RESUMEN
An accurate dissection of peripheral blood enumeration is lacking in primary Sjögren's syndrome (pSS). The purpose of this study was to quantify different leucocyte populations in peripheral blood of patients with pSS. Numbers of specific leucocyte subsets were determined in 86 pSS patients and 74 healthy donors quantifying 21 distinct subtypes by flow cytometry. Subgroups of pSS patients were stratified based on presence of extraglandular manifestations (EGMs) and SSA/SSB autoantibodies. Overall, pSS patients manifested decreased lymphocyte subpopulations compared to healthy donors. Such decreases were more pronounced in SSA/SSB positive patients and patients with EGM. Granulocyte and monocyte subpopulations were increased in pSS patients compared to healthy donors, with the greatest increases in SSA/SSB positive patients. Unsupervised hierarchal clustering based on cell quantities was used to further subgroup the pSS patients into four clusters. One of the clusters characterized by higher concentrations of NKT cells, CD56hi NK cells, CD20+ CD38- B cells and CD8+ CD38- T cells was associated with weaker clinical symptoms than the other clusters, possibly marking a milder disease phenotype. In conclusion, our analyses indicate significant alterations in the cellular profiles of peripheral blood leucocytes in patients with pSS and may help to stratify the patients according to disease severity.
Asunto(s)
Granulocitos/inmunología , Linfocitos/inmunología , Monocitos/inmunología , Síndrome de Sjögren/inmunología , Anciano , Anticuerpos Antinucleares/sangre , Antígenos CD/metabolismo , Circulación Sanguínea , Análisis por Conglomerados , Progresión de la Enfermedad , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Sjögren/patologíaRESUMEN
OBJECTIVES: The pro-inflammatory proteins calprotectin (a heterocomplex of S100A8/A9) and S100A12 have been associated with disease activity in rheumatoid arthritis (RA). The aim of this study was to compare their potential as biomarkers in a prospective study of RA patients starting with infliximab as their first biological disease-modifying anti-rheumatic drug (DMARD). METHOD: Thirty-nine RA patients were examined and serum samples collected when starting with infliximab and after 3, 6, and 12 months. Calprotectin and S100A12 were analysed by enzyme-linked immunosorbent assays (ELISAs) and, together with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), measured at all time points. A disease activity score of 28 joints (DAS28) was calculated. Radiographs of the hands, wrists, and feet were taken at baseline and after 3 years, and assessed according to the modified Sharp/van der Heijde (SvH) score. Responsiveness was evaluated according to the European League of Associations for Rheumatology (EULAR) response criteria based on 28 joints. RESULTS: Both S100 proteins were significantly higher in seropositive than in seronegative patients (p = 0.01). Calprotectin correlated significantly with CRP (ρ = 0.51-0.75), ESR (ρ = 0.32-0.52), and DAS28 (ρ = 0.32-0.62). S100A12 correlated with calprotectin (ρ = 0.62-0.77) and CRP (ρ = 0.32-0.63). The S100 proteins, and especially calprotectin (ρ = 0.23-0.39), showed weak associations with radiographic progression, unlike CRP/ESR. None of the S100 proteins could predict responsiveness. CONCLUSIONS: Calprotectin showed the strongest correlation with measures of disease activity and may be better than S100A12 when evaluating disease activity in RA patients. More extensive studies are needed to further compare the predictive value of the S100 proteins relative to radiographic progression.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Calgranulina A/sangre , Calgranulina B/sangre , Infliximab/uso terapéutico , Proteína S100A12/sangre , Adulto , Anciano , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/inmunología , Biomarcadores/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/inmunología , Quimioterapia Combinada , Ensayo de Inmunoadsorción Enzimática , Femenino , Articulaciones del Pie/diagnóstico por imagen , Glucocorticoides/uso terapéutico , Articulaciones de la Mano/diagnóstico por imagen , Humanos , Complejo de Antígeno L1 de Leucocito/sangre , Estudios Longitudinales , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Péptidos Cíclicos/inmunología , Prednisolona/uso terapéutico , Estudios Prospectivos , Radiografía , Factor Reumatoide/inmunología , Índice de Severidad de la Enfermedad , Articulación de la Muñeca/diagnóstico por imagen , Adulto JovenRESUMEN
