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ID PMID Title PublicationDate abstract
12412193 Subtyping of osteoarthritic synoviopathy. 2002 Sep OBJECTIVE: Osteoarthritis research is traditionally concentrating on events within the degenerated articular cartilage. Changes in the synovial membrane are largely neglected. In fact, they are generally interpreted as secondary to the cartilage changes and not pathogenetically involved in the disease process. In this study, we present a systematic analysis of the synovial reaction pattern in early and late stages of the osteoarthritic disease process. METHODS: A large series of synovial specimens derived from early and late stage osteoarthritic cartilage disease were investigated by histological and immunohistochemical means for tissue architecture and inflammatory cell infiltrates. For comparison, also samples with rheumatoid arthritis, seronegative arthritis, and septic arthritis were included as well as normal synovial membrane specimens. RESULTS: In all specimens derived from patients with diagnosed osteoarthritis alterations of the synovial tissue were observed. A large spectrum of alterations was found in different stages of osteoarthritic joint disease and four different basic pattern of synovial reactions could be identified: (i) hyperplastic, (ii) inflammatory, (iii) fibrotic, and (iv) detritus-rich synoviopathy. CONCLUSION: We show that in all cases of clinically overt osteoarthritic joint disease significant synovial pathology is associated. Furthermore, our study clearly documents that in osteoarthritic synovium significant inflammation can occur. This is suggestive of a distinct pathogenetic role of the synovium also in osteoarthritic cartilage degeneration at least in a subset of cases.
12396227 Management of spondyloarthropathy: new pharmacological treatment options. 2002 Spondyloarthropathies (SpA) are a group of inflammatory arthritides classified according to common features of peripheral and spinal arthritis. The conventional anti-inflammatory and disease-modifying or slow-acting anti-rheumatic drugs do appear to be efficacious in treatment of the peripheral arthritis in a comparable fashion to seropositive rheumatoid arthritis, however, their efficacy in axial disease is unproven. This review examines new pharmacological developments in the treatment of SpA including the specific features of sacroiliitis, enthesitis and spondylitis in addition to the peripheral manifestations. The main points that are discussed are new cyclo-oxygenase (COX)-2 specific anti-inflammatories, biological therapies, such as anti-TNF compounds, and novel uses of well-known agents.
12235554 [Imaging in rheumatology]. 2002 Sep 13 Conventional radiography, ultrasonography, scintigraphy, computed tomography, and magnetic resonance imaging (MRI) are important diagnostic tools in rheumatology additional to clinical investigation. Radiography provides information both of the juxtaarticular and the abarticular bone. It is relevant in the diagnosis of rheumatoid arthritis, osteoarthritis, spondylarthropathies, and osteoporosis, and for the investigation of other regions like the thorax. Sonography is superior to radiography to delineate soft tissue structures such as effusions, tenosynovitis, tendinitis, paratendinitis, bursitis, and soft-tissue tumors, but also to evaluate bone surfaces. It helps to perform injections and punctures. Furthermore it is a new diagnostic tool for the diagnosis of temporal arteritis, Takayasu's arteritis, and Sjögren's syndrome. Echocardiography, abdominal and pleural sonography are also frequently used. MRI is useful to detect soft tissue lesions and bone lesions. It is helpful to depict synovial membrane, tendon, tendon sheaths, ligaments, cartilage, destructive joint processes, and rupture of synovial cysts. MRI is an established imaging technique in diagnosis of sacroiliitis and cervical arthritis as well as in diagnosis of osteonecrosis. It is an important diagnostic modality for demonstrating early arthritis. MRI is also of interest in diagnosis of neurological disorders of connective tissue diseases or vasculitis in rheumatology. Bone scintigraphy is an established imaging technique in diagnosis of skeletal diseases as well as in diagnosis of tumors. "Hot spots" are seen in locations of high bone turn over. Scintigraphy is also helpful to localize or exclude inflammation.
