bluuebunny/crossref_metadata_2025 huggingface dataset:
The mutations in the fibronectin gene described in japanese patients with systemic sclerosis are not present in dutch patients
Authors: Verheijen Ron , Oberyé Elna H. , van Venrooij Walther J. , van den Hoogen Frank H. J.
Published: February 2007

Recently, a mutant fibronectin gene was identified in skin fibroblasts obtained from sclerotic lesions of 7 Japanese patients with systemic sclerosis (SSc). Two point mutations were found adjacent to the cell‐attachment tetrapeptide DNA sequence in exon 7 of the fibronectin gene. In the present study, we investigated whether these point mutations are present in the fibronectin gene of Dutch patients with SSc. We were unable to demonstrate the point mutations in the Dutch SSc patients studied.
Detection and quantification of human anti‐Sm antibodies using synthetic peptide and recombinant SmB antigens
Authors: Hines John J. , Elkon Keith B. , Danho Waleed
Published: February 2007

Anti‐Sm–positive sera from patients with systemic lupus erythematosus (SLE) recognize a major epitope located within the carboxyl‐terminal 27 amino acids of a recombinant SmB fusion protein. To determine whether a synthetic peptide corresponding to this region could be used as an antigen to detect anti‐Sm antibodies, sera were typed as anti‐Sm positive or anti‐Sm negative by counterimmunoelectrophoresis (CIE). Twenty‐three SLE sera that were anti‐Sm positive by CIE, 22 that were anti‐Sm negative by CIE, and 42 sera from patients with other autoimmune diseases were tested for anti‐Sm antibodies by enzyme‐linked immunosorbent assay (ELISA), using either the synthetic peptide (C27) or a recombinant SmB (rSmB) fusion protein as the antigen. More than 90% of the sera that were anti‐Sm positive by CIE were also positive by both the C27 and rSmB ELISAs, and an additional 2 SLE sera originally typed as anti‐Sm negative were found to be positive (1 by the C27 ELISA, 1 by the rSmB ELISA), due to the greater sensitivity of the ELISAs. In the rSmB ELISA, anti‐Sm antibodies were not detected in any of the sera from patients with other autoimmune diseases, whereas 3 patients with anti–U1 RNP antibodies (1 each with polymyositis, scleroderma, and mixed connective tissue disease) had a positive result in the C27 ELISA. These results indicate that both the C27 synthetic peptide and rSmB are excellent antigens for use in ELISAs to quantify anti‐Sm antibodies.
Increased interleukin‐2 production in response to human type I collagen stimulation in patients with systemic sclerosis
Authors: Hawrylko Eugenia , Mele Carol Ann , Spertus Arlene , Oster Neill , Frieri Marianne
Published: February 2007

Peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) produced increased amounts of interleukin‐2 (IL‐2), in a dose‐dependent manner, in response to stimulation with human type I collagen, whereas PBMC from normal subjects did not. At a dose of 50 μg human type I collagen/106 PBMC, PBMC from SSc patients (n = 17) produced 8 times as much IL‐2 as did PBMC from 16 normal subjects (P < 0.005) and 3 times as much as did PBMC from a group of 13 rheumatoid arthritis patients (P < 0.05). In contrast, IL‐2 production by PBMC after nonspecific stimulation with the mitogen, phytohemagglutinin, did not differ among the SSc, rheumatoid arthritis, and normal control groups. Cell depletion experiments indicated that the IL‐2‐producing cells in SSc patients are CD4+. Thus, SSc patients have CD4 cells that are specifically sensitized to human type I collagen and can produce increased levels of IL‐2. Measurement of IL‐2 production stimulated by human type I collagen may be useful in evaluating disease activity, and further investigation of this process may contribute to the delineation of the pathogenesis of SSc.
Acute familial myositis with a common autoimmune response
Authors: de la Torre Ignacio García , Ramírez‐Casillas Alberto , Hernández‐Vazquez Lourdes
Published: February 2007

In 1986, we diagnosed and treated 4 patients, all members of 1 rural family, who presented simultaneously with a polymyositis‐like syndrome, anticytoplasmic antibodies (on HEp‐2 cells), and precipitating antibodies of anti‐Jo‐1 and anti‐PM‐Scl specificities. Serum samples from these patients reacted by immunodiffusion against serum from a rodent that had been caught in the patients' house. The precipitin line showed complete immunologic identity with anti‐Jo‐1. To study the specificity of this serum‐serum reaction, 2 mice (Mus musculus) and 1 rat (Rattus rattus) from the neighboring areas of the patients' house were caught and killed. Sections of the liver, kidney, spleen, and skeletal muscle were processed for histopathologic examination and for direct and indirect immunofluorescence studies of the patients' sera. The rodents' sera were tested by immunodiffusion against serum samples from 25 patients with systemic lupus erythematosus, 11 with rheumatoid arthritis, 6 with mixed connective tissue disease, and 11 with various other rheumatic diseases, as well as 16 healthy controls. A serum‐serum precipitin reaction was noted between the rodents' sera and sera from 2 of the patients with polymyositis‐like syndrome. A distinct, but weaker, reaction was found with 2 lupus patients' sera (8%), and with 1 healthy control serum (6%). The rodents' sera were antinuclear antibody positive by indirect immunofluorescence on HEp‐2 cells. These results, suggest that some rodents could be carriers of an as‐yet‐unknown transmissible agent that, in susceptible individuals, induces clinical and serologic manifestations similar to those of polymyositis.
A pair of monozygotic twins who are concordant for myasthenia gravis but became discordant for systemic lupus erythematosus post‐thymectomy
Authors: Grinlinton Fiona M. , Lynch Nora M. , Hart Hamish H.
Published: February 2007