Primary Sjögren's syndrome (pSS) is a chronic, inflammatory autoimmune disease characterised by lymphocytic infiltrations in the exocrine glands, resulting in destruction of salivary and lacrimal glands. B cells have an important role in the disease, as detection of autoantibodies against SSA/Ro or SSB/La is one of the diagnostic criteria, being found in a majority of the patients. Toll-like receptors (TLR) are pattern recognition receptors. TLR-7 and -9 are found in endosomes and bind microbial nucleic acids. We have previously shown that pSS patients and healthy controls have similar expression pattern of TLR-7 and -9 in various B-cell populations. In this study we further analysed the responsiveness of B cells upon TLR stimulation. B cells isolated from peripheral blood of 21 pSS patients and 18 healthy controls were stimulated with TLR-7 and -9 ligands for 24 h before being analysed for the expression of certain surface markers and intracellular cytokine levels by flow cytometry. Secreted cytokines were measured by a multiplex cytokine assay. Patients with pSS had more naïve and less preswitched memory B cells compared to controls in unstimulated as well as via TLR-7 stimulated cells. Unstimulated and via TLR-7 stimulated B cells from pSS patients also had fewer IL-10(+) preswitched memory B cells. Moreover, TLR-7 and -9 stimulated B cells of pSS patients secreted increased amounts of several cytokines. B cells of pSS patients show a different responsiveness upon stimulation of TLR-7 and -9 compared to controls.
Asunto(s)
Linfocitos B/inmunología , Citocinas/inmunología , Síndrome de Sjögren/inmunología , Receptor Toll-Like 7/inmunología , Receptor Toll-Like 9/inmunología , Adulto , Anciano , Citocinas/sangre , Femenino , Humanos , Activación de Linfocitos/inmunología , Persona de Mediana Edad , Adulto JovenAsunto(s)
Complejo de Antígeno L1 de Leucocito/sangre , Proteínas S100/sangre , Síndrome de Sjögren/sangre , Adulto , Anciano , Fatiga/sangre , Fatiga/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína S100A12 , Glándulas Salivales/fisiopatología , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/fisiopatologíaRESUMEN
The genetic background of primary Sjögren's syndrome (pSS) is partly shared with systemic lupus erythematosus (SLE). Immunoglobulin G Fc receptors are important for clearance of immune complexes. Fcγ receptor variants and gene deletion have been found to confer SLE risk. In this study, four Fcγ receptor single-nucleotide polymorphisms (SNPs) and one copy number variation (CNV) were studied. Swedish and Norwegian pSS patients (N=527) and controls (N=528) were genotyped for the Fcγ receptor gene variant FCGR2A H131R (rs1801274) by the Illumina GoldenGate assay. FCGR3A F158V (rs396991) was analysed in 488 patients and 485 controls, FCGR3B rs447536 was analysed in 471 patients and 467 controls, and FCGR3B rs448740 was analysed in 478 cases and 455 controls, using TaqMan SNP genotyping assays. FCGR3B CNV was analysed in 124 patients and 139 controls using a TaqMan copy number assay. None of the SNPs showed any association with pSS. Also, no FCGR3B CNV association was detected. The lack of association of pSS with Fcγ receptor gene variants indicates that defective immune complex clearance may not be as important in pSS pathogenesis as in SLE, and may point to important differences between SLE and pSS.