15345502 Preliminary results of safety and efficacy of the interleukin 1 receptor antagonist anakin 2005 Apr BACKGROUND: Joint involvement occurs in most patients with systemic lupus erythematosus (SLE), and severe lupus arthritis is often refractory to conventional treatments. Anakinra is used in the treatment of rheumatoid arthritis, but its therapeutic potential has not been proved in patients with SLE. OBJECTIVE: To determine the safety/tolerability and efficacy of anakinra in patients with SLE with leading joint involvement. METHODS: In patients with SLE with active polyarthritis and no other uncontrolled systemic/organ manifestations, 100 mg/day anakinra was self administered subcutaneously for 3 months. Disease activity was assessed by VAS, number of swollen/tender joints, ECLAM score, and serological and immunological measures. RESULTS: Four patients with SLE were studied; anakinra was safe in all four patients and no drug related serious adverse events occurred. A subjective benefit was seen in all patients and a trend towards better activity measures after 4 weeks. After an initial response, one patient left the study because of an arthritic flare after 6 weeks. CONCLUSION: In this study anakinra was apparently safe and well tolerated and led to clinical and serological improvement. Anakinra might be an interesting alternative in individual patients with lupus arthritis not responding to conventional treatments.
11987936 What are the advances for surgical therapy of inflammatory diseases of the spine? 2002 Jan Surgery for rheumatoid arthritis (RA) and spondyloarthropathies is a palliative surgery, and testifies to the failure of conservative treatment. In RA, surgery is generally used to deal with upper cervical instability and peridens pannus compression. These complications can have dramatic neurological consequences and can even be life threatening. Every effort must be made to avoid unnecessary surgery but, if needed, the indication must be precise and timely to be efficient. Instrumented fusion is indicated but the need for pannus excision is discussed. In ankylosing spondylitis (AS), major deformity will be the indication for corrective surgery if this deformity induces a marked decrease in the field of vision, thoracicy or abdominal problems or respiratory and mandibular troubles in the cervical spine. Different types of osteotomies with instrumented fixation are described. In AS. surgery is also indicated in fractures that are potentially unstable. At the cervical level these fractures are a surgical emergency. Neurological compressions and spondylodiscitis are other reasons for surgery in AS. Complications of other spondyloarthropathies, which include accompanying psoriasis, reactive arthritis, enteropathic arthritis or Behcet's syndrome are occasionally treated surgically along the same lines as RA or AS. Surgery for spinal inflammatory disorders involves major procedures with a high rate of severe complications. The indications for this type of surgery must be extremely precise and both the surgeon's and the patient's expectations must be clear and realistic. The surgery should only be performed by a surgeon who is experienced with this type of patient and procedure but, furthermore, it should also only be camed out in a centre with a team of neurologists, anaesthetists, nurses and physical therapists who have the expertise to work with these pathologies and these often severely debilitated patients. Only under these conditions will the outcome justify the burden and the risks.
12461081 Essential role for the C5a receptor in regulating the effector phase of synovial infiltrat 2002 Dec 2 A characteristic feature of rheumatoid arthritis is the abundance of inflammatory cells in the diseased joint. Two major components of this infiltrate are neutrophils in the synovial fluid and macrophages in the synovial tissue. These cells produce cytokines including tumor necrosis factor alpha and other proinflammatory mediators that likely drive the disease through its effector phases. To investigate what mechanisms underlie the recruitment of these cells into the synovial fluid and tissue, we performed expression analyses of chemoattractant receptors in a related family that includes the anaphylatoxin receptors and the formyl-MetLeuPhe receptor. We then examined the effect of targeted disruption of two abundantly expressed chemoattractant receptors, the receptors for C3a and C5a, on arthritogenesis in a mouse model of disease. We report that genetic ablation of C5a receptor expression completely protects mice from arthritis.
12439246 Cementless total knee arthroplasty in patients 50 years or younger. 2002 Nov Total knee arthroplasty now is being advocated for use in younger patients with posttraumatic and rheumatoid arthritis. Advances in technology, design, and materials potentially have allowed for more predictable results. There has been continued interest in cementless fixation for use in younger patients. Between 1986 and 1998, 75 total knee replacements in 57 patients 50 years or younger were done. All surgeries were done by one surgeon (AAH). There were 35 left knees and 40 right knees. The average age of the patients was 42 years (range, 31-50 years). Followup averaged 111 months. Preoperative range of motion was 5 degrees to 106 degrees and postoperative range of motion was 2 degrees to 113 degrees. Modified Hospital for Special Surgery knee scores improved from an average of 67 points preoperatively to an average of 97 points postoperatively. The majority of the diagnoses were posttraumatic arthritis or osteoarthritis (57%), indicating a young, active group of patients. There were two infections and 12 polyethylene exchanges. There were no revisions for loosening or implant failure. There was a correlation between prior knee surgeries and the need for a manipulation. Radiographically, there were no loose implants. Cementless fixation in the young patient with high physical demands was clinically reliable.
