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ID PMID Title PublicationDate abstract
18578976 Measurement of biomarkers in juvenile idiopathic arthritis patients and their significant 2008 May OBJECTIVE: To evaluate in juvenile idiopathic arthritis (JIA) patients a biomarker panel of anti-cyclic citrullinated peptide (anti-CCP) antibodies, cartilage oligomeric matrix protein (COMP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IgM rheumatoid factor (RF), IgG RF, and IgA RF and compare to the presence of joint erosions (JE), joint space narrowing (JSN), and synovitis in order to evaluate aggressive disease. METHODS: Sixty-eight JIA patients (19 RF positive polyarthritis, 23 RF negative polyarthritis, 17 persistent oligoarthritis, and 9 systemic-onset) were evaluated using the biomarker panel and compared to 18 healthy controls. All RF isotypes, anti-CCP antibodies, and COMP were measured by enzyme-linked immunosorbent assays (ELISA). Statistically significant differences and associations were assessed for each biomarker in relation to JE, JSN, and synovitis. Multiple regression analysis was used to find the variables associated with joint damage and synovitis. RESULTS: Patients with JE and JSN had significantly elevated levels of IgA RF, IgM RF, and anti-CCP antibodies. COMP levels were higher in early disease, but also later in disease in patients with no JE or JSN. ESR, CRP, and IgA RF were significantly elevated in patients with active synovitis. Regression analysis showed IgM RF and disease duration to be associated with JE and JSN. Anti-CCP antibodies and COMP were also associated with JSN. CRP and IgA RF were associated with synovitis. CONCLUSION: Our findings demonstrate the importance of measuring IgM RF and IgA RF by ELISA and anti-CCP antibodies by ELISA, in addition to COMP in the assessment of JIA patients to determine severity of disease.
18692602 Hepatitis C virus infection and primary Sjögren's syndrome: a clinical and serologic desc 2008 Dec OBJECTIVE: To define the clinical and immunologic profile of 9 patients with Sjögren's Syndrome (SS) and Hepatitis C virus (HCV) infection. PATIENTS: 9 out of 305 patients with SS, diagnosed according to the criteria proposed in 2002, had repeated positive serology for HCV. RESULTS: 9 female patients were studied. The mean age at onset of SS was 59 years, with a mean period of follow-up of 7.1 years. All the patients had glandular manifestations and they were all positive for dacryologic tests. Salivary gland biopsy was performed in 4 patients, all showing characteristic lymphocytic infiltrate. The main extraglandular features were arthralgias, photosensitivity, purpura, thyroiditis. All the patients were positive for anti-nuclear antibodies (ANA): 6 anti-Ro/SSA, 3 anti-Ro/SSA and anti-La/SSB positive. HCV-positive SS were compared with 296 patients with primary SS. They showed higher mean age (p=0.01), higher prevalence of photosensitivity (p=0.0266) and circulating cryoglobulins (p=0.0372). In primary SS, most patients had anti-Ro/SSA antibodies alone (49.8%) or associated to anti-La/SSB (46.5%). Five patients (1.8%) had other ANA specificities. CONCLUSIONS: A chronic HCV infection is concomitant in about 3% of patients with pSS. They differ from patients without HCV infection for the higher prevalence of photosensitivity and cryoglobulins, without clinical manifestations of cryoglobulinemia.
16283417 Successful treatment of a patient with primary Sjögren's syndrome with Rituximab. 2006 Nov We report the course of a 55-year-old woman, the first patient with primary Sjögren's syndrome and distal renal tubular acidosis but without lymphoma to be treated with B-cell depletion using Rituximab. Rapidly after B-cell depletion, remarkable improvement in xerostomia occurred, while serological findings and tubular acidosis have been unchanged. In labial salivary gland biopsy, lymphocyte infiltration and particularly CD20-positive cells decreased strikingly. Aquaporin 1 (AQP-1) expression in myoepithelial cells was very low before treatment and increased noticeably. Apical AQP-5 in acinus cells likewise increased following Rituximab. In contrast, basolateral NKCC1 was expressed at unchanged intensity before and following Rituximab. The improvement has been sustained and still is most gratifying 10 months after treatment. B-cell depletion may be effective treatment in Sjögren's syndrome. Likewise, it may now be possible to separate the immunologic phenomena in Sjögren's syndrome from the consequences of prolonged hyposalivation when studying the pathophysiology of xerostomia.