Asunto(s)
Receptores de IgG/genética , Síndrome de Sjögren/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Eliminación de Gen , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Noruega , Polimorfismo de Nucleótido Simple , SueciaRESUMEN
Sjögren's syndrome (SS) is a systemic rheumatic autoimmune disease affecting the exocrine glandular function and is characterized by the presence of autoantibodies against the ribonucleoprotein particles, SS-A/Ro and SS-B/La, and mononuclear cell infiltration of exocrine tissues. Our aim is to characterize memory B cell pattern and function in relation to the progression of the disease, by analysing samples from a well-defined cohort of patients with primary SS. We have measured the number of Ro/La-specific plasma cells in peripheral blood mononuclear cells (PBMC) from 23 patients and 20 healthy controls by direct enzyme-linked immunospot (ELISPOT) assay. Furthermore, we quantified the Ro- and La-specific memory B cells in these individuals by a 6-day in vitro polyclonal stimulation of PBMC followed by an antigen-specific ELISPOT assay for the detection of memory B cells. In addition to this, ELISA profiling of autoantibodies was carried out using patients' plasma and supernatant, collected post-mitogen stimulation of PBMC. The average Ro60-, Ro52- and La48-specific plasma cells in PB was 9, 17 and 13 cells in 10(5) PBMC, respectively. After in vitro stimulation, these numbers increased to 43, 50 and 26 for Ro60, Ro52 and La48, correspondingly. However, the fraction of memory B cells activated into antibody-secreting cells was lower than the overall IgG B cell population. We conclude that these lower Ro/La-specific memory B cell levels may indicate that a greater portion of the Ro- and La-specific B cells are in an activated stage. This is in tune with previous reports.
Asunto(s)
Autoanticuerpos/inmunología , Autoantígenos/inmunología , Linfocitos B/inmunología , Memoria Inmunológica/inmunología , Ribonucleoproteínas/inmunología , Síndrome de Sjögren/inmunología , Adulto , Anciano , Autoanticuerpos/sangre , Estudios de Cohortes , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Síndrome de Sjögren/sangre , Antígeno SS-BRESUMEN
OBJECTIVE: Primary Sjögren's syndrome (PSS) is a chronic autoimmune inflammatory disease characterized by exocrine gland inflammation producing clinical symptoms such as dryness of the mouth and eyes. The reported prevalence of PSS is variable, probably because of different classification criteria used and selection bias. The aim of this study was to determine the prevalence of PSS in a well-defined Norwegian Caucasian population using the revised American-European Consensus Group (AECG) criteria. METHODS: Three hospitals and three private rheumatology practices provide all of the rheumatology services to the local population in Hordaland and Rogaland counties, which included 852 342 Caucasian inhabitants as of 1 January 2009. Patients on file fulfilling the new revised AECG criteria for PSS were included, and patients with incomplete data were invited to a screening visit. RESULTS: A total of 424 PSS patients were identified. Their mean age was 61.6 ± 13.2 years; 28 (7%) were men and 396 (93%) were women. The point estimate for the proportion of PSS was 0.050% [95% confidence interval (CI) 0.048-0.052]. CONCLUSION: The prevalence of PSS in this Norwegian population of Caucasians is lower than previously reported when less stringent criteria for identifying PSS were used, but is in line with more recent studies using the same criteria and methods as in this study.
Asunto(s)
Síndrome de Sjögren/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Prevalencia , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/fisiopatologíaRESUMEN
We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10(-5), OR 1.68, the family with sequence similarity 167 member A-B-lymphoid tyrosine kinase (FAM167A-BLK) locus, P=4.7 × 10(-4), OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10(-4), OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.
