bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal HLA class II compatibility in men with systemic lupus erythematosus
Authors: Stevens Anne M. , Tsao Betty P. , Hahn Bevra H. , Guthrie Katherine , Lambert Nathalie C. , Porter Allison J. , Tylee Tracy S. , Nelson J. Lee 
Published: September 2005

AbstractObjectiveMaternal–fetal cell transfer during pregnancy can lead to long‐lasting microchimerism, which raises the question of whether microchimerism sometimes contributes to autoimmune disease later in life. In an experimental model, transfusion of parental lymphocytes homozygous for major histocompatibility complex alleles results in systemic lupus erythematosus (SLE). We identified male patients with SLE and healthy male subjects and their mothers in order to investigate the mother–son HLA relationship in SLE risk. Male subjects were selected in order to avoid confounding due to fetal microchimerism, which may occur in women.MethodsHLA genotyping for DRB1, DQA1, and DQB1 was conducted for sons and their mothers. Thirty men with SLE and their mothers were compared with 76 healthy men and their mothers.ResultsSons with SLE were HLA‐identical with their mothers (bidirectionally compatible) for the basic HLA–DRB1 groups encoded by DRB1*01 through DRB1*14 more often than were healthy sons (odds ratio [OR] 5.0, P = 0.006). Each DRB1 group contains multiple allelic variants; male patients with SLE and their mothers often were identical for both DRB1 allelic variants (OR 3.2, P = 0.08). For DQA1 and DQB1, the ORs were 2.3 (P = 0.08) and 2.0 (P = 0.21), respectively. When analysis was limited to male subjects with SLE‐associated HLA genes (encoding HLA–DR2 or HLA–DR3), the differences further increased for DRB1 basic groups (OR 7.2, P = 0.01), DRB1 alleles (OR 15.0, P = 0.018), DQA1 6.4 (P = 0.006), and DQB1 (OR 5.7, P = 0.027). No increase in (unidirectional) compatibility of the mother from the son's perspective was observed at any locus.ConclusionWe observed increased bidirectional HLA class II compatibility of male SLE patients and their mothers compared with healthy men and their mothers. This observation implies that maternal microchimerism could sometimes be involved in SLE and therefore merits further investigation.
Is the disease course of rheumatoid arthritis becoming milder?: Time trends since 1985 in an inception cohort of early rheumatoid arthritis
Authors: Welsing Paco M. J. , Fransen Jaap , van Riel Piet L. C. M. 
Published: September 2005

AbstractObjectiveBased on comparisons of short‐term cohort studies or cross‐sectional samples of patients from different calendar times, it has been suggested that present patients with rheumatoid arthritis (RA) have a milder disease course compared with that of patients in past decades. This study was undertaken to investigate whether the course of disease activity and functional disability in patients with RA has become milder over the past several years.MethodsWe used the Nijmegen inception cohort of early RA, which included all patients with newly diagnosed RA who had attended the department of rheumatology at Radboud University Nijmegen Medical Centre since 1985. Patients were assessed for disease activity by the Disease Activity Score in 28 joints (DAS28) every 3 months and for functional disability by the Health Assessment Questionnaire (HAQ) disability index (DI) every 6 months. Within the total cohort, 4 subcohorts were defined, based on the date of inclusion of the patients (1985–1990, 1990–1995, 1995–2000, 2000–2005). To investigate whether the course of disease activity and functional disability (over time) was different between the subcohorts, longitudinal regression analysis (linear mixed models) was used, with the DAS28 and HAQ DI over time as outcome variables, respectively, and subcohort as the independent variable, correcting for baseline demographic and clinical characteristics. The treatment strategy was compared between the subcohorts.ResultsThe DAS28 at baseline and over the first 5 years of disease was lower in the more recent subcohorts. The HAQ DI did not show improvement but instead a trend toward worsening functional disability. Using longitudinal regression it was shown that disease activity improved early in the disease course and stabilized thereafter, and that this improvement was greater in patients in the more recent subcohorts and in patients with a higher baseline DAS28. Initially, the HAQ DI also improved but stabilized thereafter, and this initial improvement was less pronounced in patients in the more recent subcohorts and was greater for patients with a higher baseline HAQ DI. The treatment strategy was more aggressive in the more recent subcohorts, as shown by a shorter duration from diagnosis to the start of treatment with prednisone or disease‐modifying antirheumatic drugs (DMARDs), and a greater prevalence of DMARD therapy.ConclusionThe course of disease activity in RA patients has become milder in more recent years. The reason for this improving trend remains to be elucidated, although the trend coincides with a more aggressive treatment strategy.
Rituximab treatment in patients with primary Sjögren's syndrome: An open‐label phase II study
Authors: Pijpe J. , van Imhoff G. W. , Spijkervet F. K. L. , Roodenburg J. L. N. , Wolbink G. J. , Mansour K. , Vissink A. , Kallenberg C. G. M. , Bootsma H. 
Published: September 2005

