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1.
Eur Arch Otorhinolaryngol ; 277(6): 1675-1680, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32128609

RESUMO

PURPOSE: Research indicates that rheumatic disorders are accompanied by decreased chemosensory function. The present study aimed to specifically evaluate this issue in patients with rheumatoid arthritis (RA). METHODS: 212 RA patients (43 men, 169 women, mean age 59 ± 13.3 years), and 30 healthy controls (10 men, 20 women, mean age 40 ± 15.3 years), were included in this study. Chemosensory measurements consisted of olfactory testing using the "Sniffin' Sticks" test battery (with odor thresholds, odor discrimination and odor identification; OT, OD, OI) and gustatory testing on a suprathreshold and a quasi-threshold level using "taste sprays" and "taste strips", respectively. In addition, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) and RA autoantibodies (anti-cyclic citrullinated peptides, RA factors) were evaluated. RESULTS: Olfactory measurements showed 4% of the RA patients functionally anosmic and 40% hyposmic. RA patients scored significantly lower in suprathreshold olfactory tests (OD, OI) compared to controls (OI: 12.5 ± 2.5 vs. 14.1 ± 1.3; OD: 11.3 ± 2.7 vs. 12.9 ± 1.7). In addition, RA patient had decreased taste function compared to healthy individuals (10.4 ± 2.6 vs. 11.7 ± 1.7). Chemosensory function did not correlate with parameters related to the severity of disease. CONCLUSION: Chemosensory function (taste, OD and OI) appears to be decreased in RA patients. In contrast, OT was not affected. Changes in chemosensory function seem to be independent of disease parameters such as duration of disease or disease activity.

2.
PLoS One ; 14(5): e0217412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31136632

RESUMO

OBJECTIVES: To investigate the prevalence of depressive symptoms in rheumatoid arthritis (RA) patients using two previously validated questionnaires in a large patient sample, and to evaluate depressive symptoms in the context of clinical characteristics (e.g. remission of disease) and patient-reported impact of disease. METHODS: In this cross-sectional study, the previously validated Patient Health Questionnaire (PHQ-9) and Beck-Depression Inventory II (BDI-II) were used to assess the extent of depressive symptoms in RA patients. Demographic background, RA disease activity score (DAS28), RA impact of disease (RAID) score, comorbidities, anti-rheumatic therapy and antidepressive treatment, were recorded. Cut-off values for depressive symptomatology were PHQ-9 ≥5 or BDI-II ≥14 for mild depressive symptoms or worse and PHQ-9 ≥ 10 or BDI-II ≥ 20 for moderate depressive symptoms or worse. Prevalence of depressive symptomatology was derived by frequency analysis while factors independently associated with depressive symptomatology were investigated by using multiple logistic regression analyses. Ethics committee approval was obtained, and all patients provided written informed consent before participation. RESULTS: In 1004 RA-patients (75.1% female, mean±SD age: 61.0±12.9 years, mean disease duration: 12.2±9.9 years, DAS28 (ESR): 2.5±1.2), the prevalence of depressive symptoms was 55.4% (mild or worse) and 22.8% (moderate or worse). Characteristics independently associated with depressive symptomatology were: age <60 years (OR = 1.78), RAID score >2 (OR = 10.54) and presence of chronic pain (OR = 3.25). Of patients classified as having depressive symptoms, only 11.7% were receiving anti-depressive therapy. CONCLUSIONS: Mild and moderate depressive symptoms were common in RA patients according to validated tools. In routine clinical practice, screening for depression with corresponding follow-up procedures is as relevant as incorporating these results with patient-reported outcomes (e.g. symptom state), because the mere assessment of clinical disease activity does not sufficiently reflect the prevalence of depressive symptoms. CLINICAL TRIAL REGISTRATION NUMBER: This study is registered in the Deutsches Register Klinischer Studien (DRKS00003231) and ClinicalTrials.gov (NCT02485483).