We describe a pair of monozygotic twins who are concordant for myasthenia gravis but discordant for systemic lupus erythematosus (SLE). SLE developed in twin 1 18 years post‐thymectomy and has been characterized by recurrent transverse myelitis and optic neuritis. Twin 2 remains well post‐thymectomy, except for a skin rash and persistent leukopenia. Both twins have developed autoimmune thyroid disease. We review genetic and environmental factors of importance in the pathogenesis of SLE and discuss the possible role of thymectomy in the etiology of the disease.
Regression of reactive systemic amyloidosis due to ankylosing spondylitis following the administration of colchicine
Authors: Escalante Agustin , Ehresmann Glenn R. , Quismorio Francisco P.
Published: February 2007

We describe a patient in whom nephrotic syndrome due to renal amyloidosis occurred 4 years into the course of severe ankylosing spondylitis with peripheral joint and extraarticular involvement. Treatment with colchicine was accompanied by reversal of proteinuria, and histologic regression of amyloid deposits was documented from bone marrow obtained from the femoral heads during total hip arthroplasties staged 1 year apart.
Occupation, income, and education as independent covariates of arthritis in four national probability samples
Authors: Leigh J. Paul , Fries James F.
Published: February 2007

The strong associations between education level and prevalence and severity of arthritis have recently been investigated, with some suggestion that the relationships might be causal. Data from 4 national probability samples were analyzed, in which occupation and income were measured currently and prior to the development of arthritis. These data indicate that previous studies overestimated the strength of the association between schooling and arthritis because income and, especially, occupation were not analyzed as separate covariates. The overestimate appears to be especially high for persons currently employed, for men, and for persons employed in dangerous jobs. Health policy strategies directed toward reducing arthritis rates require not simply a focus on education, but the additional socioeconomic status dimensions of income and occupational safety and health.
Phospholipase A2 is a Major Component of the Salt‐Extractable Pool of Matrix Proteins in Adult Human Articular Cartilage
Authors: Recklies Anneliese D. , White Chantal
Published: February 2007

Adult human articular cartilage contains a component with an apparent molecular weight of 16 kd, which is extractable with high ionic strength buffers. This protein, which, in addition to lysozyme, is one of the most prominent components in salt extracts of adult cartilage, is not detectable in cartilage from newborns. We performed N‐terminal sequence analysis to identify the protein. The amino acid sequence obtained for the first 20 residues was identical to that reported for phospholipase A2 (PLA2) from human placenta and human synovial cells. The extractable PLA2 was found to be active. The lack of PLA2 in salt extracts from newborn cartilage observed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis was confirmed by the very low levels of PLA2 activity detectable in these preparations. PLA2 was clearly present in cartilage extracts from an 18‐year‐old subject and a 19‐year‐old subject, suggesting that its accumulation begins at some stage during the adolescent growth period. The enzyme does not appear to be released from cartilage matrix under normal physiologic conditions, and it is possible that the accumulation of PLA2 in maturing cartilage is a result of the decreased matrix turnover associated with the termination of skeletal growth. Whether PLA2 is active in the cartilage matrix, its precise localization, and its effects on the resident chondrocytes remain to be determined.
Correlation of Serum Interleukin‐6 Levels with Joint Involvement and Thrombocytosis in Systemic Juvenile Rheumatoid Arthritis
Authors: de Benedetti Fabrizio , Massa Margherita , Robbioni Piera , Ravelli Angelo , Burgio Giuseppe R. , Martini Alberto
Published: February 2007

We measured interleukin‐6 (IL‐6) levels in 70 serum samples obtained from 25 patients with systemic‐onset juvenile rheumatoid arthritis (JRA), using the hybridoma cell line B9. Patients with systemic‐onset JRA had significantly elevated serum IL‐6 levels during active disease (mean ± SD 92.1 ± 75.1 hybridoma growth factor units/ml; P < 0.00001 versus healthy age‐matched controls), but not during remission. Serum IL‐6 levels correlated with the extent and severity of joint involvement (P < 0.001) and with platelet counts (P < 0.05). Our data suggest that IL‐6 plays a significant role in the pathogenesis of systemic‐onset JRA.
Suppression of Collagen‐Induced Arthritis by Combination Cyclosporin a and Methotrexate Therapy
Authors: Brahn Ernest , Peacock Derek J. , Banquerigo Mona Lisa
Published: February 2007

Louvain (LOU) rats were administered either methotrexate (MTX; 0.3 mg/kg/week or 0.8 mg/kg/week intraperitoneally), cyclosporin A (CSA; 4 mg/kg/day or 10 mg/kg/day continuous infusion via osmotic pump), or a combination of both agents. The rats were immunized with native type II collagen (CII) to determine the effects of these agents on collagen‐induced arthritis, an animal model of rheumatoid arthritis. A significant decrease in the incidence (P < 0.01) and severity of arthritis by clinical (P < 0.05) and radiographic assessments (P < 0.05) was found in recipients of combination therapy, compared with controls. Delayed‐type hypersensitivity reactions to CII were measured on day 26, and production of IgG antibody to CII was measured on days 7, 14, and 26. IgG antibody was evident by day 7, and titers were near‐maximal by day 14. Both delayed‐type hypersensitivity and antibodies to CII were reduced in animals that received the higher dosage of CSA. Liver, kidney, and spleen specimens obtained from rats treated with CSA and MTX demonstrated no histologic abnormalities on light microscopy, compared with controls. These studies indicate that CSA and MTX in combination is a safe and effective therapy for collagen‐induced arthritis and may be useful in the treatment of rheumatoid arthritis.
The Anticollagenolytic Potential of Lymecycline in the Long‐Term Treatment of Reactive Arthritis
Authors: Lauhio Anneli , Sorsa Timo , Lindy Otso , Suomalainen Kimmo , Saari Herkko , Golub Lorne M. , Konttinen YrjöT.
Published: February 2007

Objective. We sought to determine the antiinflammatory properties of lymecycline in the long‐term treatment of reactive arthritis (ReA).

