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ID PMID Title PublicationDate abstract
19035490 Increased number and function of FoxP3 regulatory T cells during experimental arthritis. 2008 Dec OBJECTIVE: CD4+CD25+FoxP3+ regulatory T (Treg) cells are critical regulators of autoimmunity. Yet the number of Treg cells is paradoxically increased in rheumatoid arthritis (RA) patients, and Treg cells show variable activity in human studies. The objective of this study was to characterize the expansion and function of Treg cells during the initiation and progression of experimental arthritis. METHODS: To unequivocally identify Treg cells, we crossed FoxP3gfp mice with K/BxN mice to generate arthritic mice in which Treg cells express green fluorescence protein. We examined the expansion and function of Treg cells and effector T (Teff) cells during different stages of arthritis, using flow cytometry and cell proliferation analyses. RESULTS: In K/BxN mice, thymic selection of KRN T cells resulted in an enrichment of forkhead box P3 (FoxP3)-positive Treg cells. Treg cell numbers increased during arthritis, with significant increases in spleens and draining lymph nodes, indicating selective tropism to sites of disease. In contrast to the in vitro unresponsiveness of Treg cells when cultured alone, substantial proportions of Treg cells proliferated in both nonarthritic and arthritic mice. However, they also underwent greater apoptosis, thereby maintaining equilibrium with Teff cells. Similarly, enhanced Treg cell-suppressive activity during arthritis was offset by greater resistance by their Teff cell counterparts and antigen-presenting cells. CONCLUSION: In this well-established model of RA, the interplay of Teff cells and Treg cells in K/BxN mice recapitulated many features of the human disease. We demonstrated an ordered expansion of Treg cells during arthritis and dynamic changes in Treg cell and Teff cell functions. By elucidating factors that govern Treg cell and Teff cell development in K/BxN(gfp) mice, we will gain insight into the pathophysiology of and develop novel therapeutics for human RA.
17656469 Pharmacokinetics and pharmacodynamics of DPC 333 ((2R)-2-((3R)-3-amino-3{4-[2-methyl-4-qui 2007 Oct DPC 333 ((2R)-2-((3R)-3-amino-3{4-[2-methyl-4-quinolinyl) methoxy] phenyl}-2-oxopyrrolidinyl)-N-hydroxy-4-methylpentanamide)) is a potent and selective inhibitor of tumor necrosis factor (TNF)-alpha-converting enzyme (TACE). It significantly inhibits lipopolysaccharide-induced soluble TNF-alpha production in blood from rodents, chimpanzee, and human, with IC(50) values ranging from 17 to 100 nM. In rodent models of endotoxemia, DPC 333 inhibited the production of TNF-alpha in a dose-dependent manner, with an oral ED(50) ranging from 1.1 to 6.1 mg/kg. Oral dosing of DPC 333 at 5.5 mg/kg daily for 2 weeks in a rat collagen antibody-induced arthritis model suppressed the maximal response by approximately 50%. DPC 333 was distributed widely to tissues including the synovium, the site of action for antiarthritic drugs. Pharmacokinetic and pharmacodynamic studies in chimpanzee revealed a systemic clearance of 0.4 l/h/kg, a V(ss) of 0.6 l/kg, an oral bioavailability of 17%, and an ex vivo IC(50) for the suppression of TNF-alpha production of 55 nM (n = 1). In a phase I clinical trial with male volunteers after single escalating doses of oral DPC 333, the terminal half-life was between 3 and 6 h and the ex vivo IC(50) for suppressing TNF-alpha production was 113 nM. Measurement of the suppression of TNF-alpha production ex vivo may serve as a good biomarker in evaluating the therapeutic efficacy of TACE inhibitors. Overall, the pharmacological profiles of DPC 333 support the notion that suppression of TNF-alpha with TACE inhibitors like DPC 333 may provide a novel approach in the treatment of various inflammatory diseases including rheumatoid arthritis, via control of excessive TNF-alpha production.