Assuntos
Artrite Reumatoide/psicologia , Depressão/epidemiologia , Idoso , Artrite Reumatoide/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários
3.
J Rheumatol ; 46(5): 460-466, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30504510

RESUMO

OBJECTIVE: To analyze the effect of a risk-stratified disease-modifying antirheumatic drug (DMARD)-tapering algorithm based on multibiomarker disease activity (MBDA) score and anticitrullinated protein antibodies (ACPA) on direct treatment costs for patients with rheumatoid arthritis (RA) in sustained remission. METHODS: The study was a posthoc retrospective analysis of direct treatment costs for 146 patients with RA in sustained remission tapering and stopping DMARD treatment, in the prospective randomized RETRO study. MBDA scores and ACPA status were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and direct treatment costs were evaluated every 3 months. MBDA and ACPA status were used as predictors creating a risk-stratified tapering algorithm based on relapse rates. RESULTS: RA patients with a low MBDA score (< 30 units) and negative ACPA showed the lowest relapse risk (19%), while double-positive patients showed high relapse risk (61%). In ACPA-negative and MBDA-negative (< 30 units), and ACPA or MBDA single-positive (> 30 units) groups, DMARD tapering appears feasible. Considering only patients without flare, direct costs for synthetic and biologic DMARD in the ACPA/MBDA-negative and single positive groups (n = 41) would have been €372,245.16 for full-dose treatment over 1 year. Tapering and stopping DMARD in this low-risk relapse group allowed a reduction of €219,712.03 of DMARD costs. Average reduction of DMARD costs per patient was €5358.83. CONCLUSION: Combining MBDA score and ACPA status at baseline may allow risk stratification for successful DMARD tapering and cost-effective use of biologic DMARD in patients in deep remission as defined by the 28-joint count Disease Activity Score using erythrocyte sedimentation rate.


Assuntos
Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Autoanticorpos/análise , Análise Custo-Benefício , Adulto , Algoritmos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Biomarcadores/análise , Estudos de Coortes , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença
4.
Ultrasound Int Open ; 4(2): E61-E68, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30182091

RESUMO

Background: The detection of joint swelling caused by synovitis is important for the diagnosis of inflammatory arthritis. Ultrasound (US) and MRI have proven to be more sensitive and reliable than physical examination, but they are time-consuming and expensive. The automated breast volume scanner was developed to acquire serial B-mode pictures of the female breast and these can be analyzed in all three dimensions. Objectives: To analyze the value of automated B-mode ultrasound employing the ABVS system in detecting synovitis of the finger joints compared to manual ultrasound (mUS) and physical examination, using MRI as the gold standard. Methods: 19 consecutive patients suffering from active rheumatoid (n=15) or psoriatic (n=4) arthritis were included. Automated and mUS were conducted with a linear array (ACUSON S2000™, 11 MHz). Multiplanar reconstruction enabled examination of the images for the presence of synovitis. Results: 90% of the hand joints were assessable by automated ultrasound. Automated US detected 12.0, mUS 14.2, MRI 13.4, and clinical examination 4.1 positive joints - i. e. joints with synovitis - on average per patient. The inter-observer reliability of both assessors for automated and mUS, MRI, and physical examination, was 66.9%, 72.7%, 95.1%, and 88.9%, respectively. 84.3% of the joints classified as positive on MRI were confirmed by automated ultrasound, 85.5% on mUS, and 36.0 on physical examination. This translated into a sensitivity of 83.5%, 85.5%, and 36.0% for the three methods, respectively. Conclusion: Automated ultrasound is a promising ultrasound method for assessing small joints in patients with inflammatory arthritis.

