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ID PMID Title PublicationDate abstract
16424527 Conjunctival epithelium improvement after systemic pilocarpine in patients with Sjogren's 2006 Feb AIM: To evaluate the effect of oral pilocarpine treatment on conjunctival epithelium of patients with Sjögren's syndrome (SS). METHODS: 15 primary SS patients were included in this prospective, single masked, comparative study. Patients underwent oral pilocarpine treatment for 2 months and were studied before (T0) and after 1 month (T1), 2 months (T2), and 15 days after treatment suspension (T3). Systemic and ocular symptoms, tear film break up time (BUT), corneal fluorescein vital staining, Schirmer I test, tear basal secretion test, and conjunctival imprinting were performed. Student's t test and Mann-Whitney U test were used for statistics. RESULTS: The conjunctival imprinting showed an increase of goblet cells number at T1 (1.6 (1.2) v 0.6 (0.7) at T0, p = 0.025) improving at T2 (5.1 (1.7); p<0.001 v T0 and T1). At T3 the number of goblet cells significantly decreased (1.9 (1.1); p<0.001 v T2). An improvement of dry mouth started at T1 and returned towards baseline values at T3. For ocular symptoms, burning and foreign body sensation were improved at T1 while ocular dryness improved at T2. BUT showed a statistically significant improvement at T2. CONCLUSIONS: Oral pilocarpine induced an increase in goblet cells number and an amelioration of conjunctival epithelium not dependent on tear secretion.
17054769 NOD mouse model for Sjögren's syndrome: lack of longitudinal stability. 2006 Nov OBJECTIVES: The non-obese diabetic (NOD) mouse is not only a widely used model for diabetes mellitus type I, but also for the chronic autoimmune disease Sjögren's syndrome (SS), mainly affecting salivary and lacrimal glands. We studied the efficacy of local recombinant serotype 2 adeno-associated viral (rAAV2) vector transfer of immunomodulatory transgenes to alter the SS-like disease in NOD mice. Data collected over a 2-year period indicated a changing SS phenotype in these mice and this phenomenon was investigated. METHODS: 10(10) particles rAAV2LacZ/gland were delivered to both submandibular glands (SMGs) of NOD/LtJ mice at 8 weeks (before sialadenitis onset) of age. Salivary flow rates were determined at 8 weeks and time of killing. Blood glucose levels and body weights were measured weekly. After killing, saliva and SMGs were harvested. Analyses of salivary output, inflammatory infiltrates (focus score), SMG cytokine profile, body weight, and diabetes mellitus status were performed. Data from six different experimental studies over 2 years were analyzed and compared. RESULTS: Salivary flow rate, focus score, and SMG cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12(p70), tumor necrosis factor-alpha and IFNgamma showed changes over time. There were no differences for body weight, diabetes mellitus prevalence, or blood glucose level of non-diabetic mice. CONCLUSION: This retrospective report is the first to describe longitudinal variability in the NOD mouse as a model for SS. We advise other investigators to continuously monitor the SS phenotype parameters and include appropriate controls when studying this disease in NOD mice.
16547229 Desiccating stress induces T cell-mediated Sjögren's Syndrome-like lacrimal keratoconjunc 2006 Apr 1 Chronic dry eye syndrome affects over 10 million people in the United States; it is associated with inflammation of the lacrimal gland (LG) and in some cases involves T cell infiltration of the conjunctiva. We demonstrate that environmental desiccating stress (DS) elicits T cell-mediated inflammation of the cornea, conjunctiva, and LG, but not other organs in mice. The lacrimal keratoconjunctivitis (LKC) was mediated by CD4(+) T cells, which, when adoptively transferred to T cell-deficient nude mice, produced inflammation in the LG, cornea, and conjunctiva, but not in any other organ. Adoptively transferred CD4(+) T cells produced LKC even though recipients were not exposed to DS. LKC was exacerbated in euthymic mice depleted of CD4(+)CD25(+)forkhead/winged helix transcription factor(+) regulatory T cells. The results suggest that DS exposes shared epitopes in the cornea, conjunctiva, and LG that induce pathogenic CD4(+) T cells that produce LKC, which under normal circumstances is restrained by CD4(+)CD25(+)forkhead/winged helix transcription factor(+) regulatory T cells.