AbstractObjectiveTo investigate the safety and efficacy of B cell depletion treatment of patients with active primary Sjögren's syndrome of short duration (early primary SS) and patients with primary SS and mucosa‐associated lymphoid tissue (MALT)–type lymphoma (MALT/primary SS).MethodsFifteen patients with primary SS were included in this phase II trial. Inclusion criteria for the early primary SS group were B cell hyperactivity (IgG >15 gm/liter), presence of autoantibodies (IgM rheumatoid factor, anti‐SSA/SSB), and short disease duration (<4 years). Inclusion criteria for the MALT/primary SS group were primary SS and an associated MALT‐type lymphoma (Ann Arbor stage IE) localized in the parotid gland. Patients were treated with 4 infusions of rituximab (375 mg/m2) given weekly after pretreatment with prednisone (25 mg) and clemastine. Patients were evaluated, using immunologic, salivary/lacrimal function, and subjective parameters, at baseline and at 5 and 12 weeks after the first infusion.ResultsSignificant improvement of subjective symptoms and an increase in salivary gland function was observed in patients with residual salivary gland function. Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. Human antichimeric antibodies (HACAs) developed in 4 of 15 patients (27%), all with early primary SS. Three of these patients developed a serum sickness–like disorder. Of the 7 patients with MALT/primary SS, complete remission was achieved in 3, and disease was stable in 3 and progressive in 1.ConclusionFindings of this phase II study suggest that rituximab is effective in the treatment of primary SS. The high incidence of HACAs and associated side effects observed in this study needs further evaluation.
Prevalence of Barrett's esophagus in systemic sclerosis
Authors: Wipff J. , Allanore Y. , Soussi F. , Terris B. , Abitbol V. , Raymond J. , Chaussade S. , Kahan A. 
Published: September 2005

AbstractObjectiveThe esophagus is the most commonly affected gastrointestinal area in systemic sclerosis (SSc). Patients with SSc frequently develop gastroesophageal reflux, esophageal injury, and sometimes, intestinal metaplasia, or Barrett's esophagus (BE), which may increase the risk of esophageal adenocarcinoma. This study sought to determine the prevalence of BE and esophageal adenocarcinoma in a cohort of SSc patients.MethodsOne hundred ten SSc patients who were receiving long‐term treatment with proton‐pump inhibitors (PPIs) were assessed systematically by esophageal manometry and endoscopy. Esophageal biopsies were performed when macroscopic abnormalities were detected, and BE was diagnosed histologically.ResultsAmong the 110 patients, 14 had BE (12.7%). None of the patients with BE had adenocarcinoma, but 3 of the 14 patients (21%) had dysplasia on esophageal biopsy. Similar proportions of patients with and without BE had abnormal peristalsis and decreased lower esophageal sphincter pressure. No association between BE and other disease characteristics was demonstrated.ConclusionIn this study, 12.7% of SSc patients who had been treated with PPIs for long periods had BE, similar to the prevalence in patients with gastroesophageal reflux disease. Although none of the patients had esophageal adenocarcinoma, patients with BE should be followed up closely, particularly patients with dysplasic BE. Long‐term prospective studies are warranted to determine the phenotype of SSc patients at high risk of developing dysplasia or esophageal adenocarcinoma.
Fcγ receptor type IIIA polymorphisms influence treatment outcomes in patients with inflammatory arthritis treated with tumor necrosis factor α–blocking agents
Authors: Tutuncu Zuhre , Kavanaugh Arthur , Zvaifler Nathan , Corr Maripat , Deutsch Reena , Boyle David 
Published: September 2005