28178484 An Endogenous TNF-α Antagonist Induced by Splice-switching Oligonucleotides Reduces Infla 2008 Jul Tumor necrosis factor-α (TNF-α) is a key mediator of inflammatory diseases, including rheumatoid arthritis (RA), and anti-TNF-α drugs such as etanercept are effective treatments. Splice-switching oligonucleotides (SSOs) are a new class of drugs designed to induce therapeutically favorable splice variants of targeted genes. In this work, we used locked nucleic acid (LNA)-based SSOs to modulate splicing of TNF receptor 2 (TNFR2) pre-mRNA. The SSO induced skipping of TNFR2 exon 7, which codes the transmembrane domain (TM), switching endogenous expression from the membrane-bound, functional form to a soluble, secreted form (Δ7TNFR2). This decoy receptor protein accumulated in the circulation of treated mice, antagonized TNF-α, and altered disease in two mouse models: TNF-α-induced hepatitis and collagen-induced arthritis (CIA). This is the first report of upregulation of the endogenous, circulating TNF-α antagonist by oligonucleotide-induced splicing modulation.
16882875 Z39Ig is expressed on macrophages and may mediate inflammatory reactions in arthritis and 2006 Oct Z39Ig is a transmembrane protein containing two Ig homology domains with unknown functions. Immunohistochemical analyses of human carotid atherosclerotic plaques detected Z39Ig staining in areas rich in foamy macrophages. Z39Ig staining was also observed in macrophages in the lining layers and sublining areas of rheumatoid arthritis synovium. Z39Ig staining in the osteoarthritis synovium was restricted to macrophages in the lining layers. To identify the role(s) of Z39Ig in the function of macrophages, we used human monocytic cell lines TF-1A (Z39Ig-negative) and THP-1 (Z39Ig-positive). The expression of Z39Ig was induced in TF-1A cells ,when they were differentiated into macrophages by treatment with PMA. The stimulation of PMA-treated TF-1A or THP-1 cells with immobilized anti-Z39Ig mAb induced the secretion of IL-8 and matrix metalloproteinase (MMP)-9, which was dependent on NF-kappaB activation. These data indicate that the macrophage Z39Ig is involved in the pathogenesis of inflammatory diseases through chemokine induction, which will promote the migration of inflammatory cells into the lesion area, and MMP-9 induction, which will contribute to cartilage destruction or extracellular matrix degradation.
18971286 LPS activation is required for migratory activity and antigen presentation by tolerogenic 2009 Feb Autoimmune pathologies are caused by a breakdown in self-tolerance. Tolerogenic dendritic cells (tolDC) are a promising immunotherapeutic tool for restoring self-tolerance in an antigen-specific manner. Studies about tolDC have focused largely on generating stable maturation-resistant DC, but few have fully addressed questions about the antigen-presenting and migratory capacities of these cells, prerequisites for successful immunotherapy. Here, we investigated whether human tolDC, generated with dexamethasone and the active form of vitamin D3, maintained their tolerogenic function upon activation with LPS (LPS-tolDC), while acquiring the ability to present exogenous autoantigen and to migrate in response to the CCR7 ligand CCL19. LPS activation led to important changes in the tolDC phenotype and function. LPS-tolDC, but not tolDC, expressed the chemokine receptor CCR7 and migrated in response to CCL19. Furthermore, LPS-tolDC were superior to tolDC in their ability to present type II collagen, a candidate autoantigen in rheumatoid arthritis. tolDC and LPS-tolDC had low stimulatory capacity for allogeneic, naïve T cells and skewed T cell polarization toward an anti-inflammatory phenotype, although LPS-tolDC induced significantly higher levels of IL-10 production by T cells. Our finding that LPS activation is essential for inducing migratory and antigen-presenting activity in tolDC is important for optimizing their therapeutic potential.