16305644 IL-10 promoter -1082 polymorphism is associated with elevated IL-10 levels in control subj 2005 Nov The aim of this study was to investigate the frequency of the -1082 polymorphism of the interleukin-10 (IL-10) gene and the soluble IL-10 levels in Hungarian primary Sjögren's syndrome (SS) patients. Ninety-nine SS patients and 135 healthy volunteers were examined. Samples were analysed by the PCR restriction fragment length polymorphism method, and IL-10 plasma levels were assessed by a commercial enzyme-linked immunosorbent assay. IL-10 plasma levels were higher in the primary SS patients (36.4 +/- 57.5 pg/ml, n = 99) compared with the healthy subjects (9.9 +/- 20.3 pg/ml, n = 135, P = 10(-6)). The elevated IL-10 phenotype of SS patients was not associated with increased G allele frequency as reported earlier, while in the control group, we found higher IL-10 levels among the subjects who were carriers of the GG genotype (17.7 +/- 23.2 pg/ml) as compared with the other two genotype carriers (AA 8.98 +/- 16.5 and GA 8.5 +/- 21.1 pg/ml, P = 0.01). Our data do not support previous observations indicating an association between deregulated IL-10 secretion in SS and higher G allele frequency. However, the results clearly demonstrate that GG homozygosity is associated with elevated IL-10 levels in apparently healthy subjects, but this cannot account for the IL-10-related specific disease features observed in SS. Thus, other genetic factors contribute to the clinical spectrum of this heterogeneous disease at least in the Hungarian population.
16210812 Different effects on the inflammatory lesions in the lacrimal and salivary glands after ne 2005 Sep Thymectomy on day 3 after birth (D3Tx) is understood to eliminate CD4+CD25+ regulatory T cells (Treg) from the peripheral T cell repertoire in rodents, leading to the activation of autoreactive T cells. Herein, D3Tx was performed in IQI/Jic mice, a model for Sjögren's syndrome characterized by autoimmune infiltrations into the lacrimal and salivary glands. At the age of 16 weeks, very severe lesions were observed in lacrimal tissues from thymectomized mice, suggesting that Treg preserve their immunoregulatory function in young IQI/Jic mice. In contrast, salivary lesions were comparable in the D3Tx and control groups, raising the possibility that either salivary-specific Treg escaped elimination in thymectomized mice or spontaneous lesions in IQI/Jic mice developed independently of the tolerance through Treg.
16756750 A new approach to managing oral manifestations of Sjogren's syndrome and skin manifestatio 2006 May 31 Sjogren's syndrome (SS) is an autoimmune disorder that affects the salivary glands, leading to xerostomia, and the lacrimal glands, resulting in xerophthalmia. Secondary SS is associated with other autoimmune disorders such as systemic rheumatic diseases and systemic lupus erythematosis (SLE), which can affect multiple organs, including the epidermis. Recent studies have demonstrated that green tea polyphenols (GTPs) possess both anti-inflammatory and anti-apoptotic properties in normal human cells. Epidemiological evidence has indicated that, in comparison to the United States, the incidence of SS, clinical xerostomia and lupus is considerably lower in China and Japan, the two leading green tea-consuming countries.Thus, GTPs might be responsible, in part, for geographical differences in the incidence of xerostomia by reducing the initiation or severity of SS and lupus. Consistent with this, molecular, cellular and animal studies indicate that GTPs could provide protective effects against autoimmune reactions in salivary glands and skin. Therefore, salivary tissues and epidermal keratinocytes could be primary targets for novel therapies using GTPs. This review article evaluates the currently available research data on GTPs, focusing on their potential application in the treatment of the oral manifestations of SS and skin manifestations of SLE.