17435836 [Magnetic resonance imaging of the peripheral joints in psoriatic arthritis]. 2007 Jan OBJECTIVE: Magnetic resonance imaging (MRI) has been widely used for the evaluation of rheumatoid arthritis (RA), with only a minority of studies considering other types of arthritis. This review is concerned with an evaluation of the MRI appearance of peripheral joints in psoriatic arthritis (PsA). METHODS: A Medline search was performed to identify all publications from the years 1985 to 2006 concerning MRI of the peripheral joints and PsA. Additional papers were retrieved by scanning the references to the Medline-listed articles. Articles written in English, French, German, and Italian were included. RESULTS: Most papers studied the hand and wrist, and only few of them were concerned with the knee, foot, temporomandibular joint, and elbow. Patients with PsA showed often, but not always, a pattern of joint inflammation which extended beyond the capsule into the extraarticular tissue. Bone oedema and erosions were less frequent than in RA. In particular, bone oedema at the entheseal junction was seen, especially in the knee. The degree of synovitis, assessed by dynamic MRI, was similar in PsA and RA. DISCUSSION: Data on MRI of the peripheral joints in PsA are scanty. Only few studies were specifically designed to evaluate the pattern of arthritis in PsA, with most information deriving from papers where different types of arthritis were considered together. An enthesis-related origin of PsA has been proposed in contrast to the primarily synovial inflammation of RA. This pathogenic interpretation is likely to be true, but does not explain all cases of PsA, and needs to be confirmed by further studies.
18356174 Sensitivity and specificity of autoantibodies binding to citrullinated carboxyterminal tel 2008 May OBJECTIVE: To assess the specificity and sensitivity of autoantibodies binding to citrullinated carboxyterminal telopeptides of types I and II collagens in an early arthritis series. METHODS: A cohort of 146 patients from the Kuopio 2000 Arthritis Survey having RA, AS, PsA, ReA, uSpA or undifferentiated arthritis were studied. Autoantibodies binding citrullinated types I and II carboxytelopeptides were measured in two different inhibition ELISA assays. Sera from 135 adult persons were used as controls. RESULTS: In RA, the sensitivities were 0.83 with long type I telopeptide and 0.78 with long type II telopeptide and the respective specificities were 0.94 and 0.93, while the corresponding values in other inflammatory joint diseases were much lower. The likelihood ratio in RA increased with longer peptides from 4.20 to 14.06 for type I telopeptide and from 2.74 to 11.67 for type II telopeptide. CONCLUSION: The antibody assay using long telopeptide from type I collagen was the most specific and sensitive method in every diagnostic category, although in the arthritides other than RA, binding was much less abundant and possibly citrulline-independent.
17023811 Henoch-Schönlein purpura after etanercept therapy for psoriasis. 2006 Oct Etanercept is a recombinant dimeric fusion protein consisting of a tumor necrosis factor-alpha receptor ligand-binding region linked to the Fc portion of human IgG. It is approved for use in the treatment of rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, and psoriatic arthritis. Since 1998, there have been reports of vasculitic adverse events, including necrotizing vasculitis and leukocytoclastic vasculitis. In addition, the adverse events reporting system of the U.S. Food and Drug Administration has recorded 35 cases of leukocytoclastic vasculitis, 20 after etanercept therapy and 15 after infliximab. Most cases of cutaneous vasculitis describe development of symptoms within 3 months of etanercept use. In only one case report was direct immunofluorescence performed on tissue and no specific immunoreactivity found. We describe the first case of Henoch-Schönlein purpura with acute renal failure associated with increase in etanercept dose after 11 months of use for treatment of psoriasis. Discontinuation of the drug and treatment with a course of systemic steroids led to the complete resolution of the vasculitis and improvement of renal function. Vasculitis occurring even during chronic use of antitumor necrosis factor agents must be considered as possibly related to the therapy.