AbstractObjectiveTo determine whether polymorphisms in Fcγ receptor type IIIA (FcγRIIIA) correlate with clinical efficacy in patients with rheumatoid arthritis (RA) and patients with psoriatic arthritis (PsA) being treated with tumor necrosis factor α (TNFα) inhibitors.MethodsThe study group comprised 30 patients with RA and 5 patients with PsA. Patients were classified as being very good responders (n = 23) or nonresponders (n = 12) to therapy with TNF blocking agents. Whole blood was obtained from all patients, and DNA was extracted for FcγRIIIA analysis. The FcγRIIIA‐158 polymorphism was determined using an allele‐specific polymerase chain reaction assay.ResultsThe distribution of FcγRIIIA‐158 genotypes was as follows: for F homozygous (F/F), 31.5%; for V homozygous (V/V), 11.5%; and for V/F heterozygous (V/F), 57%. Among very good responders, the distribution of alleles was as follows: for F/F, 48%; for V/V, 13%; and for V/F, 39%. Among nonresponders, the distribution of alleles was as follows: for F/F, 0%; for V/V, 8%; and for V/F, 92%. The low‐affinity F/F homozygous genotype was found to be significantly associated with response to TNF inhibitor therapy (P < 0.01 by Fisher's exact test).ConclusionThese results suggest that FcγRIIIA‐158 polymorphisms may affect the outcome of treatment with TNF blocking agents. Better understanding of the factors affecting responses to these agents could result in improved outcomes of treatment.
Tumor necrosis factor receptor I from patients with tumor necrosis factor receptor–associated periodic syndrome interacts with wild‐type tumor necrosis factor receptor I and induces ligand‐independent NF‐κB activation
Authors: Yousaf Nasim , Gould David J. , Aganna Ebun , Hammond Linda , Mirakian Rita M. , Turner Mark D. , Hitman Graham A. , McDermott Michael F. , Chernajovsky Yuti 
Published: September 2005

AbstractObjectiveTo investigate the molecular consequences of expressing mutated forms of tumor necrosis factor receptor I (TNFRI) as found in patients with TNFR‐associated periodic syndrome (TRAPS).MethodsWe cloned and expressed full‐length wild‐type (WT) and T50K and P46L variants of TNFRI using a new tightly regulated doxycycline‐dependent expression system. This system enabled the study of molecular interactions between these receptors at both physiologic and pathophysiologic levels of expression.ResultsWe used chemical crosslinking on the cell surface to show that WT and mutant forms of TNFRI, derived from TRAPS patients, interact in the absence of TNF ligand. Doxycycline‐controlled up‐regulation of one TNFRI allele, either WT or mutant, caused down‐regulation of the other allele, indicating dynamic control of cell surface assembly. We also demonstrated that increased expression of mutant TNFRI (T50K) was associated with a parallel increase in NF‐κB p65 (RelA) subunit activation, which did not occur with increased expression of WT TNFRI.ConclusionThe T50K TRAPS‐related variant is capable of sustaining inappropriate NF‐κB activation, resulting in persistent autoinflammation in target organs such as skin, synovial membrane, and the central nervous system. We conclude that some of the inflammatory processes seen in TRAPS do not involve direct interaction of TNF with its receptors, but that other proinflammatory mechanisms capable of up‐regulating TNFRI expression may cause cellular activation through the NF‐κB signaling pathway.
Involvement of chemokines and type 1 cytokines in the pathogenesis of hepatitis C virus–associated mixed cryoglobulinemia vasculitis neuropathy
Authors: Saadoun David , Bieche Ivan , Maisonobe Thierry , Asselah Tarik , Laurendeau Ingrid , Piette Jean Charles , Vidaud Michel , Cacoub Patrice 
Published: September 2005