5.
Int J Psychophysiol ; 86(2): 182-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22985737

RESUMO

BACKGROUND: Self-reports of fibromyalgia (FM) patients about an enhanced olfactory acuity have been used to characterize them as persons with a general increased sensitivity to sensory input consistent with a central sensitization. However, as reduced activations in some brain areas also seem to accompany FM, a multisensory hypersensitivity is not a necessary consequence. METHODS: FM patients meeting ARA (American Rheumatism Association) criteria (16 women and one man, aged 23-56 years, spontaneous pain 32-91 mm visual analog scale [VAS], 14-18 tender points with a pressure pain threshold of 1.5±0.7 kg/cm(2)) received an olfactory test (Sniffn' Sticks) to assess their odor thresholds to n-butanol and their ability to discriminate and identify odors. Healthy controls were 14 age-matched women and one man. RESULTS: Patients had poorer odor identification than controls (14.6±1.3 vs. 15.5±0.6; p<0.05) but did not differ in odor thresholds or odor discrimination. This test result contrasted with the patients' self-ratings of their olfactory sensitivity as higher than average. CONCLUSIONS: The perception of FM patients as being multisensory hypersensitive is not supported by present results. In contrast to the subjects' self-ratings, measurements of olfactory function showed a slightly reduced odor identification, with a by-and-large normal performance.


Assuntos
Fibromialgia/epidemiologia , Fibromialgia/fisiopatologia , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/fisiopatologia , Autorrelato , Olfato/fisiologia , Adulto , Feminino , Fibromialgia/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Odorantes , Transtornos do Olfato/diagnóstico , Limiar Sensorial/fisiologia , Adulto Jovem
6.
Ann Rheum Dis ; 69(5): 876-8, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19439430

RESUMO

INTRODUCTION: Psoriasis susceptibility locus 4 (PSORS4) is a susceptibility locus for psoriasis vulgaris (PsV), a common inflammatory, hyperproliferative skin disorder. Recently, a deletion of 2 late cornified envelope (LCE) genes within epidermal differentiation complex on chromosome 1 was shown to be enriched in 1426 patients with PsV, suggesting compromised barrier function in deletion carriers. This genetic association was subsequently confirmed in a German cohort. METHODS: In order to investigate whether this variant also predisposes to psoriatic arthritis (PsA), this deletion and 3 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium with it were genotyped in a case-control cohort of 650 patients and 937 control individuals of German origin. RESULTS: LCE deletion frequency did not significantly differ between patients with PsA and controls (65.0% vs 65.5%). Similarly, no evidence for association to the three SNPs was observed. DISCUSSION: This is the first non-human leucocyte antigen (HLA) risk factor predisposing only to skin type of psoriasis, supporting the concept of partially overlapping but different aetiological factors underlying skin and joint manifestations.


Assuntos
Artrite Psoriásica/genética , Proteínas Ricas em Prolina do Estrato Córneo/genética , Deleção de Genes , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Alemanha , Humanos , Desequilíbrio de Ligação , Masculino , Adulto Jovem
7.
J Invest Dermatol ; 129(2): 355-8, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18800148

RESUMO

Variants in two genes of the IL-23 receptor (R) pathway have recently been shown to be associated with psoriasis vulgaris (PV). We were interested whether the risk conferred by these variants differs between psoriatic skin and joint disease. Four variants of the IL12B and IL23R genes were analyzed in 1,114 PV patients, 748 patients with psoriatic arthritis (PA) and 937 healthy controls before and after stratification for the major psoriasis risk allele at psoriasis susceptibility locus 1 (PSORS1). For both PA and PV, we detected the strongest association with two IL12B single-nucleotide polymorphisms and the corresponding haplotype as reflected by minimal P-values of 10(-7) and highest odds ratios of 1.50 (1.28-1.75) for rs6887695 in PA patients and 1.50 (1.27-1.76) for rs3212227 in the PV cohort, respectively. For IL23R, only rs11209026 showed an association. The results remained significant after correction for multiple testing. No difference was observed after stratification for the PSORS1 risk allele. While confirming recent reports on variants of the IL-23R pathway as susceptibility factors for PV, our study is the first to extend analysis of both genes to PA. However, our results indicate that these variants are not specific risk factors for arthritis, but relevant for susceptibility to psoriasis in general.