12916786 Performance of rapid malaria Pf antigen test for the diagnosis of malaria and false-reacti 2003 Recently introduced rapid nonmicroscopic immunocapture assays for the diagnosis of malaria infection are being evaluated for their sensitivity and specificity in various epidemiological settings. A Plasmodium falciparum histidine-rich protein-2 (PfHRP-2)-based assay (ICT malaria Pf assay) was evaluated for its performance and compared to that of Giemsa-stained thick blood film microscopy. Of the 515 patients tested, 163 were positive for malaria parasites on thick blood film microscopy: 87 were infected with P. vivax; 63 with P. falciparum; 1 with P. malariae; and 12 with both P. falciparum and P. vivax. The ICT assay detected 53 P. falciparum infections and, as expected, failed to detect all but one case of P. vivax. Three cases of mixed infections were also not detected by this assay. The performance of the ICT assay in diagnosing P. falciparum infection was comparable to that of microscopy. The sensitivity of the ICT assay was 82% and the specificity 99.0%. The ICT assay also detected 4 false-positive cases. These patients reported treatment with chloroquine in the previous 2-5 weeks. The specificity of the assay was evaluated in different groups of patients, who had tested negative for malaria infection by microscopy. These patients were selected from different disease groups: rheumatoid arthritis; hepatitis C; toxoplasmosis; schistosomiasis; and hydatid disease. Of the 225 patients studied, 133 were positive for rheumatoid factor. Thirty-five (26%) of the 133 patients had false positive-reactions with the ICT assay, while only four had false positive-reactions with the OptiMAL test. After the rheumatoid factor was absorbed 33 of the 35 false-positive specimens were negative when retested with the ICT assay. Our study shows that the PfHRP-2-based ICT assay gave a false positive-reaction in 26% of the patients who had rheumatoid factors, but were negative for malaria by microscopy. We conclude that new rapid nonmicroscopic methods for the diagnosis of malaria that complement or support blood film microscopy would be of great use in the diagnosis and treatment of patients with malaria and also in epidemiological studies.
15132522 How do patients with rheumatic disease experience their relationship with their doctors? A 2004 Feb This study is evaluated what patients with rheumatic disease perceive as important in their medical encounters. We interviewed two groups of patients: one with a well-defined inflammatory condition (rheumatoid arthritis (RA) or ankylosing spondylitis) (n = 12) and one with non-inflammatory widespread chronic pain such as fibromyalgia (n = 14). Both groups focused on their relationship to their doctor. Two central themes emerged as of importance: 'to be seen' and 'to be believed'. However, these themes had different connotations for the two groups. For the patients with inflammatory conditions, 'to be seen' implied being seen as an individual and not as a mere diagnosis, and 'to be believed' as far as pain and suffering were concerned. For patients with non-inflammatory chronic pain 'to be seen' and 'to be believed' primarily implied being able to obtain a useful somatic diagnosis. Practical implications of these findings are discussed.
12011370 Possible contribution of microchimerism to the pathogenesis of Sjögren's syndrome. 2002 May OBJECTIVES: Microchimerism of foetal cells occurs during most pregnancies. Two autoimmune diseases, systemic sclerosis (SSc) and Sjögren's syndrome (SS), have many clinical and pathological similarities to chronic graft-vs-host disease (GVHD). These findings suggest that anti-maternal graft-vs-host reaction by foetal cells may be involved in the pathogenesis of the diseases. To explore this hypothesis, we examined foetal DNA in peripheral blood of 59 women and in salivary glands from 28 women. METHODS: DNA extracted from peripheral blood and the affected minor salivary glands was analysed for the Y-chromosome-specific gene using a nested polymerase chain reaction (PCR) test. In the minor salivary gland specimens, the Y-chromosome-positive foetal cells were identified by in situ hybridization with a Y-chromosome-specific DNA probe. RESULTS: In peripheral blood, there was no significant difference between controls and patients with SSc or SS. In salivary glands, foetal DNA was detected in 11 of 20 women with SS but in only one of eight normal controls using PCR test. Additionally, foetal cells were clearly detected in three out of eight women with SS by the use of in situ hybridization. CONCLUSIONS: The identification of foetal cells in salivary glands suggests that anti-maternal GVHD may be involved in the development of SS.