AbstractObjectiveTo examine the expression profiles of a large number of genes within typical vasculitic nerve lesions in patients with mixed cryoglobulinemia (MC) vasculitis in order to better characterize the molecules involved in cellular tissue activation and trafficking.MethodsThe quantitative expression of 19 genes coding for cytokines, chemokines, and their receptors in the nerve lesions of 9 patients with hepatitis C virus (HCV)–associated MC vasculitis, 7 with idiopathic polyarteritis nodosa (PAN) (rheumatic disease controls), and 8 patients with noninflammatory idiopathic neuropathy (noninflammatory neuropathy controls) was assessed using a real‐time reverse transcriptase–polymerase chain reaction procedure.ResultsCompared with the noninflammatory controls, HCV‐MC vasculitis patients had a significantly higher expression of Th1 cytokines in vasculitic nerve lesions (mean ± SEM fold increase 33.7 ± 11.6 for interferon‐γ and 7.2 ± 1.9 for tumor necrosis factor α), whereas Th2 cytokines were absent (interleukin‐4 [IL‐4], IL‐5, and IL‐13) or were not significantly different (IL‐10). Chemokines involved in T cell and monocyte trafficking were also significantly up‐regulated in the HCV‐MC vasculitis patients (mean ± SEM fold increase 27.4 ± 8.3 for macrophage inflammatory protein 1α [MIP‐1α], 19.9 ± 5.7 for MIP‐1β, and 7.2 ± 1.5 for CXCR3). Compared with patients with idiopathic PAN, there was a trend toward higher expression of MIP‐1α and CXCR3 in HCV‐MC vasculitis patients (mean ± SEM fold increase 27.4 ± 8.3 versus 5.3 ± 3.4 for MIP‐1α and 7.2 ± 1.5 versus 2.5 ± 0.9 for CXCR3).ConclusionThis study is the first to demonstrate a role of cellular immunity and Th1 lymphocytes in the pathogenesis of HCV‐MC vasculitic nerve lesions.
Cerebral and corpus callosum atrophy in systemic lupus erythematosus
Authors: Appenzeller Simone , Rondina Jane Maryam , Li Li Min , Costallat Lilian T. L. , Cendes Fernando 
Published: September 2005

AbstractObjectiveTo determine cerebral and corpus callosum volumes in patients with systemic lupus erythematosus (SLE), using semiautomatic magnetic resonance imaging (MRI) volumetric measurements, and to determine possible relationships between a reduction in cerebral volume and disease duration, total corticosteroid dose, neuropsychiatric manifestations, and the presence of antiphospholipid antibodies.MethodsWe studied 115 consecutive patients with SLE and 44 healthy volunteers. A complete clinical, laboratory, and neurologic evaluation was performed. MRI scans were obtained through a standardized protocol. Sagittal T1‐weighted images were used for semiautomatic volumetric measurements. We compared SLE patients with controls using the 2‐sample t‐test. Analysis of variance was used to test for differences between groups, followed by Tukey's post hoc test for pairwise comparisons, when necessary. Linear regression was used to analyze the association between cerebral atrophy and disease duration and total corticosteroid dose.ResultsCerebral and corpus callosum volumes were significantly smaller in patients with SLE compared with healthy volunteers (P < 0.001). Reduced cerebral and corpus callosum volumes were related to disease duration (P < 0.001). Patients with a history of central nervous system (CNS) involvement more frequently had a reduction in cerebral and corpus callosum volumes (P < 0.001). Patients with cognitive impairment had significantly reduced corpus callosum and cerebral volumes when compared with SLE patients without cognitive impairment (P = 0.001). Cerebral and corpus callosum volumes were not associated with the total corticosteroid dose or the presence of antiphospholipid antibodies.ConclusionIn patients with SLE, a reduction in cerebral and corpus callosum volumes is associated with disease duration, a history of CNS involvement, and cognitive impairment. The total corticosteroid dose and the presence of antiphospholipid antibodies were not associated with more pronounced atrophy.
An independent role of protective HLA class II alleles in rheumatoid arthritis severity and susceptibility
Authors: van der Helm‐van Mil Annette H. M. , Huizinga Tom W. J. , Schreuder Geziena M. Th. , Breedveld Ferdinand C. , de Vries René R. P. , Toes René E. M. 
Published: September 2005

AbstractObjectiveTo prospectively investigate the effect of the DERAA‐encoding HLA alleles on disease susceptibility and severity in a large cohort of patients with rheumatoid arthritis (RA), and to differentiate protective effects from nonpredisposition by comparing subgroups of patients with an equal amount of predisposition alleles.MethodsHLA class II alleles were determined in 440 patients with early RA and in 423 healthy controls. In order to study the effect of HLA on disease severity, radiographic joint destruction was evaluated, using the modified Sharp/van der Heijde method, during 4 years of followup.ResultsThe presence of DERAA‐encoding HLA–DRB1 alleles conferred a lower risk of developing RA for both the presence and absence of SE alleles (odds ratio 0.6). At all time points, radiographic destruction was significantly less severe in DERAA‐positive patients with 1 SE allele compared with DERAA‐negative patients with 1 SE allele. Additionally, a protective effect of DERAA was detected in the groups of patients who were prone to having more severe disease because of the presence of anti–cyclic citrullinated peptide antibodies or because of smoking.ConclusionDERAA‐encoding HLA–DRB1 alleles independently protect against RA and are associated with less severe disease.
RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via toll‐like receptor 3
Authors: Brentano Fabia , Schorr Olivier , Gay Renate E. , Gay Steffen , Kyburz Diego 
Published: September 2005