Asunto(s)
Ligando OX40/genética , Proteínas Tirosina Quinasas/genética , Síndrome de Sjögren/genética , Síndrome de Sjögren/inmunología , Transactivadores/genética , Linfocitos B/inmunología , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Factores Reguladores del Interferón/genética , Interleucina-6/genética , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Noruega , Polimorfismo de Nucleótido Simple , Factor de Transcripción STAT4/genética , Síndrome de Sjögren/enzimología , SueciaRESUMEN
Production of autoantibodies is one of the main features of primary Sjögren's syndrome (pSS). Long-lived plasma cells (PC) can produce autoantibodies for prolonged period of times without being affected by immunosuppressive therapies. As of today, little is known about the long-lived PC subset and their contribution to autoimmunity. We have characterized the phenotypic and migratory properties of peripheral blood PC isolated from pSS patients (grouped by focus score, FS) and compared them to PC from rheumatoid arthritis (RA) patients and normal non-autoimmune subjects. We observed two populations of PC in all study groups, CD19+ PC and CD19- PC. Interestingly, the CD19- PC subset was most prominent in autoimmune patients (pSS and RA) compared to normal controls. Further investigation of the PC phenotype revealed that a high percentage of both CD19+ and CD19- PC isolated from pSS and RA patients did not express the CD27 marker, which is normally highly expressed on all types of PC. Differences in the expression of markers such as IgM, IgG, CD95 and CXCR3 in the group with high FS compared to FS = 1, underscore the heterogeneity of pSS patient group and demonstrate that phenotypic pattern of circulating PC associates with the severity of inflammation in the salivary glands of these patients. Our migration experiments show that addition of CXCL12 to PC in vitro, do not alter the migration potential of PC in any group tested. However, we observed an overall higher spontaneous migration of PC from pSS compared to both RA and normal controls.
Asunto(s)
Artritis Reumatoide/inmunología , Autoanticuerpos/sangre , Células Plasmáticas/inmunología , Síndrome de Sjögren/inmunología , ADP-Ribosil Ciclasa 1/sangre , Antígenos CD19/sangre , Artritis Reumatoide/sangre , Movimiento Celular/inmunología , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Receptores CXCR3/sangre , Receptores CXCR4/sangre , Síndrome de Sjögren/sangre , Sindecano-1/sangreRESUMEN
Primary Sjögren's syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) >1.4 and P-values <0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P=2.5 x 10(-9). The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.
Asunto(s)
Alelos , Factores Reguladores del Interferón/genética , Factor de Transcripción STAT4/genética , Síndrome de Sjögren/genética , Anciano , Pueblo Asiatico/genética , Pueblo Asiatico/estadística & datos numéricos , Estudios de Casos y Controles , Estudios de Cohortes , Intervalos de Confianza , Femenino , Frecuencia de los Genes , Haplotipos , Heterocigoto , Humanos , Factores Reguladores del Interferón/inmunología , Modelos Lineales , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Noruega , Oportunidad Relativa , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Probabilidad , Factores de Riesgo , Factor de Transcripción STAT4/inmunología , Síndrome de Sjögren/inmunología , Suecia , Población Blanca/genética , Población Blanca/estadística & datos numéricosRESUMEN
Vitamin D, besides having well-known control functions of calcium and phosphorus metabolism, bone formation and mineralization, also has a role in the maintenance of immune-homeostasis. The immune-regulatory role of vitamin D affects both the innate and adaptive immune system contributing to the immune-tolerance of self-structures. Impaired vitamin D supply/regulation, amongst other factors, leads to the development of autoimmune processes in animal models of various autoimmune diseases. The administration of vitamin D in these animals leads to improvement of immune-mediated symptoms. Moreover, in human autoimmune diseases, such as multiple sclerosis, or rheumatoid arthritis the pathogenic role of vitamin D has been described. The review aims at describing the complex immune-regulatory role of vitamin D from the cellular level through autoimmune animal models and depicting the known contribution of vitamin D in the pathogenesis of human autoimmune diseases.