12645111 [A case of adult-onset Still's disease complicated with acute respiratory distress syndrom 2002 Nov A 24-year-old woman was admitted to our hospital because of a high fever that had persisted for two weeks. She complained of a sore throat and arthralgia, and had evanescent rash, lymphadenopathy, liver dysfunction, and hyperferritinemia. Tests for RF and ANA were negative. Adult-onset Still's disease was diagnosed. On the fifth day of hospitalization, acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) developed. Treatment consisted of mechanical ventilation and administration of steroid pulse-therapy and gabexate mesilate. Analysis of fluid obtained by bronchoalveolar lavage showed increases in the total cell count, predominantly of neutrophils and lymphocytes. Bilateral pulmonary infiltration seen on chest radiographs was alleviated, and the arterial blood gas data gradually improved. After cyclosporine was given, all the above symptoms associated with adult-onset Still's disease disappeared. Plasma levels of inflammatory cytokines decreased with the improvement of the patient's clinical condition.
12053528 [Multiple urinary lithiasis and nephrocalcinosis secondary to primary Sjögren syndrome]. 2002 Mar A 39 year old women with a primary Sjögren syndrome (pSS) had bilateral and multiple nephrolithiasis and nephrocalcinosis due to distal renal tubular acidosis (dRTA), hypercalciuria and hypocitraturia. She had in serum positive antinuclear antibodies with mottled pattern 1/320, totals ENA, Anti-SSA/Ro 52, Anti-SSA/Ro 60 and Anti-SSB-La antibodies. Stones were removed with extracorporeal shock wave lithotripsy satisfactory and were composed of calcium phosphate and calcium oxalate. Metabolic abnormalities were resolved with potassium citrate and hydrochlorothiazide. At two years of follow-up, the patient hadn't stone recurrence and had normal 24-hour urinary levels of citrate and calcium.
15485632 A T cell intrinsic role of Id3 in a mouse model for primary Sjogren's syndrome. 2004 Oct Sjogren's syndrome is an autoimmune disease with clinical hallmarks of keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth). The genetic basis of this autoimmune disease is poorly understood. Id3 is an immediate early-response gene in growth regulation and is involved in TCR-mediated T cell selection during T cell development. Here, we show that Id3-deficient mice develop many disease symptoms found in primary Sjogren's syndrome patients including dry eyes and mouth, lymphocyte infiltration in lachrymal and salivary glands, and development of anti-Ro and anti-La antibodies. Adoptive transfer experiment indicated a T cell intrinsic role for Id3 in the development of Sjogren's symptoms. Furthermore, genetic ablation of T cells or neonatal 3 day thymectomy in Id3-deficient mice showed a rescue of disease symptoms, suggesting a thymic origin of autoimmune T cells. Thus, this study establishes a critical connection between Id3-mediated T cell development and autoimmune diseases.
12059992 Enhanced DNA damage-induced p53 peptide phosphorylation and cell-cycle arrest in Sjögren' 2002 Jun BACKGROUND: Cells from primary Sjögren's syndrome (SS) patients have been reported to show alterations in DNA repair and p53 expression. The DNA-dependent protein kinase (DNA-PK) autoantigen may be involved in both of these alterations in relation to cellular DNA damage responses. We conducted this study of cell-cycle kinetics and p53 to find additional evidence for an abnormal stress response role in the pathogenesis of SS. DESIGN: DNA-dependent protein kinase activity, p53 peptide phosphorylation and p53 protein levels were determined in gamma-irradiated long-term T lymphocyte cultures. Cell-cycle progression of peripheral blood mononuclear cells was analysed with flow cytometry. RESULTS: No significant differences in the DNA-PK activities or p53 protein levels appeared between the SS patients and the healthy individuals. However, patients with the SS hallmark Ro/SS-A and La/SS-B autoantibodies showed enhancement of both p53 peptide phosphorylation (P = 0.036) and G1 cell-cycle arrest (P = 0.015) in response to gamma radiation. CONCLUSIONS: Sjögren's syndrome cells express an enhanced G1 checkpoint function which may be mediated partly by p53 phosphorylation, suggesting that an abnormal stress response in SS is of relevance for the development of this autoimmune disease.