19075965 Infectious complications with anti-TNFalpha therapy in rheumatic diseases: a review. 2007 Feb TNFalpha plays a pivotal role not only in the inflammatory process but also in the normal response against pathogens and therefore, interfering with this cytokine may increase the risk of infection. TNFalpha antagonists are commonly used in daily clinical practice for the treatment of inflammatory rheumatic diseases including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis since the beginning of 2000. The spectrum of pathogens giving infectious disease in patients under anti-TNFalpha therapies ranges from common bacteria to more opportunistic organisms such as Mycobacterium tuberculosis. The infections which were described with TNFalpha inhibitors may have a benign course or may be a serious, life threatening disease, and may be localized or disseminated. These TNFalpha inhibitors related infections were described in the randomized clinical trials, and were then declared to post-marketing surveillance systems and special registries. Tuberculosis (TB) is the most frequent opportunistic infection which has been reported with TNFalpha antagonists and the highest risk appears to be associated with infliximab, and at a lesser extent with etanercept. Currently available data and recent patents on the risk of TB with adalimumab are not sufficient to conclude, but TB cases were also reported with this agent. The description of TB infections with TNFalpha inhibitors led to the establishment of new guidelines for screening patients at high risk of developing TB. These data highlight the importance of post-marketing surveillance and special registries for accurately evaluating the safety profile and particularly the infectious risk of this very effective class of drug in inflammatory rheumatic diseases.
19032811 Rheumatic manifestations in HIV-1 infected in-patients and literature review. 2008 Sep OBJECTIVE: To report the rate and spectrum of the rheumatic manifestations of human immunodeficiency virus (HIV) since the advent of highly active anti-retroviral therapy (HAART). METHODS: A retrospective record review of 888 inpatients with HIV for rheumatic manifestations was performed from January 1995 to March 2006. We then searched the 888 records for rheumatic diseases using International Classification Diagnostic (ICD) Codes. The medical records of the cases of HIV with the rheumatic conditions were then reviewed. A computer-assisted search of Medline/Pubmed for the medical literature from January 1981 to August 2007 using the keywords HIV, acquired immune-deficiency syndrome, rheumatic manifestations, combining with text words like systemic lupus erythematosus (SLE). Only English language literature was included. RESULTS: The demographic data of 888 cases of HIV included men (64%) and women (36%) with a mean age of 41.5+/-10.2 years. Race consisted of Black (70%), White (22.8%), Hispanic (6.5%), and others (1.1%). Rheumatic manifestations were present in 80 (9%) with arthritis/arthralgia 49 (5.5%), septic arthritis 9 (1%), and osteomyelitis 8 (0.9%), connective tissue diseases (CTDs) 6 (0.7%) (SLE 3, rheumatoid arthritis 1, polymyositis 1, and systemic sclerosis 1), avascular necrosis 6 (0.7%) (hips 3, knees 2, and shoulder 1). There were no cases of seronegative spondyloarthritis or Sjögren's syndrome. CONCLUSIONS: There was an association of HIV with rheumatic conditions in 9%, including CTDs and avascular necrosis. In addition, there were no cases of the seronegative spondyloarthritis subsets. This change in spectrum from prior reports suggests the rheumatic manifestations of HIV have changed, perhaps related to HAART.
17893863 A comparison of the performance of the EQ-5D and SF-6D for individuals aged >or= 45 years. 2008 Jul We sought to compare the performance of the EQ-5D and SF-6D with regard to the criteria of practicality, convergent validity, and construct validity, the level of agreement between the two measures was also assessed. Responses from 1865 individuals aged >or= 45 years in one general practice were analysed. Of these, 93.1% completed the EQ-5D, compared with 86.4% for the SF-6D, where individuals who were older, female, of a lower occupational skill level, from an area of lower deprivation, or used prescribed medication were significantly less likely to complete the SF-6D. The performance of both measures was comparable with regard to both convergent and construct validities, as both the EQ-5D and SF-6D scores were closely related to scores on the EuroQol visual analogue scale (VAS) (p<0.001) and able to discriminate between people who did and did not take: (i) analgesics and (ii) other prescribed medication. Despite EQ-5D and SF-6D scores being highly correlated (p<0.001), individuals who were healthier (according to the VAS) had higher mean scores on the EQ-5D (p<0.001), whereas less healthy individuals had higher mean scores on the SF-6D (individuals with knee pain, osteoarthritis, back pain, rheumatoid arthritis, and hip pain had significantly lower mean scores on the EQ-5D, p<0.001).
