003). Responders also had more diffuse lesions on renal biopsy (p = 0.028), had higher levels of anti-DNA antibodies (p less than 0.05), and tended to have higher titers of immune complexes and lower total hemolytic complement. High-dose intravenous methylprednisolone therapy may lead to striking improvement in renal function in lupus nephritis, especially in the subset of patients with recent antecedent functional deterioration. This improvement was maintained in 60 percent of the patients who responded for at least six months.


Assuntos
Lúpus Eritematoso Sistêmico/tratamento farmacológico , Metilprednisolona/administração & dosagem , Adolescente , Adulto , Anticorpos Anti-Idiotípicos/análise , Complexo Antígeno-Anticorpo/análise , Creatinina/sangue , DNA/imunologia , Avaliação de Medicamentos , Feminino , Humanos , Infusões Parenterais , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Nefrite/tratamento farmacológico , Nefrite/imunologia , Estudos Prospectivos
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