16633923 Guidelines for the proper use of etanercept in Japan. 2006 Application of biological agents targeting inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) dramatically caused a paradigm shift in the treatment of rheumatoid arthritis (RA). Infliximab, a chimeric anti-TNF-alpha monoclonal antibody, has initially been introduced to Japan in 2003 and shown to be dramatically effective in alleviating arthritis refractory to conventional treatment. However, serious adverse events such as bacterial pneumonia, tuberculosis, and Pneumocystis jiroveci pneumonia were reported to be in relatively high incidence; i.e., 2%, 0.3%, and 0.4%, respectively, in a strict postmarketing surveillance of an initial 4000 cases in Japan. Etancercept, a recombinant chimeric protein consisting of p75 TNF-alpha receptor and human IgG, was subsequently introduced to Japan in March of 2005. We therefore drew up treatment guidelines for the use of etanercept to avoid potential serous adverse events, since only approximately 150 cases have been included in the clinical study of etanercept in Japan. The guidelines were initially designed by the principal investigators (N.M, T.T., K.E.) of rheumatoid arthritis study groups of the Ministry of Health, Labor and Welfare (MHLW), Japan, and finally approved by the board of directors of the Japan College of Rheumatology. The MHLW assigned a duty to the pharmaceutical companies to perform a complete postmarketing surveillance of an initial 3000 cases to explore any adverse events, and this was performed according to the treatment guidelines shown in this article.
18438876 Safety and efficacy of up to eight years of continuous etanercept therapy in patients with 2008 May OBJECTIVE: To evaluate the safety and efficacy of up to 8 years of etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA). METHODS: Patients with JRA who previously participated in a randomized controlled trial (RCT) of etanercept were eligible to receive etanercept in a long-term open-label extension (OLE) trial. Safety end points included the incidences of serious adverse events (SAEs), medically important infections (MIIs), and death. Efficacy end points included the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement. RESULTS: Of the 69 patients originally enrolled in the RCT, 58 (84%) participated in the OLE, for a total of 318 patient-years of etanercept exposure. A total of 42 of the 58 patients (72%) entered the fourth year of continuous etanercept treatment, and 26 patients (45%) entered the eighth year. Sixteen patients (23% of those entering the RCT) reported 39 SAEs. The overall rate of SAEs (0.12 per patient-year) did not increase with long-term exposure to etanercept. The rate of MIIs (0.03 per patient-year) remained low; 1 new MII was reported in patients with > or =5 years of etanercept exposure. No cases of tuberculosis, opportunistic infections, malignancies, lymphomas, lupus, demyelinating disorders, or deaths were reported. An ACR Pedi 70 response or higher was achieved by 100% of patients with 8 years of data (11 of 11) and by 61% of patients according to the last observation carried forward data (28 of 46). CONCLUSION: These data suggest that the acceptable safety profile of etanercept therapy is maintained for up to 8 years in this population of JRA patients. Improvements in the signs and symptoms of JRA were also maintained for up to 8 years.
16732547 Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile 2006 Jun OBJECTIVE: Previous studies showed that etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA) provided rapid clinical improvement that was sustained for up to 2 years. The goal of our study was to provide data on safety and efficacy after 4 years of etanercept treatment in patients with JRA. METHODS: Patients with active polyarticular-course JRA who participated in an efficacy study continued etanercept treatment in an open-label extension. Safety was assessed by measuring rates of serious adverse events (SAEs) and serious infections. Efficacy was assessed using the American College of Rheumatology (ACR) Pediatric 30 criteria for improvement and standard measures of disease activity. (The ACR Pediatric 30 criteria are defined as improvement of > or = 30% in at least 3 of 6 core response variables used to assess disease activity, with no more than 1 variable worsening by > or = 30%.) RESULTS: Of the 69 patients who enrolled in the original efficacy study, 58 patients (84%) enrolled in the extension, 34 patients received etanercept treatment for > or = 4 years, and 32 of these received complete efficacy assessments. The rate of SAEs was 0.13 per patient-year, and the rate of serious infections was 0.04 per patient-year, in a total etanercept exposure of 225 patient-years. Eighty-two percent of patients who received corticosteroids at any time during the extension were able to decrease their dosage to < or = 5 mg/day prednisone equivalent. Of the 32 patients with complete efficacy data who received etanercept for > or = 4 years, 94% achieved an ACR Pediatric 30 response and 78% achieved an ACR Pediatric 70 response at the last study visit. CONCLUSION: Etanercept offers an acceptable safety profile in children with polyarticular-course JRA and provides significant improvement in disease manifestations that are sustained for > or = 4 years.