12355497 Lectin-like oxidized low-density lipoprotein receptor 1 mediates leukocyte infiltration an 2002 Sep OBJECTIVE: The relationship between rheumatoid arthritis and atherosclerosis has been recognized for >20 years. This study aimed to elucidate the roles of oxidized low-density lipoprotein (ox-LDL; one of the main pathogenic factors of atherosclerosis) and its endothelial receptor, lectin-like ox-LDL receptor 1 (LOX-1), in arthritic joints using a rat zymosan-induced arthritis (ZIA) model. METHODS: LOX-1 expression and ox-LDL accumulation in arthritic joints were detected by immunohistochemistry using specific mouse anti-LOX-1 and anti-ox-LDL monoclonal antibodies, respectively. To elucidate the effects of the expressed LOX-1 on arthritis, ZIA rats were treated with anti-LOX-1 antibody or normal mouse IgG. The severity of arthritis was analyzed by joint swelling. Cell infiltration, synovial hyperplasia, and proteoglycan losses were also determined by histologic scoring. Proinflammatory cytokine and nitrite levels in serum and joint fluid were also measured. RESULTS: Immunohistochemical study of ZIA demonstrated LOX-1 expression on synovial endothelium and postcapillary venules at 6 hours after the induction of inflammation, with maximum expression detected at 24 hours. LOX-1 was also expressed weakly on both joint cartilage and synovium. Ox-LDL, a ligand of LOX-1, was also detected in articular chondrocytes. Administration of anti-LOX-1 antibody, which blocks LOX-1 activity, suppressed joint swelling (by 33.5%), leukocyte infiltration, and joint nitrite accumulation at 24 hours, as well as cartilage destruction at 7 days, compared with control rats. CONCLUSION: LOX-1 induction in arthritic joints might play a role in promoting joint inflammation and cartilage destruction by mediating leukocyte infiltration into the arthritic joints of ZIA rats.
12355496 Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced 2002 Sep OBJECTIVE: To determine if the new, orally active C5a receptor antagonist, the cyclic peptide AcF-[OPdChaWR], reduces the severity of pathology in a rat model of immune-mediated monarticular arthritis. METHODS: Arthritis was induced in the right knee of previously sensitized rats by the intraarticular injection of methylated bovine serum albumin. Rats were examined for either 14 days or 28 days, or for 49 days following a second antigen challenge at 28 days. The C5a antagonist (1 or 3 mg/kg/day) and/or ibuprofen (30 mg/kg/day) were administered orally on a daily basis either before or after arthritis induction. RESULTS: Rats receiving AcF-[OPdChaWR] had significant reductions in right knee swelling, gait disturbance, lavaged joint cell numbers, and right knee histopathology, as well as in serum levels of tumor necrosis factor alpha (TNFalpha) and intraarticular levels of interleukin-6 and TNFalpha on day 14. In the 14- and 28-day studies, ibuprofen resulted in a similar reduction in gait abnormalities and intraarticular inflammatory cells compared with the C5a antagonist, but was less effective in reducing knee swelling over the course of the study and had no effect on knee histopathology. Combination therapy with AcF-[OPdChaWR] and ibuprofen resulted in no greater efficacy than with the C5a antagonist alone. Rats injected twice with the antigen in the 49-day study displayed the most severe histopathology and this, as well as knee swelling and gait abnormalities, was significantly reduced by repeated treatment with the C5a antagonist. CONCLUSION: An agent that inhibits the action of C5a in this model significantly reduced joint pathology, while ibuprofen was not effective. C5a antagonists could therefore have broader therapeutic benefits than nonsteroidal antiinflammatory drugs as antiarthritic agents for rheumatoid arthritis.
15590764 Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve saliva 2005 Apr OBJECTIVE: To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjogren's syndrome (pSS), (ii) increased levels of cholinesterase of lymphocyte origin could interfere with the secretory activity of submandibular acinar cells, and (iii) hydroxychloroquine at therapeutic doses could interfere with cholinesterase activity. METHODS: The Ellman method was used to determine the levels of salivary cholinesterase activity and the K(i) of both chloroquine and hydroxychloroquine for serum cholinesterase. The ability of lymphocyte cholinesterase to inhibit the acetylcholine (ACh)-evoked rise in [Ca(2+)](i) in mouse submandibular acinar cells was determined using fura-2 microfluorimetry. RESULTS: Patients with pSS had significantly higher levels of cholinesterase activity in both their unstimulated (P < 0.05) and stimulated saliva (P < 0.0001) compared with control subjects. Lymphocyte cholinesterase was capable of inhibiting the ACh-evoked rise in [Ca(2+)](i). The in vitro K(i) for hydroxychloroquine inhibition of cholinesterase was 0.38 +/- 1.4 microM. CONCLUSION: These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed.