18548252 Prevalence and clinical features of arthralgia/arthritis in healthy pregnant women. 2008 Sep The authors prospectively investigated 155 pregnant women, without a history of rheumatic disease who visited the Department of Obstetrics and Gynecology for routine antenatal care, to evaluate the prevalences and clinical features of arthralgia and arthritis in healthy pregnant women. Mean of the 155 subjects' ages was 31.8 +/- 3.8 (years, +/-SD). Arthralgia was found in 26 (16.7%) and arthritis in 15 (9.6%) pregnant women. Arthralgia or arthritis developed in the third trimester (28-40 weeks of gestation), except in one case (16 weeks of gestation). Most commonly involved joints were the proximal interphalangeal (n = 19, 12.2%). Rheumatoid factor and antinuclear antibody were negative in patients with arthritis. Ten women (6.8%) had persistent arthralgia for over 6 weeks, post-delivery. Four of them were followed up at Rheumatology Clinic and were diagnosed as having spondyloarthropathy (1), or unspecified arthralgia (3). In conclusion, arthralgia is common during pregnancy and most frequent in proximal interphalangeal joints.
17968339 A case of human T lymphotropic virus type I-associated synovial swelling. 2007 Nov BACKGROUND: Human T lymphotropic virus type 1 (HTLV-I) is associated with T-cell activation, proliferation, and leukemogenesis. HTLV-I is the causative agent of adult T cell leukemia/lymphoma and is associated with myelopathy/tropical spastic paraparesis, uveitis, polymyositis, synovitis, thyroiditis, and bronchoalveolar pneumonia. Since T-cell abnormalities are present in those infected with HTLV-I, the clinical problems might result from abnormal immune function or from direct leukemic or lymphomatous cell infiltration of tissues in the body. Distinguishing between these potential causes might be difficult in patients with joint involvement since the clinical findings can be similar. Consequently, obtaining synovial tissue for analyses is likely to be helpful in determining which process is causing the clinical symptoms. INVESTIGATIONS: Physical examination, comprehensive metabolic panel, complete blood counts, urinalysis, serological testing for rheumatoid factor, antinuclear antibodies, hepatitis, and cytomegalovirus; western blot for HTLV-I/II, lymphocyte phenotyping of peripheral blood, polymerase chain reaction, plain radiographic imaging, CT, MRI skin biopsy with immunohistochemical analysis, lymph node biopsy with immunohistochemical analysis, lymphocyte phenotyping of synovial fluid, synovial tissue biopsy with immunohistochemical analysis of synovial tissue, and synovial tissue culture. DIAGNOSIS: HTLV-I infected synovial cells in conjunction with leukemic/lymphomatous infiltration of synovial tissue. MANAGEMENT: Chemotherapy protocol using alemtuzumab.
17288836 [Inhibition of cartilage destruction in collagen-induced arthritis by altered CII 263-272 2006 Nov 21 OBJECTIVE: To study the inhibitory effect of altered collagen II (CII) 263-272 peptide (sub268-270) with three consecutive substitutions of TCR-contacting residues on joint inflammation and cartilage destruction in collagen-induced arthritis (CIA). METHODS: Thirty-two Lewis rats were injected intracutaneously with bovine collagen type II so as to establish models of arthritis and then were randomly divided into 4 equal groups to be injected intravenously with sub268-270 30 microg, 5 microg, or 1 microg and PBS twice a week for 3 weeks. The therapeutic effect of the altered peptide on arthritis was evaluated by arthritis score. After the treatment the rats were killed and their ankle joints were taken to undergo pathological examination to observe the existence of synovitis, pannus formation, cartilage damage, and bone erosion. Blood samples were collected to detect the serum cartilage oligomeric matrix protein (COMP). Cartilage proteoglycan-specific dye safranin O was used on the joint sections to observe the coloration of the dye in the cartilage. RESULTS: The arthritis score in rats treated by 30 microg altered CII peptide was (5.6 +/- 2.63), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(9.67 +/- 5.61), (10.02 +/- 5.06), and (11.8 +/- 5.34) respectively, all P < 0.01]. The synovitis score of the 30 microg group was (1.11 +/- 0.43), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.87 +/- 0.78), (2.11 +/- 0.83), and (2.25 +/- 0.73) respectively, all P < 0.01]. The pannus score of the 30 microg group was (1.11 +/- 0.43), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.83 +/- 0.79), (2.07 +/- 0.91), and (2.27 +/- 0.71) respectively, all P < 0.01]. The cartilage damage score of the 30 microg group was 0.56 +/- 0.23), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.91 +/- 0.83), (2.13 +/- 0.79), and (2.29 +/- 0.69) respectively, all P < 0.01]. The bone erosion score of the 30 microg group was (0.53 +/- 0.21), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.71 +/- 0.67), (1.88 +/- 0.93), and (2.01 +/- 0.93) respectively, all P < 0.01]. The serum COMP of the 30 microg group was (2.21 +/- 0.76), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(5.63 +/- 1.73), (6.04 +/- 1.76), and (7.00 +/- 1.46) respectively, all P < 0.01]. The content of safranin O (A value) in the joint section of the 30 microg group was (2.35 +/- 0.76), significantly higher than those of the 5 microg, 1 microg, and blank control groups [(1.57 +/- 0.63), (1.37 +/- 0.53), and (1.00 +/- 0.41) respectively, all P < 0.01]. CONCLUSION: The altered CII peptide sub268-270 effectively ameliorates CIA and inhibits the cartilage damage in CIA, and may modify the disease course of rheumatoid arthritis.