17666828 Cell wall beta-glucan derived from Candida albicans acts as a trigger for autoimmune arthr 2007 Aug SKG mice are a recently established experimental model for rheumatoid arthritis (RA). Although they spontaneously develop chronic autoimmune arthritis under conventional conditions, SKG mice failed to develop chronic arthritis in a strictly controlled specific pathogen-free (SPF) environment. Beta-glucan (BG) from Laminaria digitata, laminarin (LAM), induced arthritis under SPF conditions, thus BG would be a pathogenic factor for arthritis in SKG mice. Therefore, we prepared BG from Candida albicans, a pathogenic fungus and investigated whether BG from C. albicans induced arthritis in SKG mice under SPF conditions. SKG mice were injected intraperitoneally with particulate BG (oxidative-Candida albicans (OX-CA)), soluble BG (Candida soluble beta-glucan (CSBG)) from C. albicans and LAM as a positive control. In addition, schizophyllan (SPG) from Schizophyllum commune or Mycobacterium whole cells were injected into SKG mice to induce arthritis. Mice injected with OX-CA, CSBG and SPG had more severe arthritis than with LAM, and whole Mycobacterium cells. IL-6 concentration in sera from SKG mice injected with OX-CA or CSBG was high, whereas not detected in sera from mice treated with LAM. In histological analysis, infiltration of inflammatory cells was observed in SKG mice injected with BG. These results suggest that fungal infection may be a factor to induce and exacerbate autoimmune diseases such as RA.
17203009 Mechanisms of Disease: the role of high-mobility group protein 1 in the pathogenesis of in 2007 Jan High-mobility group protein 1 (HMG1) is a nonhistone nuclear protein that is a prototype of a dual-function alarmin whose immune activity is dependent upon its cellular location. Inside the cell, HMG1 binds to DNA and has a role in transcriptional regulation. Outside the cell, HMG1 acts as a cytokine and has activities that resemble those of tumor necrosis factor. The cytokine activities of HMG1 become manifest when this protein translocates from the nucleus to the cytoplasm and, eventually, into the external milieu; this translocation occurs during cell activation and cell death. Given its cytokine activity, HMG1 has been implicated in the pathogenesis of a broad range of immune-mediated diseases including arthritis. The role for this protein in arthritis was established by observations of the expression of HMG1 in synovial tissue of patients with rheumatoid arthritis as well as in the joints of animals used to model arthritis. Furthermore, in the mouse model of collagen-induced arthritis, treatment with antibodies to HMG1 or to an inhibitory domain of HMG1 can attenuate joint inflammation and damage. These studies identify a novel pathway in the pathogenesis of inflammatory arthritis, as well as a new target for biologic therapy.
17396108 Drug insight: different mechanisms of action of tumor necrosis factor antagonists-passive- 2007 Apr Antagonists of tumor necrosis factor (TNF) have revolutionized the treatment of selected inflammatory diseases. In rheumatology, this has been most notable for ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. Despite their specificity for TNF, these agents, which include the soluble p75 receptor etanercept and the anti-TNF antibodies adalimumab and infliximab, have demonstrated differential clinical efficacy in studies of rheumatoid arthritis; patients who do not respond to one antagonist often respond to another. Therapeutic disparity of these agents is also seen in specific diseases, most notably Crohn's disease. Differences in pharmacodynamics, pharmacokinetics and mechanisms of action, as well as disease heterogeneity, have been proposed to account for these effects. Reverse signaling by transmembrane TNF in response to anti-TNF antibodies, but not soluble receptor, might also influence the therapeutic response.
19005432 Adalimumab-induced acute myelogenic leukemia. 2008 Dec Newer biological treatment strategies have been developed in the last decade with some promising outcomes. Their safety, however, has been questioned lately with multiple reports of increased risk for malignancies and infectious complications. These reports render their use suboptimal. We report a 44-year-old woman receiving adalimumab (Humira) for advanced juvenile rheumatoid arthritis who then developed acute myelogenic leukemia.
18402078 [Vertebral arteriovenous fistula as a complication of atlantoaxial transarticular screw fi 2008 Mar We report a rare case of a vertebral arteriovenous fistula that developed as a complication of atlantoaxial transarticular screw fixation. The patient was a 44-year-old male with a history of juvenile rheumatoid arthritis. He had undergone an atlantoaxial transarticular screw fixation for an atlantoaxial dislocation. At 2 months after the surgery, he complained of right-side tinnitus. A selective left vertebral angiography showed a high-flow arteriovenous fistula of the right V2 segment and occulusion of the right vertebral artery at the level of the C3 vertebral body. Endovascular embolization of the arteriovenous fistula was successfully performed using detachable coils. No deficits were observed after the treatment, and the tinnitus disappeared completely. Endovascular coil embolization is currently an effective and safe treatment for the vertebral arteriovenous fistula.