Methods. Quantitative assay of collagenase activity by densitometry after sodium dodecyl sulfatepolyacrylamide gel electrophoresis.

Results. Therapeutic levels of lymecycline do not directly inhibit the activity of human neutrophil interstitial collagenase, but can prevent the oxidative activation of latent human neutrophil collagenase.

Conclusion. This non‐antimicrobial, anticollagenolytic property of lymecycline may contribute to its therapeutic efficacy in the treatment of patients with ReA.
Bone Marrow Changes in Adjuvant‐Induced and Collagen‐Induced Arthritis
Authors: Hayashida Kenji , Ochi Takahiro , Fujimoto Masahiro , Owaki Hajime , Shimaoka Yasunori , Ono Kero , Matsumoto Keishi
Published: February 2007

Objective. To investigate the role of bone marrow in arthritis.

Methods. Bone marrow changes over time were investigated in rats with adjuvant‐induced and collagen‐induced arthritis, using bioassay techniques and histologic analysis.

Results. In both animal models, bone marrow interleukin‐1 and interleukin‐6 activity began to rise before the onset of arthritis and increased in relation to the progression of arthritis. Enhanced myelopoiesis in the bone marrow was noted in conjunction with the increased cytokine activity.

Conclusion. Bone marrow changes such as those demonstrated in this study may be common to various models of induced arthritis and may have an important role in the pathogenesis of this disease.
Novel genetic markers of rheumatoid arthritis in chilean patients, by dr serotyping and restriction fragment length polymorphism analysis
Authors: González Alfonso , Nicovani Sandra , Massardo Loreto , Bull Paulina , Rodríguez Luis , Jacobelli Sergio
Published: February 2007

Objective. The analysis of genetic markers of rheumatoid arthritis (RA) in a population in which the DR4 serotype is not strongly associated with the disease.

Methods. Chilean RA patients (56 seropositive and 22 seronegative) and 141 controls were studied by serotyping. Southern blot analysis of Bam HI restriction fragment length polymorphism (RFLP) was done in genomic DNA from 46 patients with seropositive RA, 17 patients with seronegative RA, and 45 controls, using a complementary DNA probe specific for DRB1 genes.

Results. The prevalence of the HLA—DR9 haplotype was strikingly higher in seropositive RA patients (21%) than in controls (3%) (Pcorr < 0.0008, by Fisher's exact test; relative risk [RR] = 9.34). The prevalence of DR4 and DR1 haplotypes, although slightly increased, did not achieve a significant preponderance. The simultaneous presence of two Bam HI fragments (3.6 kb and 4.5 kb) was found with higher prevalence in seropositive patients (83%; RR = 9; Pcorr < 0.00002) than in controls (36%), and seemed higher in seronegative RA patients as well (71%; RR = 4). Furthermore, its prevalence remained increased in comparisons of DR4 positive controls (36%) with DR4 positive seropositive patients (100%; RR = 67; Pcorr < 0.0002) and DR4 positive seronegative patients (100%; RR = 36; Pcorr < 0.006), even after excluding the DR9 positive individuals. A tendency toward higher association with DR1 seropositive RA patients (67%; RR = 12), a group with no DR4 or DR9 positive individuals, than in DR1 positive controls (14%), was also observed.

Conclusion. The HLA—DR9 haplotype was definitively consolidated as a very strong genetic marker exclusively for seropositive RA in Chilean patients, as suggested by our previous observations. RFLP analysis showed that the simultaneous presence of 3.6‐kb and 4.5‐kb Bam HI fragments constituted a better RA marker than did any of the heretofore studied haplotypes. These fragments together would be linked to RA independently of the DR1, DR4, and DR9 haplotypes. The overall evidence indicates that Chilean seropositive RA patients display a genetic background that is different from that underlying RA susceptibility in other populations and suggests the existence of common, as well as distinct, genetic elements predisposing to seronegative and seropositive RA.
Impairment of osteophyte formation in hyperglycemic patients with type II diabetes mellitus and knee osteoarthritis
Authors: Horn Claire A. , Bradley John D. , Brandt Kenneth D. , Kreipke Donald L. , Slowman Sally D. , Kalasinski Lorrie A.
Published: February 2007

Objective. Since insulin is a potent growth factor for connective tissue, the present study was designed to investigate whether radiographic features of knee osteoarthritis (OA) in patients with poorly controlled, insulin‐resistant type II diabetes mellitus differ from those in nondiabetic controls with knee OA.

Methods. Radiographs from 25 female patients with diabetes and knee OA were compared with those from 48 female controls who were similar with respect to age, weight, and duration of OA symptoms.

Results. Although the 2 groups were similar with respect to the frequency and severity of joint space narrowing, subchondral sclerosis, and geodes, osteophytes were less common in the patients with diabetes (P = 0.044), and spurring, when present, tended to be ‘marked’ less often in the diabetic patients than in the controls.