AbstractObjectiveTo assess the expression of Toll‐like receptor 3 (TLR‐3) protein in synovial tissues and cultured synovial fibroblasts obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate the consequences of stimulation of cultured synovial fibroblasts with TLR‐3 ligands.MethodsTLR‐3 expression in synovial tissues was determined by immunohistochemistry and immunofluorescence, and expression in cultured RA synovial fibroblasts (RASFs) was determined by fluorescence‐activated cell sorting and real‐time polymerase chain reaction techniques. TLR‐3 signaling was assessed by incubating RASFs with poly(I‐C), lipopolysaccharide, palmitoyl‐3‐cysteine‐serine‐lysine‐4, or necrotic synovial fluid cells from RA patients in the presence or absence of hydroxychloroquine or Benzonase. Subsequent determination of interferon‐β (IFNβ), CXCL10, CCL5, and interleukin‐6 (IL‐6) protein production in the culture supernatants was performed by enzyme‐linked immunosorbent assays.ResultsTLR‐3 protein expression was found to be higher in RA synovial tissues than in OA synovial tissues. TLR‐3 expression was localized predominantly in the synovial lining, with a majority of the TLR‐3–expressing cells coexpressing fibroblast markers. Stimulation of cultured RASFs with the TLR‐3 ligand poly(I‐C) resulted in the production of high levels of IFNβ, CXCL10, CCL5, and IL‐6 protein. Similarly, coincubation of RASFs with necrotic synovial fluid cells from patients with RA resulted in up‐regulation of these cytokines and chemokines in a TLR‐3–dependent manner.ConclusionOur findings demonstrate the expression of TLR‐3 in RA synovial tissue and the activation of RASFs in vitro by the TLR‐3 ligand poly(I‐C) as well as by necrotic RA synovial fluid cells, and indicate that RNA released from necrotic cells might act as an endogenous TLR‐3 ligand for the stimulation of proinflammatory gene expression in RASFs.
Selective expansion of a monocyte subset expressing the CD11c dendritic cell marker in the Yaa model of systemic lupus erythematosus
Authors: Amano Hirofumi , Amano Eri , Santiago‐Raber Marie‐Laure , Moll Thomas , Martinez‐Soria Eduardo , Fossati‐Jimack Liliane , Iwamoto Masahiro , Rozzo Stephen J. , Kotzin Brian L. , Izui Shozo 
Published: September 2005

AbstractObjectiveMonocytosis is a unique cellular abnormality associated with the Yaa (Y‐linked autoimmune acceleration) mutation. The present study was designed to define the cellular mechanism responsible for the development of monocytosis and to characterize the effect of the Yaa mutation on the development of monocyte subsets.MethodsWe produced bone marrow chimeras reconstituted with a mixture of Yaa and non‐Yaa bone marrow cells bearing distinct Ly‐17 alloantigens, and determined whether monocytes of Yaa origin became dominant. Moreover, we defined the 2 major inflammatory (Gr‐1+,CD62 ligand [CD62L]+) and resident (Gr‐1−,CD62L−) subsets of blood monocytes in aged BXSB Yaa male mice, as compared with BXSB male mice lacking the Yaa mutation.ResultsAnalysis of the Ly17 allotype of blood monocytes in chimeric mice revealed that monocytes of both Yaa and non‐Yaa origin were similarly involved in monocytosis. Significantly, the development of monocytosis paralleled a selective expansion of the resident monocyte subset compared with the inflammatory subset, and the former expressed CD11c, a marker of dendritic cells. Neither monocytosis nor the change in monocyte subpopulations, including CD11c expression, was observed in Yaa‐bearing C57BL/6 mice, in which systemic lupus erythematosus (SLE) fails to develop.ConclusionOur results suggest that Yaa‐associated monocytosis is not attributable to an intrinsic abnormality in the growth potential of monocyte lineage cells bearing the Yaa mutation and that the Yaa mutation could lead to the expansion of dendritic cells, thereby contributing to the accelerated development of SLE.