Assuntos
Artrite Psoriásica/epidemiologia , Artrite Psoriásica/genética , Variação Genética , Subunidade p40 da Interleucina-12/genética , Receptores de Interleucina/genética , Adolescente , Adulto , Feminino , Frequência do Gene , Predisposição Genética para Doença/epidemiologia , Haplótipos , Humanos , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Psoríase/epidemiologia , Psoríase/genética , Psoríase/metabolismo , Fatores de Risco , Adulto Jovem
8.
Arthritis Rheum ; 56(6): 2056-64, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17530646

RESUMO

OBJECTIVE: Single-nucleotide polymorphisms (SNPs) of the tumor necrosis factor gene TNF at positions -238 and -308 have been associated with psoriasis vulgaris and psoriatic arthritis (PsA). The strong linkage disequilibrium (LD) at chromosome region 6p21, a region known to harbor risk factors for psoriasis susceptibility (PSORS1) other than just SNPs of the TNF gene, renders the interpretation of these findings difficult. The aim of this study was to analyze several SNPs of the TNF gene and its neighboring LTA gene for independent and dependent carriage of the PSORS1 risk allele. METHODS: SNPs in the promoter of the TNF (-238G/A, -308G/A, -857C/T, and -1031T/C), LTA (+252A/G), TNLFRSF1A (+36A/G), and TNLFRSF1B (+676T/G) genes were genotyped in 375 psoriasis patients, 375 PsA patients, and 376 controls. The Trp- Trp-Cys-Cys haplotype of the CCHCR1 gene (CCHCR1*WWCC) was used as an estimate of the risk allele PSORS1. RESULTS: Whereas we were able to confirm the previously described strong association of allele TNF*-238A with psoriasis, our study revealed that this association was completely dependent on carriage of the PSORS1 risk allele. For PsA, but not psoriasis vulgaris without joint involvement, a strong association with the allele TNF*-857T (odds ratio 1.956 [95% confidence interval 1.334-2.881]; corrected P = 0.0025) was also detected in patients negative for the PSORS1 risk allele. CONCLUSION: Our results indicate that there are genetic differences between psoriasis vulgaris patients with and without joint manifestations. While the previously reported association between TNF*-238A and psoriasis seems to primarily reflect LD with PSORS1, TNF*-857T may represent a risk factor for PsA that is independent of the PSORS1 allele.


Assuntos
Artrite Psoriásica/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Estudos de Casos e Controles , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação/genética , Pessoa de Meia-Idade , Fatores de Risco
9.
J Invest Dermatol ; 127(6): 1367-70, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17255953

RESUMO

Psoriasis vulgaris and atopic dermatitis share a number of features such as chronic cutaneous inflammation and disturbed epidermal barrier function. Genome-wide scans have revealed a conspicuous overlap of susceptibility loci for both diseases involving chromosomal regions 1q21, 3q21, 17q25, and 20p12. Recently, two loss-of-function variants in the gene encoding filaggrin at 1q21 were shown to be strongly associated with atopic dermatitis. In view of a possible genetic overlap of the two skin diseases, we investigated 375 patients suffering from psoriasis vulgaris, 375 patients with psoriatic arthritis, and 376 control probands. Moreover we directly studied expression of filaggrin in 10 patients suffering from psoriasis vulgaris. Our immunohistochemical analysis revealed a checkered pattern with alternating positive broadened or almost absent filaggrin expression. However, no association was found for the two variants of filaggrin (FLG). We conclude that despite a markedly altered filaggrin expression in psoriatic skin, loss-of-function variants of the FLG gene are neither associated with psoriasis vulgaris nor with psoriatic arthritis. The abnormal staining might reflect the altered epidermal differentiation. Our findings imply that the genetic background underlying the epidermal barrier defect in psoriasis is distinct from that found in atopic dermatitis.