16688999 [Effects of Chinese herbal medicine for Yiqi Yangyin Quyu in treating Sjögren's syndrome 2006 Apr OBJECTIVE: To investigate the immuno-regulatory and therapeutic effects of Chinese herbal medicine for Yiqi Yangyin Quyu (YYQ, supplementing qi, nourishing yin, removing blood stasis) on Sjögren's syndrome (SS). METHODS: Sixty-two patients were randomly divided into the treated group (37 cases) treated with Chinese medicine and prednisone, and the control group (25 cases) treated with prednisone alone, and another 20 healthy persons were taken as the normal control group. Curative effects was observed, and immunoglobulin (Ig) and T lymphocyte subsets were detected before and after 3 months' treatment. RESULTS: Immunoglobulin (IgG, IgM and IgA) before treatment in SS patients were higher, while the proportion of natural killer (NK) cell and CD4 were lower as compared with those in the normal control group. After treatment, IgG, IgM and IgA lowered to normal levels (P < 0.05), the proportion of NK cell and CD4 rose in both groups (P < 0.05), but CD3 in the control group was still lower than that in the treated group (P < 0.05). The total curative effective rate in the treated group was 91.9%, better than that in the control group (76.0%, chi-squared = 3.92, P < 0.05). CONCLUSION: Chinese herbal medicine for YYQ could improve clinical curative effective rate and regulate immune function in SS patients.
16339583 Immunization with short peptides from the 60-kDa Ro antigen recapitulates the serological 2005 Dec 15 Sjögren's syndrome is a poorly understood autoimmune inflammatory illness that affects the salivary and lacrimal glands as well as other organ systems. We undertook the present study to determine whether mice immunized with short peptides from the 60-kDa Ro (or SSA) Ag, which is a common target of the autoimmunity of Sjögren's syndrome, develop an illness similar to Sjögren's syndrome. BALB/c mice were immunized with one of two short peptides from 60-kDa Ro that are know to induce epitope spreading. The animals were analyzed for the presence of anti-Ro and anti-La (or SSB) in the sera by immunoblot and ELISA. Salivary glands were collected and examined by histology after H&E staining. Salivary lymphocytes were purified and studied for cell surface makers by fluorescence-activated cell sorting. Timed stimulated salivary flow was measured. As reported previously, BALB/c mice immunized with 60-kDa Ro peptides developed an immune response directed against the entire Ro/La ribonucleoprotein particle that was similar to that found in humans with lupus or Sjögren's syndrome. Functional studies showed a statistical decrease in salivary flow in immunized mice compared with controls. Furthermore, there were lymphocytic infiltrates in the salivary glands of immunized animals that were not present in controls. The infiltrates consisted of both CD4- and CD8+ T lymphocytes as well as B lymphocytes. BALB/c mice immunized with 60-kDa Ro peptides develop anti-Ro, salivary gland lymphocyte infiltrates, and salivary dysfunction that is highly reminiscent of human Sjögren's syndrome.
16014556 Autoimmunity and coxsackievirus infection in primary Sjogren's syndrome. 2005 Jun Exocrine gland epithelial cells are the target of autoimmune pathology in primary Sjögren's syndrome (pSS). Their activated phenotype has incited the notion that they are infected by a virus. We recently presented evidence that coxsackieviruses may persistently infect the salivary glands of pSS patients. We hypothesize that coxsackieviruses may play a permissive role for the perpetuation and possibly the induction of autoimmune disease in pSS.