Asunto(s)
Enfermedades Autoinmunes/fisiopatología , Deficiencia de Vitamina D/inmunología , Vitamina D/fisiología , Animales , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/dietoterapia , Modelos Animales de Enfermedad , Humanos , Inmunidad Activa , Inmunidad Innata , Ratones , Receptores de Calcitriol/metabolismo , Vitamina D/sangre , Vitamina D/farmacología , Vitamina D/uso terapéuticoRESUMEN
OBJECTIVE: To estimate the point prevalence of primary Sjögren's syndrome (pSS) in two populations, aged 40-44 and 71-74 years, using two sets of classification criteria. METHODS: The participating individuals were recruited from the Hordaland Health Study (HUSK) conducted during 1997-99. A total of 18 592 individuals born 1953-57 and 3346 individuals born 1925-27 were sent a questionnaire covering various health-related questions, including four questions about sicca symptoms. Among those answering positive to at least one of the four questions, 99 and 90 individuals born 1953-57 and 1925-27, respectively, were examined further. For diagnosis of pSS two classifications were used, the preliminary European criteria from 1993, and the revised European criteria from 1996. RESULTS: By using the two classification criteria from 1993 and 1996, the point prevalences were 0.44% [95% confidence interval (CI) 0.34-0.57] and 0.22% (95% CI 0.15-0.32), respectively, for the population group born 1953-57. The corresponding estimates were 3.39% (95% CI 2.77-4.14) and 1.40% (95% CI 1.02-1.92) for the population born 1925-27. CONCLUSION: The point prevalence of pSS was approximately seven times higher in the elderly population aged 71-74 years compared to individuals aged 40-44 years, regardless of the classification criteria used.
Asunto(s)
Síndrome de Sjögren/epidemiología , Anciano de 80 o más Años , Síndromes de Ojo Seco/epidemiología , Europa (Continente) , Humanos , Noruega/epidemiología , Prevalencia , Síndrome de Sjögren/clasificación , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Few studies have addressed the natural course of, or prognostic factors for the salivary and lacrimal function in primary Sjögren syndrome (SS). Except for the early stages, glandular function has been seemingly stable, and SS A antigen (SSA) seropositivity and hypocomplementemia may predict a decline in the van Bijsterveld score. The aim of the present study was to assess the natural course of the exocrine function in a larger cohort based on the American-European consensus criteria for SS, and to address possible predictive factors for a declining exocrine function. METHODS: We performed a retrospective cohort study. A total of 141 patients were investigated with the Schirmer I test and unstimulated whole saliva (UWS). Historical data regarding these tests and focus score were collected from the files of 111 patients. Median time from diagnosis to follow-up investigation was 5.0 years. RESULTS: Median UWS was unchanged during follow-up. Median Schirmer I test improved from 5.0 to 7.0 mm/5 min (p<0.05). Present Schirmer I test was associated with historical high IgG and IgA, positive SSA and SS B antigen (SSB) tests and high focus score, and present UWS with historical low C3/C4. Logistic regression identified high focus scores (odds ratio (OR) = 1.343), and low UWS (OR = 0.692) as factors predicting a 30% or more worsening of the Schirmer I test. High focus scores (OR = 1.488) predicted a 30% or more worsening of the UWS. CONCLUSION: We confirmed previous studies showing a stable or slightly improved exocrine function over time. High focus scores and low UWS were identified as independent predictors of a worsened exocrine function.