Conclusion. The data suggest that diminished availability of insulin at the cellular level or diabetic microvascular disease attenuates the chondro‐ and osteogenesis required for osteophyte formation in the joints of patients with OA.
Barriers to return to work among persons unemployed due to arthritis and musculoskeletal disorders
Authors: Straaton Karin V. , Maisiak Richard , Wrigley J. Michael , White Mary B. , Johnson Philip , Fine Philip R.
Published: February 2007

Objective. To identify barriers to return to work (RTW) among persons likely to be seen in a clinician's practice who are unemployed due to arthritis and musculoskeletal disorders.

Methods. Two hundred eighteen persons unemployed due to arthritis and musculoskeletal disorders were interviewed at baseline and followed up for 1 year, at which time their work status was ascertained. Backward stepwise logistic regression was used to determine the association of baseline clinical, sociodemographic, and work‐related factors to their work status at 1 year of followup.

Results. Fifty‐one (24%) of 216 initially unemployed subjects had returned to permanent paid employment of ≥20 hours/week after 1 year. Having rheumatoid arthritis, Social Security Disability Insurance (SSDI) status, a high pain level, older age, and lower education were barriers to reemployment.

Conclusion. This study establishes the importance of chronic pain and having rheumatoid arthritis as factors independently associated with failure to RTW among persons unemployed due to arthritis and musculoskeletal disorders. The importance of SSDI beneficiary status, age, and education level in RTW is further confirmed. Duration of unemployment or previous work factors were not predictors of RTW in this group.
Responsiveness of human T lymphocytes to bacterial superantigens presented by cultured rheumatoid arthritis synoviocytes
Authors: Tsai Carlene , Diaz Luis A. , Singer Nora G. , Li Lan Lan , Kirsch Anita H. , Mitra Raj , Nickoloff Brian J. , Crofford Leslie J. , Fox David A.
Published: February 2007

Objective. Type B fibroblastic synoviocytes are abundant in inflamed joints of patients with rheumatoid arthritis (RA), and can secrete cytokines and other mediators of inflammation. The aim of this study was to determine whether cell lines derived from RA type B synoviocytes could also serve as accessory cells for T lymphocyte activation.

Methods. Cells from RA synoviocyte lines, with or without preculture in interferon‐γ (IFNγ), were cultured with purified peripheral blood T cells, in the presence or absence of superantigens or other accessory cell–dependent T cell mitogens. T cell proliferation was measured by thymidine incorporation, and synoviocyte surface markers were analyzed by flow cytometry.

Results. RA type B synoviocyte lines were potent accessory cells for T cell responses to bacterial superantigens or lectins, and direct cell‐cell contact was required. Preculture in IFNγ augmented synoviocyte expression of major histocompatibility complex (MHC) class II molecules and of ligands for some T cell costimulatory receptors, but synoviocyte accessory cell function was evident even in the absence of IFNγ. Blocking studies using monoclonal antibodies supported the notion of a role for CD2, CD11a/CD18 and MHC class II molecules in synoviocyte‐dependent T cell activation. Monoclonal antibodies against IFNγ, interleukin‐1β (IL‐1β), IL‐6, IL‐8, and tumor necrosis factor α failed to block the T cell proliferative responses, but anti–IL‐2 was strongly inhibitory.

Conclusion. Cultured RA type B synoviocytes can perform some of the functions of professional antigen‐presenting cells. If such cells have similar properties in vivo, they may be important participants in activation of immune responses, in addition to their previously described synthetic and proinflammatory roles. If RA synovial tissue T cells, like normal peripheral blood T cells, can respond to superantigens presented by synoviocytes, this interaction could be important in the pathogenesis of RA.
Activation of transcription factor NF‐κB in human synovial cells in response to tumor necrosis factor α
Authors: Fujisawa Koushi , Aono Hiroyuki , Hasunuma Tomoko , Yamamoto Kazuhiko , Mita Shiro , Nishioka Kusuki
Published: February 2007

Objective. To examine whether nuclear factor κB (NF‐κB) is activated in cultured synovial cells in response to tumor necrosis factor α (TNFα) and to investigate the correlation between NF‐κB activation and synovial cell proliferation.

Methods. Activation of NF‐κB was detected by electrophoretic mobility shift assay. The transcription of several NF‐κB–dependent genes was evaluated by reverse transcriptase polymerase chain reaction and transient expression assay using human immunodeficiency virus–long terminal repeat chloramphenicol acetyltransferase. Proliferative activity was determined by measurement of 3H‐thymidine incorporation.

Results. Stimulation of synovial cells with TNFα activated NF‐κB and subsequent transcription of several genes. Treatment of synovial cells with N‐acetyl‐L‐cysteine (NAC), an antioxidant agent, inhibited TNFα‐induced NF‐κB activation and transcription. Moreover, NAC also inhibited synovial cell proliferation induced by TNFα.

Conclusion. Our results suggest that NF‐κB plays a pivotal role in synovial cell activation by TNFα. Thus, suppression of NF‐κB could be a potential therapeutic modality for synovitis such as that of rheumatoid arthritis.
Neutrophil trafficking into inflamed joints in patients with rheumatoid arthritis, and the effects of methylprednisolone
Authors: Youssef Peter P. , Cormack John , Evill Charles A. , Peter Daryl T. , Roberts‐Thomson Peter J. , Ahern Michael J. , Smith Malcolm D.
Published: February 2007

Objective. To investigate the trafficking of circulating blood neutrophils and synovial fluid neutrophils in rheumatoid arthritis (RA) patients and the influence of a 1,000‐mg intravenous pulse of methylprednisolone succinate (MP).