17963169 Intestinal immune activation in juvenile idiopathic arthritis and connective tissue diseas 2007 Sep OBJECTIVES: To examine the prevalence of immune activation in gastrointestinal (GI) mucosa in children with juvenile idiopathic arthritis (JIA) or connective tissue disease (CTD). STUDY DESIGN: We studied 27 children (15 girls, mean age 9.8+/-4.8 years) with JIA/CTD and GI symptoms, including nine with oligoarthritis, nine with polyarthritis, two with systemic arthritis, three with enthesitis-related arthritis, and four with various CTDs. The control group consists of 54 children (31 girls, mean age 11.3+/-6.3 years) with GI symptoms but shown to have no significant GI or rheumatoid disorder. The subjects were examined by gastroduodenoscopy (22 patients, 50 controls) and colonoscopy (23 patients, 16 controls). Intraepithelial CD3+, alpha/beta+, and gamma/delta+ lymphocytes were counted from duodenal and ileal biopsies. RESULTS: Five patients with JIA/CTD (19%) had ulcerative colitis. Lymphoid nodular hyperplasia (LNH) was more common in the patients [74% (20/27)] than in the controls [16% (8/50), p = 0.001], as well in the duodenal bulb [29% (7/24) vs. 10% (5/50)], terminal ileum [74% (14/19) vs. 38% (5/13)], and the colon [50% (11/22) vs. 14% (2/14)]. In the duodenum, CD3, alpha/beta+, and gamma/delta+ lymphocytes counts were higher in JIA/CTD (p<0.05). In the ileum, gamma/delta+ cell numbers had increased in JIA/CTD (p<0.05). Either LNH, increased gamma/delta+ count, or both were more common in JIA/CTD [89% (24/27)] than in the controls [13% (7/54), p<0.0001]. CONCLUSIONS: The majority of children suffering from JIA or CTD with GI symptoms show abnormalities consistent with activation of the intestinal immune system. The aetiology of this reaction remains unknown, but similar features are seen in delayed-type food allergy.