16595521 Quantitative ultrasonometry of the calcaneus in children with juvenile idiopathic arthriti 2006 Oct OBJECTIVES: To evaluate bone quality by means of quantitative ultrasonometry (QUS) in children with juvenile idiopathic arthritis (JIA). METHODS: Seventy children [37 with oligoarticular JIA, mean age (+/-s.d.) 10.54 +/- 3.42 yr; and 33 with polyarticular rheumatoid factor negative JIA, mean age (+/- s.d.) 11.33 +/- 2.88 yr] were enrolled. Quantitative ultrasonometry was measured on both heels with a Cuba Clinical portable device. Body height, weight and body mass index were recorded together with disease duration and cumulative dose of prednisone. RESULTS: The lowest QUS parameters were observed in children with polyarticular JIA (P< 0.001 and 0.01 when compared with reference data and oligoarticular JIA, respectively). In children with oligoarticular JIA, the QUS values were also significantly lower in comparison with the reference data (P< 0.002). The QUS parameters were strongly influenced by body height, and to a lesser degree by body weight. In children with polyarticular JIA, there were significant inverse correlations between QUS parameters and disease duration [r=-0.57, P< 0.01 for broadband ultrasound attenuation (BUA) and r = - 0.67, P< 0.01 for velocity of sound (VOS)]. Similarly, there were inverse correlations between QUS and cumulative dose of prednisone (r = - 0.48, P< 0.05 for BUA and r =- 0.50, P < 0.01 for VOS, respectively). Similar results were obtained when BUA and VOS were adjusted for height. CONCLUSIONS: Disease duration and cumulative dose of prednisone in children with polyarticular JIA are risk factors of stunted growth and decreased QUS values of bone quality.
16947419 Soluble human p55 and p75 tumor necrosis factor receptors reverse spontaneous arthritis in 2006 Sep OBJECTIVE: The roles of the transmembrane and secreted forms of tumor necrosis factor alpha (TNFalpha) in rheumatoid arthritis (RA) remain unclear. Agents used to inhibit TNFalpha have shown varying efficacy in RA patients, suggesting that anti-TNFalpha agents possess dissimilar mechanisms of action, including the ability to neutralize transmembrane (tmTNFalpha) and secreted TNFalpha. In this study, TNFalpha-knockout (TNFalpha-KO) mice that were genetically altered to express elevated levels of tmTNFalpha were constructed to further understand the roles of the 17-kd secreted, trimeric, and 26-kd transmembrane forms of TNFalpha. METHODS: A speed-congenic mating scheme was used to generate 3 unique strains of mice: 1) transgenic tmTgA86 mice overexpressing 26-kd tmTNFalpha and also secreting 17-kd trimeric TNFalpha (tmTNFalpha-transgenic), 2) TNFalpha-/- mice (TNFalpha-KO), and 3) transgenic mice overexpressing tmTNFalpha backcrossed to TNFalpha-KO mice (tmTNFalpha-transgenic/TNFalpha-KO). Mice were treated with phosphate buffered saline (as vehicle control), dexamethasone (as positive control), or modified recombinant human soluble TNF receptor (sTNFR) p55 or p75, and were assessed clinically and histopathologically for signs of inflammation and development of arthritis. RESULTS: The tmTNFalpha-transgenic/TNFalpha-KO mice were born with crinkled tails and spinal deformities similar to those in ankylosing spondylitis. By 2-4 weeks, these mice developed symmetric inflammatory arthritis, characterized by tissue swelling, pannus formation, and bone deformities. The tmTNFalpha-transgenic mice also developed spontaneous-onset arthritis, but at a slower rate (100% incidence by 10-12 weeks). Clinical and histologic progression of arthritis in the tmTNFalpha-transgenic/TNFalpha-KO mice was reduced by treatment with dexamethasone or with the p55 or p75 sTNFR (69% and 63% reduction in total histologic score, respectively). CONCLUSION: These data show that arthritis is sufficiently initiated and maintained in tmTNFalpha-transgenic/TNFalpha-KO mice, and that it can be neutralized by recombinant human p55 or p75 sTNFR, resulting in amelioration of the biologic and subsequent histologic destructive effects of tmTNFalpha.