Methods. Neutrophils were isolated from the circulation and from the knee synovial compartments of subjects with RA. Circulating neutrophils were labeled with technetium‐99m hexametazime (99mTc‐HMPAO) and reinjected intravenously. Synovial fluid neutrophils were labeled with indium‐111 oxine and reinjected into the knee from which they were isolated. Gamma camera images were obtained at intervals up to 24 hours post MP. Each patient had a baseline study (no MP) and a study in which MP was administered either 4 hours before (2 patients), 10 minutes before (1 patient), or 30 minutes to 1.5 hours after (6 patients) injection of the radiolabeled neutrophils. Subsequent analysis allowed quantitation of the neutrophil uptake into and clearance from the knee as a function of time.

Results. Nine patients who had not received glucocorticoids in the previous 3 months were studied. MP significantly decreased neutrophil ingress in 13 of the 16 knees studied (almost total inhibition in 5 knees), and this occurred within 1.5 hours of MP administration in all except 1 knee. At 24 hours after MP administration, there was a significant increase in visual analog scale (VAS) scores for well‐being and significant decreases in scores on the modified Health Assessment Questionnaire (P < 0.05), tender joints (P < 0.005), VAS for pain (P < 0.005), and generalized stiffness (P < 0.005), as well as a decrease in the C‐reactive protein level (P < 0.05). MP had no effect on neutrophil egress (2 patients). Two additional patients who were receiving oral glucocorticoids were studied. One of them was clinically unresponsive to oral prednisolone, and MP had no effect on neutrophil ingress. The other patient showed no neutrophil ingress during the baseline study. This was confirmed by the presence of a noninflammatory synovial fluid at arthrocentesis.

Conclusion. Neutrophil ingress into and egress from inflamed joints can be accurately monitored using radiolabeled neutrophils and quantitative gamma camera imaging. MP rapidly and substantially decreases neutrophil ingress into inflamed joints. In contrast, MP has no effect on neutrophil egress from the joint.
Identification of a nucleotide pyrophosphohydrolase from articular tissues in human serum
Authors: Cardenal Antonio , Masuda Ikuko , Haas Arthur L. , Ono Wataru , McCarty Daniel J.
Published: February 2007

Objective. To characterize the nucleotide pyro‐phosphohydrolase (NTPPHase) in human serum.

Methods. NTPPHase activity and kinetic analysis were performed using thymidine monophosphate paranitrophenyl ester (TMPNP) or 32Pγ‐labeled ATP as substrate. Sera were chromatographed (dye column), and peak fractions were analyzed kinetically and by immunoblot using antibodies to 127‐kd articular cartilage vesicle (ACV) NTPPHase as well as to PC‐1 and to 58 kd, two plasma membrane ecto‐NTPPHases. Enzyme activity was measured before and after sample ultracentrifugation.

Results. NTPPHase activity was found in all sera tested (2 normal subjects, 9 arthritis patients). Specific activity was increased 9–32‐fold after chromatography; 60–80% of total activity was recovered in a single peak containing an ∼100‐kd soluble peptide related to the 127‐kd ACV enzyme. The apparent Km of this peptide (TMPNP) was virtually identical to that of the porcine ACV 127‐kd enzyme. No immunoreactivity against PC‐1 or 58‐kd NTPPHase was found.

Conclusion. Human serum NTPPHase is derived from 127‐kd ACV‐related enzyme.
Sensitivity and specificity of anti‐Jo‐1 antibodies in autoimmune diseases with myositis
Authors: Vázquez‐Abad Dolores , Rothfield Naomi F.
Published: February 2007

Objective. To determine the sensitivity and specificity of anti‐Jo‐1 in systemic sclerosis (SSc) patients with and without myositis.

Methods. Immunoblots on HeLa nuclei were used to screen sera from 554 consecutive connective tissue disease patients. Those who had 45–55‐kd bands, all patients with polymyositis/dermatomyositis (PM/DM), and a random selection of SSc, Raynaud's disease, systemic lupus erythematosus, and rheumatoid arthritis patients were also studied by anti–Jo‐1 enzyme‐linked immunosorbent assay and by immunoblots on rabbit pooled aminoacyl‐transfer RNA synthetase.

Results. Anti–Jo‐1 was present only in 8 of the 40 PM/DM patients.

Conclusion. Anti–Jo‐1 is specific for PM/DM.
Numerical scoring systems for the anatomic evolution of osteoarthritis of the finger joints
Authors: Verbruggen Gust , Veys Eric M.
Published: February 2007

Objective. To assess and score the progression of osteoarthritis (OA) of the distal and proximal interpha‐langeal (DIP and PIP) and metacarpophalangeal (MCP) joints.

Methods. Forty‐six patients with OA of the finger joints were followed up for 3 years; 36 of them were followed up for 5 years. Posteroanterior radiographs of the hands were obtained at the start of this prospective study and at yearly intervals. The scoring systems used were based on the increased incidence of OA during consecutive years in previously normal joints, the radiologic progression of the anatomic lesions in the affected finger joints, and the consecutive pathologic phases recognized in the course of the disease.

Results. Significant increases both in the numbers of affected DIP, PIP, and MCP joints per subject and in the anatomic progression of the disease (changes in osteophyte growth, loss of joint space, and subchondral cysts or sclerosis) in the different finger joints of each patient were recorded during the 3 and 5 years of followup. In ∼40% of the patients, the classic picture of OA was complicated by erosive changes, which preceded a period in which repair phenomena in the “eroded” finger joints led to the generation of a new subchondral plate covered by cartilaginous tissue. Huge osteophytes were then responsible for the nodular aspect of the affected finger joints.