18425929 Exercise therapy in juvenile idiopathic arthritis. 2008 Apr 16 BACKGROUND: Exercise therapy is considered an important component of the treatment of arthritis. The efficacy of exercise therapy has been reviewed in adults with rheumatoid arthritis but not in children with juvenile idiopathic arthritis (JIA). OBJECTIVES: To assess the effects of exercise therapy on functional ability, quality of life and aerobic capacity in children with JIA. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (The Cochrane Library), MEDLINE (January 1966 to April 2007), CINAHL (January 1982 to April 2007), EMBASE (January 1966 to October 2007), PEDro (January 1966 to October 2007), SportDiscus (January 1966 to October 2007), Google Scholar (to October 2007), AMED (Allied and Alternative Medicine) (January 1985 to October 2007), Health Technologies Assessment database (January 1988 to October 2007), ISI Web Science Index to Scientific and Technical Proceedings (January 1966 to October 2007) and the Chartered Society of Physiotherapy website (http://www.cps.uk.org) were searched and references tracked. SELECTION CRITERIA: Randomised controlled trials (RCTs) of exercise treatment in JIA. DATA COLLECTION AND ANALYSIS: Potentially relevant references were evaluated and all data were extracted by two review authors working independently. MAIN RESULTS: Three out of 16 identified studies met the inclusion criteria, with a total of 212 participants. All the included studies fulfilled at least seven of 10 methodological criteria. The outcome data of the following measures were homogenous and were pooled in a meta-analysis: functional ability (n = 198; WMD -0.07, 95% CI -0.22 to 0.08), quality of life (CHQ-PhS: n = 115; WMD -3.96, 95% CI -8.91 to 1.00) and aerobic capacity (n = 124; WMD 0.04, 95% CI -0.11 to 0.19). The results suggest that the outcome measures all favoured the exercise therapy but none were statistically significant. None of the studies reported negative effects of the exercise therapy. AUTHORS' CONCLUSIONS: Overall, based on 'silver-level' evidence (www.cochranemsk.org) there was no clinically important or statistically significant evidence that exercise therapy can improve functional ability, quality of life, aerobic capacity or pain. The low number of available RCTs limits the generalisability. The included and excluded studies were all consistent about the adverse effects of exercise therapy; no short-term detrimental effects of exercise therapy were found in any study. Both included and excluded studies showed that exercise does not exacerbate arthritis. The large heterogeneity in outcome measures, as seen in this review, emphasises the need for a standardised assessment or a core set of functional and physical outcome measurements suited for health research to generate evidence about the possible benefits of exercise therapy for patients with JIA. Although the short-term effects look promising, the long-term effect of exercise therapy remains unclear.
19102051 The frequency of autoimmune thyroid disorders in juvenile idiopathic arthritis. 2008 Sep Few studies have been performed to investigate autoimmune diseases associated with organ non-specific rheumatological disorders in children, such as juvenile idiopathic arthritis (IA). The objective in this study was to determine the frequency of autoimmune diseases of the thyroid gland in children with JIA. Eighty patients with JIA and 81 healthy sex- and age-matched controls were enrolled in the study. Serum free T3, free T4, thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies, and anti-peroxidase antibodies were evaluated. The mean age was 11.5 +/- 5.5 years in the patient group and 10.5 +/- 4.9 years in the control group. Twenty-seven of the cases were classified as oligoarticular, 26 as polyarticular, 17 as enthesitis-related, 6 as systemic, and 4 as psoriatic arthritis. Autoimmune thyroid disease was found in 4 patients in the JIA group (5%). There were no significant differences between the study and control groups regarding the existence of anti-thyroid antibodies (p = 0.17). Girls were more likely to develop autoimmune thyroiditis (3 girls, 1 boy). Autoimmune thyroiditis was more frequent in patients who had a family history of thyroid disease (p = 0.02). There was no statistical correlation between rheumatoid factor (RF) and antinuclear antibody (ANA) positivity and autoimmune thyroiditis (p > 0.05). We conclude that there is no need for routine screening of serum thyroid function tests and thyroid antibody levels in patients with JIA in the absence of clinical symptoms.
18520574 Pulmonary extramedullary hematopoiesis. 2008 May Extramedullary hematopoiesis (EMH) is the formation and development of blood cells outside of the bone marrow. Of particular interest to chest physicians and radiologists is the occurrence of EMH in the lungs and pleura. There have been several reports of patients presenting with pulmonary EMH published in the literature and the majority are due to a secondary process, such as myeloproliferative disorders, hemolytic anemias, hereditary spherocytosis, and Gaucher disease. We present a case report of pulmonary EMH and a review of the literature concentrating on the etiology, clinical presentation, pathophysiology, diagnosis, and therapy for this uncommon disorder.