12475001 Pregnancy outcome in 100 women with autoimmune diseases and anti-Ro/SSA antibodies: a pros 2002 Anti-Ro/SSA antibodies are associated with neonatal lupus but are also considered a possible cause for unexplained pregnancy loss and adverse pregnancy outcome. In a large multicentres cohort study we have prospectively followed 100 anti-Ro/SSA positive women (53 systemic lupus erythematosus (SLE)) during their 122 pregnancies and 107 anti-Ro/SSA negative women (58 SLE) (140 pregnancies). Anti-Ro/SSA antibodies were tested by immunoblot and counterimunoelectrophoresis. Mean gestational age at delivery (38 vs 37.9 weeks), prevalence of pregnancy loss (9.9 vs 18.6%), preterm birth (21.3 vs 13.9%), cesarean sections (49.2 vs 53.4%), premature rupture of membranes (4.9 vs 8.1%), preeclampsia (6.6 vs 8%), intrauterine growth retardation (0 vs 2.3%)and newborns small for gestational age (11.5 vs 5.8%) were similar in anti-Ro/SSA positive and negative SLE mothers; findings were similar in non-SLE women. Two cases of congenital heart block were observed out of 100 anti-Ro/SSA positive women. In conclusion, anti-Ro/SSA antibodies are responsible for congenital heart block but do not affect other pregnancy outcomes, both in SLE and in non-SLE women. The general outcome of these pregnancies is now very good, ifprospectively followed by multidisciplinary teams with ample experience in this field.
12410795 Subcellular redistribution and surface exposure of the Ro52, Ro60 and La48 autoantigens du 2002 Nov The Ro52, Ro60 and La48 autoantigens are associated with Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The mechanisms behind tolerance breakdown of these self-peptides remain unclear; however, apoptosis has been proposed to cause their presentation to the immune system. We have examined the localization of transiently expressed enhanced green fluorescent protein (EGFP)-tagged Ro52, Ro60 and La48 autoantigens in a human salivary gland (HSG) cell line by laser confocal microscopy under normal growth conditions and during apoptosis. Surface exposure of Ro52, Ro60 and La48 was demonstrated on nonfixed apoptotic cells with monoclonal antibodies (MoAbs) or with primary SS patient antisera. Laser scanning cytometry determined the apoptotic frequency. EGFP alone was studied as control. We found that Ro52 mainly is cytoplasmic, Ro60 both nuclear and cytoplasmic, while La48 only resides in the nucleus under normal conditions. During early apoptosis, La48 is dramatically redistributed to the cytoplasm, while the localization of Ro52 and Ro60 is maintained. All three autoantigens filled apoptotic blebs and covered TUNEL (terminal-deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling)-positive apoptotic bodies. Identical results were obtained in COS-7 cells. We have developed a transfection system to study the intracellular localization of the three autoantigens Ro52, Ro60 and La48, without antibody detection. During apoptosis, there is an intracellular redistribution of endogenous and EGFP-tagged Ro52, Ro60 and La48, leading to surface exposure. These findings may indicate a role for apoptosis in the induction and facilitation of humoral responses to Ro52, Ro60 and La48 in the autoimmune exocrinopathy of SS.
15248234 Zoledronic acid protects against local and systemic bone loss in tumor necrosis factor-med 2004 Jul OBJECTIVE: Increased osteoclast activity is a key factor in bone loss in rheumatoid arthritis (RA). This suggests that osteoclast-targeted therapies could effectively prevent skeletal damage in patients with RA. Zoledronic acid (ZA) is one of the most potent agents for blocking osteoclast function. We therefore investigated whether ZA can inhibit the bone loss associated with chronic inflammatory conditions. METHODS: Human tumor necrosis factor (TNF)-transgenic (hTNFtg) mice, which develop severe destructive arthritis as well as osteoporosis, were treated with phosphate buffered saline, single or repeated doses of ZA, calcitonin, or anti-TNF, at the onset of arthritis. RESULTS: Synovial inflammation was not affected by ZA. In contrast, bone erosion was retarded by a single dose of ZA (-60%) and was almost completely blocked by repeated administration of ZA (-95%). Cartilage damage was partly inhibited, and synovial osteoclast counts were significantly reduced with ZA treatment. Systemic bone mass dramatically increased in hTNFtg mice after administration of ZA, which was attributable to an increase in trabecular number and connectivity. In addition, bone resorption parameters were significantly lowered after administration of ZA. Calcitonin had no effect on synovial inflammation, bone erosion, cartilage damage, or systemic bone mass. Anti-TNF entirely blocked synovial inflammation, bone erosion, synovial osteoclast formation, and cartilage damage but had only minor effects on systemic bone mass. CONCLUSION: ZA appears to be an effective tool for protecting bone from arthritic damage. In addition to their role in antiinflammatory drug therapy, modern bisphosphonates are promising candidates for maintaining joint integrity and reversing systemic bone loss in patients with arthritis.