Asunto(s)
Aparato Lagrimal/fisiopatología , Glándulas Salivales Menores/fisiopatología , Síndrome de Sjögren/fisiopatología , Anciano , Progresión de la Enfermedad , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
OBJECTIVES: Serum cytokines play an important role in the pathogenesis of psoriatic arthritis (PsA) by initiating and perpetuating various cellular and humoral autoimmune processes. The aim of this study was to describe a broad spectrum of T- and B-cell cytokines, growth factors and chemokines in patients with PsA and healthy individuals. METHODS: A novel protein array system, denoted as multiplex cytokine assay was utilized to measure simultaneously the levels of 23 circulating cytokines of patients with PsA and healthy individuals. Additionally, correlational clustering and discriminant function analysis (DFA), two multivariate, supervised analysis methods were employed to identify a subset of biomarkers in order to describe potential functional inter-relationships among these pathological cytokines and identify biomarkers with prognostic and diagnostic utility. RESULTS: Univariate analysis demonstrated that serum levels of a complex set of immune and inflammatory modulating cytokines are significantly up-regulated in patients with PsA relative to unaffected controls including interleukin (IL)-10, IL-13, interferen (IFN)-alpha, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), fibroblast growth factor [CCL3 macrophage inflammatory protein (MIP)-1alpha], CCL4 (MIP-1beta) and CCL11 (Eotaxin), while granulocyte-colony stimulating factor was significantly reduced in PsA patients. Correlational clustering was able to discriminate among, and hence subclassify, patients with varying levels of disease activity, which may prove useful in guiding therapy in these apparently phenotypically distinct disease subsets. DFA identified EGF, IFN-alpha, VEGF, CCL3 (MIP-1alpha) and IL-12p40 as analytes with the strongest discriminatory power among various PsA patients and controls. CONCLUSIONS: Our findings suggest that these factors modulate PsA pathology and the articular involvement in a synergistic manner. Identifying factors could be used in the development of clinical diagnostic tests, which are valuable to guide evidence-based diagnosis and disease management of PsA.
Asunto(s)
Artritis Psoriásica/inmunología , Citocinas/sangre , Adulto , Anciano , Artritis Psoriásica/patología , Biomarcadores/sangre , Análisis por Conglomerados , Femenino , Humanos , Mediadores de Inflamación/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Análisis por Matrices de Proteínas/métodos , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To investigate the presence of oral bacterial DNAs in serum and synovial fluid (SF) of patients with active rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: Serum and SF samples from 16 RA patients, 14 PsA patients, and 9 osteoarthritis (controls) patients were extracted for oral bacterial DNA. This was used in a checkerboard DNA-DNA-hybridization set up, to identify 40 different bacteria. RESULTS: Mean number +/- standard deviation (SD) of oral bacterial species in sera were 6.2 (3.2) in the RA group (p = 0.004) and 5.4 (2.7) in the PsA group (p = 0.009) compared to 2.1 (1.7) in the controls. Periodontitis associated species Porphyromonas gingivalis and Prevotella nigrescens were exclusively detected in RA and PsA. Mean number (+/- SD) of oral bacterial species in SF were 14.0 (6.8) in the RA (p = 0.001) and 19.4 (7.1) in the PsA group (p < 0.001) compared to 4.0 (1.7) in controls. P. gingivalis, Tannerella forsythensis and Prevotella intermedia were exclusively identified in RA and PsA SF. Higher means of DNAs were found in RA SF compared to RA serum (p < 0.001), and in PsA SF compared to PsA serum (p < 0.001). Higher concentrations of bacterial DNAs were found in RA and PsA compared to controls. CONCLUSION: Higher variety and concentrations of oral bacterial DNAs were found in SF compared to serum of RA and PsA patients. These findings indicate that synovial inflammation in RA and PsA may favor trapping of oral bacterial DNAs, suggesting a perpetuating effect of oral pathogens in joint disease.
Asunto(s)
Artritis Psoriásica/microbiología , Artritis Reumatoide/microbiología , ADN Bacteriano/análisis , Osteoartritis/microbiología , Líquido Sinovial/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Artritis Psoriásica/sangre , Artritis Reumatoide/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hibridación de Ácido Nucleico , Osteoartritis/sangre , Periodontitis/microbiología , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/aislamiento & purificación , Prevotella intermedia/genética , Prevotella intermedia/aislamiento & purificaciónRESUMEN
OBJECTIVE: Calprotectin is a granulocyte and monocyte cytosolic protein that is released during activation of these cells. The plasma level of calprotectin is raised in various inflammatory conditions and correlates with disease activity in a wide range of rheumatic diseases. We wanted to investigate whether calprotectin may be useful as a measure of disease activity in polymyalgia rheumatica (PMR) and temporal arteritis (TA). METHODS: Forty-seven patients with PMR and/or TA were followed up to 3 years in a prospective longitudinal design. Plasma calprotectin was correlated with acute phase parameters, erythrocyte sedimentation rate (ESR), and peroral steroid usage before start of treatment and at four subsequent time intervals. RESULTS: Thirty-three patients had PMR, 10 had TA, and four had both diagnoses. Calprotectin was highly correlated with the acute phase parameters and ESR during the study period. Calprotectin was significantly decreased after start of treatment with oral prednisolone, and correlated with the daily dosage of prednisolone (r = 0.36, p < 0.01). CONCLUSION: Calprotectin plasma levels were significantly associated with acute phase parameters, ESR, and prednisolone usage in PMR and TA, indicating that calprotectin may be a good measure of disease activity in these conditions.