Conclusion. OA of the finger joints is progressive in nature and passes through predictable phases. The recognition of and the attribution of a score to these respective phases made assessing the progression of OA less time‐consuming and led to the same conclusions as when the anatomic progression was scored.
Cryocrystalglobulinemia as a cause of systemic vasculopathy and widespread erosive arthropathy
Authors: Papo Thomas , Musset Lucile , Bardin Thomas , Bucki Barbara , Jorgensen Christian , Dion Elisabeth , Quillard Alain , de Gennes Christian , Sany Jacques , Godeau Pierre , Piette Jean‐Charles
Published: February 2007

This report describes the case of a woman who was admitted to the hospital for highly destructive axial and peripheral arthropathy in association with acute malignant hypertension and skin purpura. Type I IgG K serum cryoglobulinemia was identified and was classified as a monoclonal gammopathy of unknown significance. Cryoglobulin was shown to crystallize in the serum and synovium fluid and was responsible for both granulomatous microcrystalline synovial inflammation and occlusive vasculopathy in the kidneys and skin. Cryocrystalglobulinemia pathogenicity and therapeutic implications are discussed.
Failure of low‐dose intravenous immunoglobulin therapy to suppress disease activity in patients with treatment‐refractory rheumatoid arthritis
Authors: Kanik Keith S. , Yarboro Cheryl H. , Naparstek Yaakov , Plotz Paul H. , Wilder Ronald L.
Published: February 2007

Objective. Treatment with high‐dose (400 mg/kg/day) intravenous immunoglobulin (IVIg) shows benefit in many autoimmune diseases but is very expensive. Low‐dose IVIg has also been shown to be effective in inhibiting adjuvant arthritis in the rat. This pilot, randomized, double‐blind, placebo‐controlled trial was conducted to assess the use of low‐dose IVIg in patients with treatment‐refractory rheumatoid arthritis (RA).

Methods. Twenty patients with active RA were recruited. Ten patients received IVIg and 10 received albumin. Study subjects were given 6 courses of either IVIg (5 mg/kg) or albumin (5 mg/kg), once every 3 weeks. Baseline medications were continued and not changed throughout the study.

Results. There were no complications. Five patients dropped out before the 18‐week followup visit. No significant differences between treatment groups were noted during the 18‐week trial in terms of global activity indices (patient or physician assessment), joint swelling, joint pain or tenderness, erythrocyte sedimentation rate, C‐reactive protein level, or rheumatoid factor. The protocol was terminated prematurely because of reported contamination of IVIg by hepatitis C virus. None of the patients showed evidence of hepatitis C infection by serologic analysis or by polymerase chain reaction.

Conclusion. Low‐dose IVIg, as administered in this trial, does not show a therapeutic effect in patients with refractory RA.
A double‐blind, placebo‐controlled study of anti‐CD5 immunoconjugate in patients with rheumatoid arthritis
Authors: Olsen Nancy J. , Brooks Raye H. , Cush John J. , Lipsky Peter E. , St. Clair E. William , Matteson Eric L. , Gold Kenneth N. , Cannon Grant W. , Jackson Christopher G. , McCune W. Joseph , Nelson Betty , Lorenz Todd , Strand Vibeke
Published: February 2007

Objective. To evaluate the efficacy of an anti‐CD5 ricin‐linked immunoconjugate (CD5‐IC) in patients with rheumatoid arthritis (RA).

Methods. A total of 104 evaluable patients were enrolled in a multicenter, double‐blind, multiple‐dose, placebo‐controlled study of CD5‐IC.

Results. Treatment with CD5‐IC in doses up to 8 mg/m2/day for 4 days in 1 month failed to produce marked or prolonged T cell depletion and was no more effective than placebo in ameliorating disease manifestations. An unexpectedly high placebo response was observed in 48% of the patients. Adverse events were correlated with the dose of CD5‐IC, but the treatment was generally well‐tolerated.

Conclusion. At the doses used in this study, CD5‐IC was ineffective for treating RA.
Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis
Authors: Langford Carol A. , Sneller Michael C. , Hallahan Claire W. , Hoffman Gary S. , Kammerer William A. , Talar‐Williams Cheryl , Fauci Anthony S. , Lebovics Robert S.
Published: February 2007

Objective. To determine the clinical features and optimal treatment of subglottic stenosis (SGS) in patients with Wegener's granulomatosis (WG).

Methods. Review of 43 patients with SGS and treatment of 20 patients with intratracheal dilation—glucocorticoid injection therapy.

Results. SGS developed in 43 of 189 patients with WG who were followed up at the National Institutes of Health Clinical Center. The diagnosis of SGS occurred in the absence of other features of active WG in 21 of 43 patients (49%). In 21 patients (49%), SGS began while the patient was receiving systemic immunosuppressive therapy for disease activity involving other sites. Tracheostomy was required in 10 of 18 patients (56%) who were treated with systemic immunosuppressive therapy. In 20 patients treated with intratracheal therapy, none required tracheostomy and 6 with previous tracheostomies were decannulated.

Conclusion. SGS often occurs independently of other features of active WG and is frequently unresponsive to systemic immunosuppressive therapy. Intratracheal dilation—injection therapy provides a safe and effective treatment for WG‐associated SGS and, in the absence of major organ disease activity, should be used without concomitant systemic immunosuppressive agents.
Presence of antibodies to native G1 domain of aggrecan core protein in synovial fluids from patients with various joint diseases
Authors: Karopoulos Christopher , Rowley Merrill J. , Ilic Mirna Z. , Handley Christopher J.
Published: February 2007

Objective. To investigate the occurrence of IgG antibodies to aggrecan in synovial fluids (SF) from patients with arthritis and various articular diseases, and to determine the nature of epitopes present within aggrecan that react with these antibodies.