16287931 Systemic cytokine levels and the effects of etanercept in TNF receptor-associated periodic 2006 Jan OBJECTIVE: To investigate the levels of the pro-inflammatory cytokines IL-6, TNF-alpha, IL-1beta, IL-8, IL-10 and IL-12p70 in the plasma of patients with TNF receptor-associated periodic syndrome (TRAPS) in relation to CRP levels and treatment with etanercept. METHODS: Cytokine concentrations were measured in sequential plasma samples obtained from eight patients with a C33Y mutation in TNFRSF1A and diagnosed with TRAPS, using cytokine bead array. The TRAPS samples were compared with samples from normal controls and rheumatoid arthritis patients. RESULTS: Levels of IL-6 were significantly elevated in C33Y TRAPS patients and these correlated with CRP levels in some of the patients. IL-8 levels were also significantly elevated in the TRAPS patients. However, neither TNF-alpha nor IL-1beta demonstrated a similar increase. This differed from the patients with rheumatoid arthritis, for whom levels of IL-6, IL-8, TNF-alpha, IL-1beta and IL-10 were significantly elevated. The levels of detectable TNF-alpha in the TRAPS patients' plasma were elevated during etanercept treatment. CONCLUSIONS: The cytokine profile of C33Y TRAPS differs from that of a typical autoimmune inflammatory condition such as rheumatoid arthritis, as only IL-6 and IL-8 were elevated in C33Y TRAPS patients, as distinct from a generalized elevation of pro-inflammatory cytokines. However, only some of the C33Y patients tested showed a relationship between elevated IL-6 and CRP. This is consistent with clinical observations that there is marked heterogeneity between individuals with TRAPS, including those in the same family cohort. Although etanercept has a therapeutic effect in some TRAPS patients, it induces increased plasma concentrations of TNF-alpha, possibly by increasing TNF-alpha stability.
17336830 Reactive oxygen species (ROS), but not nitric oxide (NO), contribute to strain differences 2007 There is extensive evidence for the critical role of reactive oxygen species (ROS) and nitric oxide (NO) produced by phagocytes in development of inflammatory processes and pathogenesis of numerous diseases, including rheumatoid arthritis (RA). Apart from their function as mediators of inflammation and tissue damage, recent research supports their role as signaling and regulatory molecules. In the present study we have investigated the production of ROS and NO over the course of adjuvant arthritis (AA) and oil-induced arthritis (OIA), by resident peritoneal macrophages of two rat strains: Dark Agouti (DA), susceptible, and Albino Oxford (AO), resistant to induction of AA and OIA. We have compared levels of ROS and NO produced by susceptible vs. resistant rat strain, and investigated their relevancy for arthritis development and severity. In addition, we have stimulated macrophages in vitro with Mycobacterium bovis BCG, and two heat shock proteins (HSP): endogenous HSP47 and mycobacterial HSP71 (mHSP71). Our results suggest a possible contribution of increased ROS production to arthritis resistance of AO rats. The ROS production in AO rats is potentiated by endogenous HSP47, but not with mycobacterial cell and mHSP71, suggesting HSP47 participates in AA control. We have found no fundamental relationship between the magnitude of NO production and AA and OIA susceptibility and severity, suggesting that NO has no effector role in AA and OIA. Our results advocate a regulatory type action of NO molecule might be more significant in arthritis development.
17982100 Overexpression of Bcl(XL) in B cells promotes Th1 response and exacerbates collagen-induce 2007 Nov 15 B cells play a pathogenic or regulatory role in many autoimmune diseases through production of autoantibodies, cytokine production, and Ag presentation. However, the mechanisms that regulate these B cell functions under different autoimmune settings remain unclear. In the current study, we found that when B cells overexpress an antiapoptotic gene, Bcl(XL), they significantly increased production of IFN-gamma and enhanced Th1 response. Consistently, Bcl-x(L) transgenic mice developed more severe and sustained collagen-induced arthritis due to the enhanced Th1 response. The production of autoantibodies in Bcl(XL) transgenic mice was comparable to that in wild-type mice. Thus, our results indicate a novel role of Bcl(XL) in regulating B cell functions and immune responses. In patients with rheumatoid arthritis, arthritogenic B cells often up-regulate Bcl(XL) expression, which may not only render B cells resistant to apoptosis but also alter the ability of the autoreactive B cells to produce cytokines and modulate the inflammatory response. This may have therapeutic implications if Bcl(XL) expression can be down-regulated in autoreactive B cells.