Assuntos
Artrite Psoriásica/genética , Proteínas de Filamentos Intermediários/genética , Psoríase/genética , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/patologia , Epiderme/metabolismo , Epiderme/patologia , Frequência do Gene , Predisposição Genética para Doença/epidemiologia , Variação Genética , Alemanha/epidemiologia , Humanos , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/metabolismo , Mutação , Psoríase/epidemiologia , Psoríase/patologia , Fatores de Risco
11.
Arthritis Rheum ; 54(5): 1491-500, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16646030

RESUMO

OBJECTIVE: To examine whether single-nucleotide polymorphisms (SNPs) of the interleukin-4 receptor gene IL4R influence susceptibility to, or radiographic progression in, rheumatoid arthritis (RA). METHODS: The contribution of 2 SNPs (I50V and Q551R) in the coding region of IL4R to RA susceptibility was analyzed by allele-specific polymerase chain reaction in a case-control study of 471 RA patients and 371 healthy controls. Patients with available radiographs of the hands and feet obtained 2 years after disease onset (n = 302) were stratified retrospectively according to radiologic outcome into an erosive and a nonerosive group to evaluate the association between IL4R SNPs and disease progression. RESULTS: No differences in the genotype and allele frequencies of the I50V or Q551R SNPs were identified between the RA patients and healthy controls. In contrast, significant differences in the distribution of I50V IL4R SNP genotypes between patients with erosive and nonerosive disease were observed (chi2 = 15.68, P = 0.0004). Bone erosions at 2 years after disease onset were present in 68.1% of patients homozygous for the V50 allele compared with 37.0% of patients homozygous for the I50 allele (odds ratio 3.86, P < 0.0001). This association was independent of individual factors previously associated with severe disease, such as rheumatoid factor or the HLA-DR shared epitope. On a cellular level, the V50 allele conferred significantly reduced responsiveness to interleukin-4, providing a possible mechanism for the association of the I50V IL4R polymorphism with early erosions in RA. CONCLUSION: Our data identify the I50V IL4R SNP as a novel genetic marker in RA, showing high predictive value for early joint destruction.


Assuntos
Artrite Reumatoide/genética , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-4/genética , Artrite Reumatoide/patologia , Progressão da Doença , Feminino , Humanos , Subunidade alfa de Receptor de Interleucina-4 , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
13.
Arthritis Rheum ; 52(2): 451-60, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15692975

RESUMO

OBJECTIVE: Tumor necrosis factor (TNF)-neutralizing agents are the most successful means of ameliorating systemic autoimmune inflammation. Neutralization of TNF, however, is often associated with the development of autoantibodies, particularly to nuclear antigens, and the mechanisms of this are unknown. We undertook this study to analyze the effect of TNF and its neutralization on the expression of major histocompatibility complex class II molecules and on the function of antigen-presenting myeloid cells in rheumatoid arthritis (RA). METHODS: Monocytes were isolated from the peripheral blood of RA patients before and after anti-TNF monoclonal antibody (mAb) treatment and from the peripheral blood of controls by negative selection, differentiated in vitro to macrophages, and analyzed by flow cytometry for HLA-DR expression. T cell responses to activation by myeloid cells were assessed in proliferation assays, and messenger RNA (mRNA) levels of the class II transactivator (CIITA) were determined by semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: HLA-DR expression was significantly reduced on myeloid cells from RA patients with active disease, but was increased to normal levels after anti-TNF mAb treatment. Concordantly, in vitro application of TNF to monocytes from healthy individuals reduced their ability to up-regulate HLA-DR during differentiation to macrophages and, importantly, inhibited their ability to stimulate T cells in mixed lymphocyte reactions. Molecular analysis revealed that the effect of TNF on HLA-DR expression was mediated via suppression of the transcription factor CIITA. CONCLUSION: The data indicate that TNF decreases HLA-DR expression by reducing CIITA mRNA levels in myeloid cells, functionally resulting in a decreased capacity of myeloid cells to stimulate T cells. Concordantly, ameliorating disease activity in chronic inflammatory diseases by neutralizing TNF restores expression of HLA-DR on myeloid cells as well as the ability of myeloid cells to stimulate T cells. Thus, anti-TNF treatment might lead to augmented T cell activation by myeloid cells, thereby promoting immune responses to (auto)antigens and the development of antinuclear antibodies that are frequently associated with anti-TNF therapy.