Methods. SF samples were reacted with native aggrecan, reduced and alkylated aggrecan, chondroitin sulfate, and keratan sulfate, using dot‐blots and a novel enzyme‐linked immunosorbent assay (ELISA). The nature of the epitopes present on aggrecan was elucidated using Western blots and a competitive inhibition ELISA.

Results. IgG antibodies to aggrecan were found in >50% of the SF samples tested. No IgG antibody reactivity was observed in serum from the same patients. The antibodies appeared to react predominantly with native aggrecan, and there was no disease specificity. It was shown that the epitopes to these antibodies were located within the N‐terminal region of the core protein.

Conclusion. This study demonstrates the frequent occurrence of IgG antibodies to aggrecan in human SF. The major epitope is located in the G1 domain of the aggrecan core protein. These IgG antibodies appear to be produced locally within the synovial cavity, probably in response to various articular diseases, resulting in the loss of native aggrecan from articular cartilage.
A randomized, double‐blind study comparing twenty‐four‐week treatment with recombinant interferon‐γ versus placebo in the treatment of rheumatoid arthritis
Authors: Veys Eric M. , Menkes Charles‐Joël , Emery Paul
Published: February 2007

Objective. To evaluate the safety and efficacy of recombinant interferon‐γ (rIFNγ) in patients with active rheumatoid arthritis (RA), using an induction and maintenance regimen.

Methods. A multicenter, randomized, double‐blind trial of 197 patients with RA was conducted to compare the effects in a group receiving 50 μg of rIFNγ, given subcutaneously in a decreasing regimen over 24 weeks, with those in a placebo group receiving injections of placebo at the same time frequency. Standard clinical assessments were performed.

Results. Both rIFNγ and placebo produced a significant improvement from baseline to end point visit for most measurements (except erythrocyte sedimentation rate, duration of morning stiffness, and grip strength), but no significant intergroup differences were seen. Regarding adverse effects, mild local skin reactions at the site of injection were observed, and among the cardiovascular events, mild edema and vasodilatation were reported.

Conclusion. IFNγ proved no more effective than placebo in this group of patients with RA. IFNγ was well tolerated in this group of patients, without increased toxicity compared with placebo.
Rheumatoid arthritis synovial fibroblast and U937 macrophage/monocyte cell line interaction in cartilage degradation
Authors: Scott Boyd B. , Weisbrot Lisa M. , Greenwood Janice D. , Bogoch Earl R. , Paige Christopher J. , Keystone Edward C.
Published: February 2007

Objective. To examine the interaction between synovial fibroblasts and macrophages in the context of cartilage degradation.

Methods. An in vitro model of human cartilage degradation was used, in which purified populations of fibroblasts and macrophages were added to a radio‐labeled cartilage disc. Cartilage destruction was measured by the percentage of radiolabel release.

Results. Fibroblasts, obtained from either rheumatoid arthritis (RA) or osteoarthritis synovial tissue, could mediate cartilage degradation if cocultured with the U937 macrophage cell line. Skin and RA bone marrow fibroblasts had no degradative effect on cartilage. Fibroblast—macrophage contact was not required for cartilage degradation. Cartilage degradation by synovial fibroblasts was inhibited by antibodies to tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), and IL‐6. Cartilage degradation was almost completely abrogated by a combination of antibodies to TNFα and IL‐1β. Contact between fibroblasts and cartilage was shown to be essential. Antibodies to CD44, but not to intercellular adhesion molecule 1, markedly inhibited cartilage degradation.

Conclusion. TNFα, IL‐1β, and IL‐6 were involved in the activation of synovial fibroblasts to cause cartilage degradation. Cartilage degradation occurred only when fibroblasts were in contact with cartilage. CD44 was demonstrated to be involved in the fibroblast—cartilage interaction.
Cr1, CD35 IN synovial fluid from patients with inflammatory joint diseases
Authors: Sadallah Salima , Lach Estelle , Lutz Hans U. , Schwarz Sibylle , Guerne Pierre‐André , Schifferli Jürg A.
Published: February 2007

Objective. To investigate synovial fluid (SF) for the presence of CR1 and to study its relationship to SF leukocytes and to serum levels of soluble CR1 (sCR1) in patients with rheumatic diseases.

Methods. Synovial fluids were collected from 35 patients with rheumatoid arthritis (RA) and 26 patients with other inflammatory joint diseases. Total CR1 in the SF and serum were measured with a sandwich enzyme‐linked immunosorbent assay (ELISA) that recognized both soluble and transmembrane forms of CR1. The characteristics of CR1 in SF were analyzed by ultracen‐trifugation and by a second ELISA specific for trans‐membrane CR1.

Results. CR1 was found in all SF samples tested (range 5‐281 ng/ml). SF CR1 was higher in patients with RA (mean ± SD 81 ± 66 ng/ml) than in those with other inflammatory joint diseases (31.8 ± 23.8 ng/ml) (P < 0.001). Serum sCR1 was not significantly increased in the patients compared with the normal subjects. There was no correlation between serum sCR1 and SF CR1. In 44% of the patients, the SF CR1 level was higher than the serum sCR1 level. A fraction (30–80%) of SF CR1 was pelleted by ultracentrifugation and, unlike serum sCR1, it reacted in an ELISA specific for transmembrane CR1. Thus, SF contained 2 forms of CR1: a membrane‐associated and a soluble form, which was confirmed by sucrose density‐gradient ultracentrifugation. SF CR1 levels correlated directly with the number of SF total leukocytes and polymorphonuclear leukocytes (PMN). These 2 forms of CR1 were also found in the supernatant of in vitro—activated PMN from normal subjects. SF CR1 exhibited the capacity to act as a cofactor for the factor I degradation of C3b.