19035501 Biochemical markers of bone turnover associated with calcium supplementation in children w 2008 Dec OBJECTIVE: To determine the effects of calcium supplementation on bone physiology in corticosteroid-free children with juvenile rheumatoid arthritis (JRA) by measuring serum and urinary bone-related hormones, minerals, and markers of bone formation and resorption. METHODS: In this double-blind trial, patients were randomized to receive daily oral supplementation with 1,000 mg of calcium and 400 IU of vitamin D or with placebo and 400 IU of vitamin D for 24 months. The effect of calcium supplementation on bone physiology was determined periodically using markers of bone turnover. RESULTS: One hundred ninety-eight patients met the inclusion criteria and were followed up in the study. At baseline, there were no differences in markers of bone turnover between the groups. Patients with < or = 4 joints with active disease had higher serum levels of calcium and parathyroid hormone (PTH). Calcium-treated patients with < or =4 joints with active disease had lower levels of osteocalcin (OC). At followup, levels of 1,25-dihydroxyvitamin D3, PTH, OC, and urine phosphorus were lower in the group receiving calcium supplementation. Hypercalciuria, as determined by the urinary calcium-to-creatinine ratio, was not noted in 24-hour urine studies. CONCLUSION: Levels of markers of bone physiology were significantly decreased in children with JRA receiving calcium supplementation. The physiologic changes were noted as early as 12 months into calcium supplementation. The hypercalciuria noted on spot testing of the urinary calcium-to-creatinine ratio was not demonstrated on further evaluation, nor did it lead to renal pathology. These findings suggest that the calcium supplementation met physiologic needs and caused an increased calcium loss in urine.
16802360 A randomized controlled trial of calcium supplementation to increase bone mineral density 2006 Jul OBJECTIVE: To examine the effects of daily supplementation with calcium (Ca) in combination with vitamin D on total body and lumbar spine bone mineral density (BMD) in patients with juvenile rheumatoid arthritis (JRA) who had not taken corticosteroids for at least 3 months prior to the beginning of the study. METHODS: One hundred ninety-eight children and adolescents (141 girls and 57 boys) with JRA, ages 6 to 18 years, with a mean +/- SD age of 11.7 +/- 3.3 years and a mean +/- SD disease duration of 5.6 +/- 3.8 years at the beginning of the study, were enrolled in this randomized double-blind, placebo-controlled trial to receive either daily oral supplements of 1,000 mg of Ca and 400 IU of vitamin D (n = 103) or matched placebo tablets and 400 IU of vitamin D (n = 95) for 24 months. Total body BMD (TBBMD) was measured by dual x-ray absorptiometry at baseline and every 6 months for 24 months. RESULTS: At baseline, the mean +/- SD TBBMD was 0.89 +/- 0.14 gm/cm2 among patients randomized to the Ca group and 0.87 +/- 0.14 gm/cm2 among those randomized to placebo (P = 0.445). At 24 months, the mean +/- SD TBBMD among those receiving Ca was 0.95 +/- 0.13 gm/cm2, compared with 0.92 +/- 0.14 gm/cm2 among those receiving placebo. A longitudinal random-effects mixed model analysis that controlled for differences in the subject's initial BMD, sex, Tanner stage, adherence to the study medication regimen, and body composition revealed significantly higher TBBMD among patients who received Ca compared with patients who received placebo during the study period (P = 0.03). CONCLUSION: Ca supplementation resulted in a small, but statistically significant, increase in TBBMD compared with placebo in children with JRA.
18446009 [Role of IL-6 in the development and pathogenesis of CIA and EAE]. 2008 Apr Interleukin (IL)-6 is a pleiotropic cytokine that has crucial roles in the regulation of immune response, inflammation and hematopoiesis. Recently, a new inflammatory helper T cell subset which produces IL-17A (IL-17), termed Th17 cells was identified and has been reported to be involved in the development and pathogenesis of collagen induced arthritis (CIA) and experimental autoimmune encephalomyelitis (EAE), which are known as the mouse model of rheumatoid arthritis and multiple sclerosis, respectively. It has been demonstrated that IL-6 together with TGF-beta induces the differentiation of Th17 cells from naive helper T cells in vitro. However, IL-6 independent pathway of Th17 differentiation has also been reported, suggesting that the role of IL-6 in vivo in these diseases remains unclear. With the treatment of anti-IL-6R antibody in CIA and EAE, we could suppress the differentiation of antigen specific Th17 cells and the onset of diseases. These results indicate that IL-6 is involved in the induction of Th17 cells in vivo, and anti-IL-6R antibody might be a promising therapy of Th17-mediated autoimmune diseases.