16770519 Arthritis in a child secondary to congenital insensitivity to pain and self-aggression. Wh 2007 Jul A 9 year-old female child presented with recurrent arthritis of ankles, left knee and unequal leg length. Clinical examination revealed mild valgus deformity in her left knee with grade 2 effusion, arthritis of both ankles and deformity in her left wrist. Examination of the affected joints showed no evidence of tenderness upon active or passive movements and the patient did not show any limping upon gait analysis. Past history of the patient revealed evidence of previous dislocation of her left hip and previous fibular fracture. Revision of her previous x-rays showed left hip dislocation, fracture left fibula and fracture of right metatarsal bone after repetitive trauma which pass unnoticed. Recent x-ray of her left knee showed osteochondral injury. Laboratory investigations were done to rule out common causes of childhood arthritis and revealed: ESR 12 1st hours, CRP negative, negative rheumatoid factor, and negative ANA. Neurological evaluation of the patient documented congenital insensitivity to pain and EMG studies confirmed evidence of sensory neuropathy. Traumatic arthritis resulting from congenital insensitivity to pain with self-aggression is rarely encountered in children but should be considered in the differential diagnosis specially if radiological features point to repetitive trauma with attempts of healing.
16567388 Neutrophil-derived leukotriene B4 is required for inflammatory arthritis. 2006 Apr 17 Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption.
15778354 Ex vivo characterization of the autoimmune T cell response in the HLA-DR1 mouse model of c 2005 Apr 1 Although the pathogenesis of collagen-induced arthritis (CIA), a model of rheumatoid arthritis, is mediated by both collagen-specific CD4(+) T cells and Ab specific for type II collagen (CII), the role of CII-specific T cells in the pathogenesis of CIA remains unclear. Using tetrameric HLA-DR1 with a covalently bound immunodominant CII peptide, CII(259-273), we studied the development of the CII-specific T cell response in the periphery and arthritic joints of DR1 transgenic mice. Although the maximum number of DR1-CII-tetramer(+) cells was detected in draining lymph nodes 10 days postimmunization, these T cells accounted for only 1% or less of the CD4(+) population. After day 10, their numbers gradually decreased, but were still detectable on day 130. Examination of TCR expression and changes in CD62L, CD44(high), and CD69 expression by these T cells indicated that they expressed a limited TCR-BV repertoire and had clearly undergone activation. RT-PCR analysis of cytokine expression by the tetramer(+) T cells compared with tetramer(-) cells indicated the tetramer(+) cells expressed high levels of Th1 and proinflammatory cytokines, including IL-2, IFN-gamma, IL-6, TNF-alpha, and especially IL-17. Additionally, analysis of the synovium from arthritic paws indicated that the same CD4(+)/BV8(+)/BV14(+)/tetramer(+) T cells were present in the arthritic joints. These data demonstrate that although only small numbers of CII-specific T cells are generated during the development of CIA, these cells express very high levels of cytokine mRNA and appear to preferentially migrate to the arthritic joint, indicating a potential direct role of CII-specific T cells in the pathogenesis of CIA.
16487461 Total ankle arthroplasty with the Agility prosthesis: clinical and radiographic evaluation 2006 Feb BACKGROUND: Although ankle arthrodesis remains a standard operative procedure for disabling ankle arthritis, it has potential long-term problems. Total ankle arthroplasty offers preserved joint motion and may be a more favorable option in select patients. The purpose of this study was to report the intermediate-term clinical and radiographic results of total ankle arthroplasty using the Agility prosthesis. METHODS: We retrospectively reviewed the results of total ankle arthroplasty in 41 consecutive patients (43 ankles). Evaluation included preoperative and postoperative questionnaires, physical examination, and radiographs. RESULTS: At the time of followup, 38 patients (40 ankles) were available for review. The most common preoperative diagnoses included posttraumatic arthritis (24 of 40 ankles, 60%) and rheumatoid arthritis (eight of 40 ankles, 20%). Average age at surgery was 63 (range 32 to 85) years. Average followup was 44.5 (range 26 to 64) months. Preoperative and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scores averaged 33.6 and 83.3, respectively, demonstrating significance (p < 0.001). Postoperative Medical Outcomes Study Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores averaged 49.5 and 56.1, respectively. Although 34 of 40 ankles demonstrated radiographic lucency or lysis, the degree of involvement varied. Migration or subsidence of components was noted in 18 ankles. Overall, 37 of 38 patients were satisfied with the outcome of their surgery and would have the same procedure under similar circumstances. CONCLUSIONS: Agility total ankle arthroplasty results in a favorable clinical outcome and patient satisfaction in most patients at intermediate-term followup. However, total ankle arthroplasty is associated with potential complications and the need for subsequent operative intervention. Radiographic followup commonly reveals periprosthetic lucency, lysis, and component migration or subsidence, but this does not appear to adversely affect the intermediate-term clinical outcome. The long-term consequences of such radiographic findings are of concern, and surgeons and patients choosing this procedure need to be cautious.