18328140 Increase of RP105-lacking activated B cells in the peripheral blood and salivary glands in 2008 Jan OBJECTIVE: To quantify the activated B cells in the peripheral blood and salivary glands of patients with Sjögren's syndrome (SS) by analyzing the expression of RP105 molecule on the B cells. METHODS: The expression of RP105 on the peripheral blood B cells of patients with SS (19 cases) was analyzed by flow cytometry. RP105-positive and negative B cells were sorted and cultured in vitro and the amount of immunoglobulins (IgG and IgM) produced in the supernatant was measured by enzyme-linked immunosorbent assay (ELISA). Salivary gland biopsy samples from 9 SS patients were histologically evaluated and the sequential frozen sections were separately immunostained by anti-RP105 and anti-CD20 monoclonal antibodies. RESULTS: A significantly higher proportion of peripheral blood RP105-negative B cells was found in SS patients than in healthy individuals. RP105-negative, but not positive, B cells from SS patients were capable of producing IgG and IgM spontaneously in vitro, which was enhanced by the addition of Staphylococcus aureus Cowan I strain (SAC) or IL-6. Salivary glands from 2 of 9 SS patients were found to have lymphoid follicles whose germinal centers consisted of RP105-negative B cells. Moreover, a larger proportion of B cells extensively infiltrating the area other than lymphoid follicles was also RP105-negative. CONCLUSION: RP105-negative B cells, a subset of highly activated and well differentiated B cells, which are increased in number in the peripheral blood and extensively infiltrate salivary glands, may be responsible for the production of class-switched immunoglobulin in SS. In addition, those cells might be associated with the inflammation and tissue damage of the salivary glands.
16760585 Maltoma of the thyroid and Sjögren's syndrome in a woman with Hashimoto's thyroiditis. 2006 Spring We report the case of a 70-yr-old woman with maltoma of the thyroid, Sjögren's syndrome, and a history of Hashimoto's thyroiditis. The patient underwent a total thyroidectomy for a recently growing mass of the thyroid, while being treated with L-thyroxine for Hashimoto's thyroiditis. Postoperatively, routine histologic examination was consistent with the diagnosis of chronic lymphocytic thyroiditis of autoimmune etiology. Three years later, the patient presented with high temperature, anorexia, and coughing. This time, a microscopic examination of deeper thyroid tissue sections and an immunohistochemical study revealed a low-grade, non-Hodgkin lymphoma, MALT type. Simultaneously, the diagnosis of Sjögren's syndrome was established and the patient is currently under investigation for generalized lymphoma. This case clearly demonstrates the difficulty in differentially diagnosing Hashimoto's thyroiditis from low-grade MALT lymphoma by the use of routine histologic examination.
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.
18839063 A case of glomerulopathy showing podocytic infolding in association with Sjögren's syndro 2008 Dec A 49-year-old man was admitted to our hospital with mild proteinuria. Prior to admission, he had been diagnosed as having Sjögren's syndrome in association with primary biliary cirrhosis. Examination of a renal biopsy under light microscopy revealed diffuse and global mesangial cell proliferation and a spike and/or bubbling formation of the glomerular basement membrane (GBM), resembling membranoproliferative glomerulonephritis. In contrast, immunofluorescent studies showed marked immunoglobulin and complement depositions in the mesangial areas; however, only faint granular IgG and IgA deposition was observed along the GBM. Interestingly, electron microscopy revealed that a microtubular structure, derived from podocytes, was present in the GBM. We present a case of glomerulopathy showing podocytic infolding in association with Sjögren's syndrome and primary biliary cirrhosis.
18208477 Oral diseases associated with hepatitis C virus infection. Part 1. sialadenitis and saliva 2008 Mar Morbidity associated with hepatitis C virus (HCV) infection is due not only to the sequelae of chronic liver disease, but also to a variety of extraheaptic manifestations (EHM). Some of the most frequently reported EHM of HCV infection involves the oral region predominantly or exclusively and they are the topics of this 2-part review. The current part 1 discusses the evidences on the association of salivary glands disorders with HCV. HCV- infected patients may frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, the pathogenetic role of HCV in Sjogren Syndrome (SS) development and the characteristics distinguishing classic SS from HCV-related sialadenitis are still an issue. It is unclear if the virus may cause a disease mimicking primary SS or if HCV is directly responsible for the development of SS in a specific subset of patients. Notably, some patients may present a triple association between HCV, SS-like sialadenitis and salivary gland lymphoma and the virus may be involved in the lymphomagenesis. The risk of having a salivary gland lymphoma is particularly high in patients with mixed cryoglobulinemia. Little attention has been paid to the effects of anti-HCV treatment on sialadenitis or lymphoma development.