Asunto(s)
Biomarcadores/sangre , Arteritis de Células Gigantes/sangre , Complejo de Antígeno L1 de Leucocito/sangre , Polimialgia Reumática/sangre , Reacción de Fase Aguda/sangre , Anciano , Antiinflamatorios/uso terapéutico , Sedimentación Sanguínea , Femenino , Arteritis de Células Gigantes/diagnóstico , Humanos , Masculino , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamiento farmacológico , Prednisolona/uso terapéutico , Estudios ProspectivosRESUMEN
OBJECTIVES: To study temporomandibular joint (TMJ) involvement, salivary gland dysfunction and oral mucosal lesions in rheumatoid arthritis (RA), and to investigate the relationship to general disease activity. SUBJECTS AND METHODS: The TMJ dysfunction index (D(i)), mean salivary flow and disease activity score (DAS28), were calculated for 50 RA-patients, and 23 non-RA patients (controls). RESULTS: Median D(i) was 5.5 (range: 0-21) for the RA-patients compared with 2.0 (range: 0-9) for the controls (P < 0.0001). Pain on movement of the TMJ (P = 0.015), muscular pain (P = 0.006), TMJ pain (P = 0.019) and D(i) as a total (P = 0.009), significantly correlated with DAS28. Mean resting whole saliva (RWS) flow was 2.6 (s.d. 2.4) ml per 15 min for the RA-patients and 4.5 (s.d. 3.0) for the controls (P = 0.003). RWS correlated positively with haemoglobin (P = 0.021) and negatively with Westergren erythrocyte sedimentation rate (ESR) (P = 0.029). No major differences in frequency of oral mucosal lesions were seen between RA-patients and controls. CONCLUSIONS: Higher frequency of TMJ and salivary gland dysfunction in RA-patients compared with controls has been demonstrated. RA disease activity is associated with hyposalivation and TMJ dysfunction.
Asunto(s)
Artritis Reumatoide/complicaciones , Enfermedades de las Glándulas Salivales/etiología , Trastornos de la Articulación Temporomandibular/etiología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Boca/etiología , Enfermedades de la Boca/fisiopatología , Mucosa Bucal , Enfermedades de las Glándulas Salivales/fisiopatología , Estadísticas no Paramétricas , Trastornos de la Articulación Temporomandibular/fisiopatología , Xerostomía/etiologíaRESUMEN
BACKGROUND: Rheumatic joint pain is a common extra-intestinal complication of inflammatory bowel disease (IBD). Because the high ratio of n-6 to n-3 fatty acids (FAs) of the Western diet might promote rheumatic disorders, we sought to compare the effects of short-term duodenal administration of n-3-rich seal oil and n-6-rich soy oil on IBD-related joint pain. METHODS: Nineteen patients with IBD-related joint pain were included in the study; 9 had Crohn disease and 10 had ulcerative colitis. Ten millilitres seal oil (n = 10) or soy oil (n = 9) was self-administered through a nasoduodenal feeding tube 3 times daily for 10 days. RESULTS: Compared with soy oil treatment, seal oil significantly reduced the duration of morning stiffness (P = 0.024), number of tender joints (P = 0.035), intensity of pain (P = 0.025) and the doctor's scoring of rheumatic disease activity (P = 0.025) at the end of the 10-day treatment period. Analysis of the effects as area under the curve (area between the curve and baseline, zero) for the entire period from start of treatment until 6 months' post-treatment suggested a long-lasting beneficial effect of seal oil administration on joint pain, whereas soy oil tended (not significantly) to aggravate the condition. Consistently, the serum ratios of n-6 to n-3 FAs (P < 0.01) and arachidonic acid to eicosapentaenoic acid (P < 0.01) were reduced after treatment with seal oil. CONCLUSION: The results suggest distinctive, differential prolonged effects on IBD-related joint pain of short-term duodenal administration of n-3-rich seal oil (significant improvement) and n-6-rich soy oil (tendency to exacerbation).