16766366 Preferential immunoglobulin oxidation in children with juvenile idiopathic arthritis. 2006 May OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a rare chronic inflammatory disorder of the joints. There is strong evidence that oxidative damage occurs in rheumatoid diseases, including JIA. The increased level of protein oxidation products in total plasma proteins has recently been reported in children with diagnosed JIA. The objective of this study was to find out which fraction of plasma proteins is mostly damaged by oxidative stress and whether the damaging effect correlates with certain clinical or laboratory parameters. METHODS: A new approach to estimate the carbonyl content of plasma protein fractions was developed, based on two-stage electrophoresis and immunochemical detection of the carbonyl derivatives of the proteins. This method allowed us to detect and quantitate carbonyl groups in the albumin, alpha-2, beta and gamma-globulin fractions. Sera of 25 children with JIA and 13 healthy controls were tested. RESULTS: Albumin and gamma-globulins were found to be most modified by oxidation. In a group of children with systemic JIA, both albumin and gamma-globulins were oxidized while plasma gamma-globulin fraction damage was prevalent in pauciarticular JIA. CONCLUSIONS: Among plasma proteins of children with JIA, gamma-globulins were preferentially oxidized, whereas most of the other proteins did not seem to be affected. Oxidative modification of plasma proteins was correlated with the type of JIA. These findings may allow the use of carbonyls as clinical markers of inflammatory process activity in patients with different types of JIA. It is also a potential tool for monitoring oxidative protein damage in other diseases and therapies.
16701134 Distal interphalangeal joint arthrodesis with screw fixation: why and how. 2006 May Though DIP joint fusion can be successfully achieved with K-wires in both the osteoarthritic and rheumatoid patient, their use is often some-what of an inconvenience to the patient. They prohibit showering, may become infected, may back out and catch on clothing, and surely slowdown mobilization of the rest of the finger [1]. For optimal prehension, a modest amount of DIP joint flexion is required, however. Thus, one advantage of K-wires is that they allow fusion in 5 degrees to 10 degrees of flexion (Fig. 1). In the rheumatoid patient in particular, bone stock may be so com-promised that getting enough purchase with wires alone can be challenging. Since making the transition to the Herbert screw, hardware-related complications and patient dissatisfaction with obligatory postoperative functional limitations until union is achieved have been eliminated. Despite the fact that the fusion must occur without flexion-a necessity to ensure intramedullary placement of the screw-patients seem to adapt well (Fig. 2). One further potential disadvantage of screw fixation is the issue of size mismatch between phalanx and screw-especially in the small finger. Though cautious insertion is justified, precise technique allows use even in the small finger-a benefit when early motion is indicated; for example, when concomitant proximal interphalangeal (PIP) implant arthroplasty is performed in an adjacent digit. This device is contraindicated, obviously, if future PIP joint arthro-plasty is anticipated in the same finger (Fig. 3).