Assuntos
Células Apresentadoras de Antígenos/fisiologia , Artrite Reumatoide/imunologia , Expressão Gênica , Genes MHC da Classe II/genética , Células Mieloides/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Adulto , Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos , Teste de Cultura Mista de Linfócitos , Pessoa de Meia-Idade , Proteínas Nucleares/análise , Proteínas Nucleares/genética , RNA Mensageiro/análise , Linfócitos T/imunologia , Transativadores/análise , Transativadores/genética , Fator de Necrose Tumoral alfa/imunologia , Regulação para Cima
14.
J Invest Dermatol ; 124(1): 107-10, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15654961

RESUMO

A DNA variant, rs734232, altering a RUNX1 binding site was recently reported as susceptibility allele at PSORS2 (17q25) in cohorts of psoriasis patients from the US. A testing of this variant in psoriasis patients from Germany did not confirm this association in 300 trios nor in two case-control studies with 281 patients with psoriasis vulgaris and 375 patients with psoriatic arthritis, respectively. These results fail to support rs734232 as a psoriasis susceptibility factor in German psoriasis patients.


Assuntos
Artrite Psoriásica/genética , Cromossomos Humanos Par 17 , Proteínas de Ligação a DNA/genética , Proteínas Proto-Oncogênicas/genética , Psoríase/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Artrite Psoriásica/epidemiologia , Sítios de Ligação/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 6 , Estudos de Coortes , Subunidade alfa 2 de Fator de Ligação ao Core , Frequência do Gene , Alemanha/epidemiologia , Haplótipos , Humanos , Pessoa de Meia-Idade , Psoríase/epidemiologia , Fatores de Risco
15.
Eur J Immunol ; 32(5): 1253-63, 2002 05.
Artigo em Inglês | MEDLINE | ID: mdl-11981812

RESUMO

Pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) is unresolved. Dysregulation of programmed cell death is discussed as a pathogenetic factor. We have previously shown that increased in vitro apoptosis of cultured peripheral blood mononuclear cells (PBMC) is nonspecific for SLE. Importantly, however, in recent experiments with SLE PBMC from patients with infections and fever in vitro apoptosis was strongly accelerated. We therefore hypothesized that regulation of apoptosis might be disturbed in activated SLE lymphocytes. Thus, we generated phytohemagglutinine (PHA)/IL-2 stimulated lymphoblasts in vitro. These lymphoblasts readily undergo apoptosis after culture in cytokine-free medium, and can be rescued by addition of gammac-chain cytokines IL-2, -4, -7, or -15. In lymphoblasts from 60 SLE patients tested in comparison to lymphoblasts from normal donors cultured in parallel, we found significant hyporesponsiveness to gammac-chain cytokines in SLE cells. Minor differences were also seen in lymphoblasts from patients with other systemic autoimmunopathies (mixed connective tissue disease, vasculitis, n=49)and in lymphoblasts from patients with other autoimmune diseases (mainly rheumatoid or reactive arthritis, myositis, n=44). In patients with high erythrocyte sedimentation rate (> 25 mm/h), TNF-alpha (> 6.5 pg/ml) or IL-12 (> 4.7 pg/ml) serum levels or detectable IFN-gamma concentrations hyporesponsiveness to gammac-chain cytokines was even more pronounced in SLE lymphoblasts, but not in lymphoblasts from the other groups. Moreover, increased apoptosis was seen in lymphoblasts from SLE patients with decreased complement (C)4 or elevated dsDNA antibody levels. In conclusion, these data suggest that in SLE patients with increased inflammatory activity and/or Th1 dominance signaling through gammac-chain cytokine receptors is deteriorated, leading to facilitated apoptosis of activated lymphocytes and enlarged onflow of apoptotic material.


Assuntos
Apoptose/efeitos dos fármacos , Citocinas/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Adulto , Idoso , Apoptose/imunologia , Estudos de Casos e Controles , Humanos , Técnicas In Vitro , Infecções/imunologia , Infecções/patologia , Interleucinas/farmacologia , Ativação Linfocitária , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/patologia , Linfócitos/patologia , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/imunologia , Doença Mista do Tecido Conjuntivo/patologia , Transdução de Sinais , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/patologia , Vasculite/imunologia , Vasculite/patologia
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