Conclusion. CR1 is found in the SF of patients with joint inflammation. The data suggest that SF CR1 originates from the infiltrating leukocytes, which shed both a soluble and a membrane‐associated form. Whether SF CR1 participates in the local regulation of complement activation remains to be examined.
Elevated cytokine messenger RNA levels in the peripheral blood of patients with rheumatoid arthritis suggest different degrees of myeloid cell activation
Authors: Schulze‐Koops Hendrik , Davis Laurie S. , Kavanaugh Arthur F. , Lipsky Peter E.
Published: February 2007

Objective. To determine whether monocytes in rheumatoid arthritis (RA) are activated to produce proinflammatory cytokines in the peripheral circulation before entering the synovium and whether the pattern of cytokines that is expressed correlates with disease activity.

Methods. Cytokine messenger RNA (mRNA) levels were assessed in peripheral blood mononuclear cells (PBMC) from 14 RA patients and 14 healthy controls by semiquantitative reverse transcription–polymerase chain reaction technology. The method employed was sufficiently sensitive to assess cytokine mRNA levels in freshly isolated cells without the necessity of in vitro stimulation. Thus, an estimate of the in vivo state of activation could be obtained.

Results. Interleukin‐8 (IL‐8) mRNA levels were elevated in all 14 RA patients compared with normal controls, whereas 7 of 14 RA patients had elevated levels of mRNA for IL‐6 or IL‐10. IL‐1B mRNA levels were below the normal range in 3 of 14 patients, within normal limits in 4 of 14, and elevated in 7 of 14. Tumor necrosis factor a mRNA levels were within the normal range in 9 of 14 patients and below normal in 5 of 14. There was a statistically significant difference between the mean IL‐10 (P < 0.05) and IL‐8 (P < 0.001) mRNA.levels in RA patients and normal controls. Of note, the 7 patients with elevated IL‐lβ mRNA levels also expressed the highest levels of IL‐8 mRNA. Whereas a strong correlation between the expression of IL‐lβ and IL‐8 mRNA (P < 0.001) was found, expression of all other mRNA occurred independently of each other. Levels of cyclooxygenase 2 (COX‐2) mRNA were also determined to evaluate the status of myeloid cell activation more completely. COX‐2 mRNA levels were within the normal range in 4 of 11 patients and below normal in 7 of 11, but did not correlate with the expression of any of the cytokine mRNA.

Conclusion. Elevated levels of mRNA for selected cytokines that are predominantly produced by monocytes can be found in the PBMC of many RA patients. The data indicate that myeloid precursor cells become activated to produce cytokines before they enter the synovium, a finding which emphasizes the systemic nature of RA.
Induction of alternative splicing of HLA‐B27 by bacterial invasion
Authors: Huang Feng , Yamaguchi Akihiro , Tsuchiya Naoyuki , Ikawa Takashi , Tamura Naoto , Virtala Mika M. K. , Granfors Kaisa , Yasaei Parvin , Yu David Tak Yan
Published: February 2007

Objective. Alternative splicing of certain class I major histocompatibility complex pre–messenger RNA (pre‐mRNA) is known to lead to generation of a cell‐free soluble protein analog. This study was undertaken to examine whether this process occurs with HLA–B27, whether the process is modified by arthritis‐causing bacteria, and whether the assembly of the soluble molecules follows the same pathway as the integral parent molecules.

Methods. Alternative splicing of pre‐mRNA was analyzed by reverse transcriptase‐polymerase chain reaction, and assembly of soluble HLA–B27 by immunoprecipitation followed by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and autoradiography.

Results. There was alternative splicing of the pre‐mRNA of HLA–B27. The process could be amplified by invasion with Salmonella or Yersinia bacteria. The soluble HLA–B27 was assembled in a pathway similar to that of the parent molecule.

Conclusion. The association between arthritiscausing bacteria and HLA–B27 positive cells is a complex event. Soluble HLA–B27 is a potential key player.
In vivo direct gene transfer into articular cartilage by intraarticular injection mediated by HVJ (Sendai virus) and liposomes
Authors: Tomita Tetsuya , Hashimoto Hideo , Tomita Naruya , Morishita Ryuichi , Lee Seung Bak , Hayashida Kenji , Nakamura Norimasa , Yonenobu Kazuo , Kaneda Yasufumi , Ochi Takahiro
Published: February 2007

Objective. To establish a system for efficient, direct in vivo gene transfer into joints.

Methods. A hemagglutinating virus of Japan (HVJ; Sendai virus)‐liposome suspension containing SV40 large T antigen (SVT) gene was injected intraarticularly into knee joints of 6‐week‐old female Lewis rats. Rats were killed at various times for immunohistochemical analysis of the expression of SVT gene.

Results. The expression of SVT gene was detected immunohistochemically in chondrocytes in the superficial and middle zones of articular cartilage in the knee joints. The average percentage of SVT‐positive cells was estimated to be ∼30% on days 3, 7, 14, and 21 after transfection. Moreover, no pathologic change caused by HVJ‐liposome injection was observed in the joints.

Conclusion. The transfection frequency and stability of expression recognized in this study indicate the possibility of a strategy for treatment of joint disorders, including arthritis, using direct gene transfer.
Human immunodeficiency virus infection in systemic lupus erythematosus
Authors: Fox Robin A. , Isenberg David A.
Published: February 2007

This report describes a female patient with systemic lupus erythematosus (SLE) who was infected with the human immunodeficiency virus (HIV). Using stored serum, the precise timing of HIV seroconversion was determined and the early effects of HIV infection on SLE examined. This infection resulted in clinical improvement and the disappearance of autoantibody production. A literature review of the association between HIV and SLE is provided.