16678646 Treatment of psoriatic arthritis with etanercept, methotrexate, and cyclosporin A. 2006 Feb BACKGROUND: Psoriatic arthritis (PsA) is seen in approximately 5% to 42% of individuals with psoriasis. CASE SUMMARY: A 37-year-old white male weighing 90 kg presented with erythrodermic psoriasis and PsA. The overall duration of PsA was 3 years. Serum levels of glucose, electrolytes, and tumor markers were normal, as were the results of tests of hepatic and renal function and urinalysis. The findings of posteroanterior radiographic examination of the chest were also normal. However, radiographic examination showed porosis and degeneration in the lumbar vertebrae; narrowing of the L2-L3, L3-L4, and L5-S1 spaces; degenerative changes and narrowing of the proximal interphalangeal and distal interphalangeal (DIP) joints; and osseous ankylosis of the DIP joints of the hands. The cutaneous eruption improved with cyclosporin A (CsA) 3.5 mg/kg p.o., but the severity of PsA did not change. Therefore, parenteral methotrexate (MTX) 15 mg/wk and an indomethacin suppository 100 mg/d were added to the regimen. CsA and MTX were continued for 3 months, during which the patient's PsA symptoms did not abate, based on tender and swollen joint counts, hand-to-floor distance, erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), antistreptolysin O, and rheumatoid factor. Therefore, etanercept 25 mg s.c. twice weekly was added to the regimen. Three weeks after the initiation of this combination, the patient's arthritis had improved. The visual analog scale score decreased from 9 to 4. Tender and swollen joint counts decreased from 28 and 24 to 15 and 10, respectively. The hand-to-floor distance decreased from 20 to 10 cm. The erythrocyte sedimentation rate and levels of CRP, antistreptolysin O, and rheumatoid factor decreased from 72 mm/h, 162 mg/L, 250 IU/mL, and 304 IU/mL at baseline to 23 mm/h, 64 mg/L, 48 IU/mL, and 56.1 IU/mL, respectively. No change was observed in radiographs of the patient's back, hands, and feet. Based on the American College of Rheumatology scoring system, the patient showed 50% improvement in disease severity. Etanercept was discontinued at the end of 4 weeks, and maintenance therapy was continued with MTX alone. No adverse events were reported during or after the completion of etanercept therapy. CONCLUSION: In this patient with PsA that was refractory to CsA and MTX, either alone or in combination, the severity of PsA was reduced after 4 weeks of the combined use of etanercept, CsA, and MTX.
17029045 Transforming growth factor beta stimulates rheumatoid synovial fibroblasts via the type II 2005 Transforming growth factor (TGF)-beta regulates the function of fibroblasts, and has been shown to have a role in the pathogenesis of rheumatoid arthritis (RA) because several studies have demonstrated the presence of TGF-beta in the synovial tissue and synovial fluids of RA patients. In this study, we examined the expression of TGF-beta receptors in synovial fibroblasts of patients with RA and demonstrated the significance in functional responses of synovial fibroblasts to TGF-beta in this disorder. Transforming growth factor beta1 stimulated the expression of connective tissue growth factor (CTGF) in fibroblasts of patients with RA more than in those of patients with osteoarthritis (OA). Transforming growth factor beta1 induced the chemotactic migration of RA synovial fibroblasts and inhibited their proliferation significantly more than OA synovial fibroblasts. Both RA and OA synovial fibroblasts expressed detectable amounts of TGF-beta receptor type II mRNA, but the expression was higher in RA patients than in OA patients, as assessed by reverse transcriptase-polymerase chain reaction. There was no significant difference in the expression of TGF-beta receptor type I or type III in synovial fibroblasts between RA and OA patients. These results indicate that synovial fibroblasts of RA patients express the increased TGF-beta receptor type II, which is associated with altered responses to TGF-beta observed in CTGF expression, chemotaxis, and proliferation of RA synovial fibroblasts, and may have an important role in the pathogenesis of RA.
17207391 Molecular mechanisms in normal pregnancy and rheumatic diseases. 2006 Nov Pregnancy is a phenomenon that is not totally understood, based on the complex molecular interactions between the mother and the embrio. Once the fecundation is completed the fetus starts to fight for survival. The first challenge is the implantation process and the second one is the interaction with the maternal immune system. This review discusses how the fetus avoids the immune system rejection, and the mechanisms that the maternal immune system adapts in order to be fit for a successful pregnancy. Also, we focus in this paper on the effects of pregnancy in rheumatic diseases, because the myriad clinical outcomes of the disease itself and the obstetric complications dependent of the disease implicated, as for example in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropaties and antiphospholipid syndrome (APS).