Asunto(s)
Artralgia/terapia , Ácidos Grasos Omega-3/administración & dosificación , Enfermedades Inflamatorias del Intestino/complicaciones , Aceite de Soja/administración & dosificación , Adolescente , Adulto , Animales , Artralgia/sangre , Artralgia/etiología , Duodeno , Ácidos Grasos/sangre , Ácidos Grasos Omega-6/administración & dosificación , Femenino , Lobos Marinos , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Intubación Gastrointestinal , Masculino , Persona de Mediana EdadRESUMEN
Plasma cytokines play an important role in the pathogenesis of Sjögren's syndrome (SS) by initiating and perpetuating various cellular and humoural autoimmune processes. The aim of the present study was to describe a broad spectrum of T-cell and B-cell cytokines, growth factors, chemokines and molecules that could contribute to cell death in SS. A novel protein array system was utilized to measure simultaneously the levels of 25 plasma cytokines of patients with primary SS and healthy individuals. Furthermore, we correlated these plasma cytokine levels with potential laboratory and clinical parameters related to disease activity in SS. A subset of plasma cytokines [e.g. interleukin-1beta (IL-1beta), IL-6, CXCL8 (IL-8), IL-12 p40, IL-15, tumour necrosis factor-alpha (TNF-alpha), epidermal growth factor, CCL4 (MIP-1beta), CCL2 (MCP-1), CCL11 (Eotaxin), CCL5 (RANTES), TNF-RI and TNF-RII] was found to significantly differ between patients and controls. Also, distinct populations of cytokines were found to differentiate between patients with normal versus elevated ESR or IgG levels and patients with the presence or absence of extra-glandular manifestations (EGMs). Our results support the assumption that the multiplex cytokine array system can be successfully utilized in the diagnosis and disease management of SS. Furthermore, it may provide a powerful tool in the design of individualized anticytokine therapies.
Asunto(s)
Citocinas/sangre , Síndrome de Sjögren/sangre , Síndrome de Sjögren/patología , Adulto , Anciano , Anciano de 80 o más Años , Sedimentación Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis por Matrices de ProteínasRESUMEN
OBJECTIVES: To investigate whether out-patients with a clinical diagnosis of Sjögren's syndrome (SS) satisfied current preliminary European criteria for SS, and to determine the proportion of patients who satisfied the proposed modified European criteria for SS and thus had indication of an autoimmune process. METHODS: Out-patients with a clinical diagnosis of SS registered between 1 January 1999 and 1 November 2000 were included in the study. RESULTS: Of 203 patients with a clinical diagnosis of SS, 116 (57.1%) satisfied the current European criteria and 83 (40.9%) satisfied the proposed modified criteria. CONCLUSIONS: Sicca symptoms and signs may have a variety of causes. In our study only 40.9% of the patients with a clinical diagnosis of SS satisfied the proposed modified European criteria and had evidence of SS as an autoimmune condition. Our findings indicate that for patient populations with an established diagnosis of SS according to the preliminary European criteria, approximately one-third will lose the diagnosis according to the modified criteria.