Rheumatoid Arthritis Research Today is a free monthly online journal that collates and summarizes the latest research about Rheumatoid Arthritis, including details on treatment, symptoms, causes, medication.

Lymphocytic infiltration leads to degradation of lacrimal gland extracellular matrix structures in NOD mice exhibiting a Sjögren's syndrome-like exocrinopathy.

Schenke-Layland K, Xie J, Magnusson M, Angelis E, Li X, Wu K, Reinhardt DP, Maclellan WR, Hamm-Alvarez SF

Department of Medicine/Cardiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1760, USA. kschenkelayland@mednet.ucla.edu

We previously reported that lacrimal glands (LGs) of male non-obese diabetic (NOD) mice, an established mouse model of autoimmune inflammatory LG disease that displays many features of human LGs in patients afflicted with Sjögren's syndrome (SjS), exhibit significant degradation of extracellular matrix (ECM) structures as well as increased expression of matrix metalloproteinases (MMPs). The purpose of the current study was to expand the spectrum of proteases identified, to clarify their probable origin as well as to identify the contribution of these changes to disease pathogenesis. We explored in depth the changes in ECM structures and ECM protease expression at the onset of disease (6 weeks) versus late stage disease (18 weeks) in male NOD mouse LGs, relative to LGs of age-matched male NODscid, a severely immunocompromised congenic strain, and healthy BALB/c mice. LG tissues were examined using routine histological, immunohistochemical, Western Blot and gene expression analyses novel multiphoton imaging technologies. We further characterized the profile of infiltrating immune cells under each condition using flow cytometry. Our results show that the initial infiltrating cells at 6 weeks of age are responsible for increased MMP and cathepsin H expression and therefore initiate the LG ECM degradation in NOD mice. More importantly, NODscid mice exhibited normal LG ECM structures, indicating the lymphocytes seen in the LGs of NOD mice are responsible for the degradation of the LG ECM. The disease-related remodeling of LG ECM structures may play a crucial role in altering the acinar signaling environment, disrupting the signaling scaffolds within the cells, which are required to mobilize the exocytotic trafficking machinery, ultimately leading to a loss of LG function in patients afflicted with SjS.

Published 15 February 2010 in Exp Eye Res, 90(2): 223-37.
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Articles on Rheumatoid Arthritis published 4 February 2010:

Migration of the humeral component of the Souter-Strathclyde elbow prosthesis: a long-term RSA study.   J Bone Joint Surg Br, 92(2): 235-41.

Mechanical loosening which begins with early-onset migration of the prosthesis is the major reason for failure of the Souter-Strathclyde elbow replacement. In a prospective study of 18 Souter-Strathclyde replacements we evaluated the patterns of migration using roentgen stereophotogrammetric analysis. We had previously reported the short-term results after a follow-up of two years which we have now extended to a mean follow-up of 8.2 years (1 to 11.3). Migration was assessed along the ... [Abstract] [Full-text]

Distribution of circulating cells in systemic juvenile idiopathic arthritis across disease activity states.   Clin Immunol, 134(2): 206-16.

Juvenile idiopathic arthritis (JIA) encompasses a group of chronic childhood arthritides of unknown etiology. One subtype, systemic JIA (SJIA), is characterized by a combination of arthritis and systemic inflammation. Its systemic nature suggests that clues to SJIA pathogenesis may be found in examination of peripheral blood cells. To determine the immunophenotypic profiles of circulating mononuclear cells in SJIA patients with different degrees of disease activity, we studied PBMC from 31 SJIA ... [Abstract] [Full-text]

Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFalpha blockers: safety and immunogenicity.   Clin Immunol, 134(2): 113-20.

Twenty-eight patients with low-moderate, stable rheumatoid arthritis (RA), under treatment with tumor necrosis factor (TNF) alpha blockers, were immunized at least once with non-adjuvanted trivalent influenza vaccine during three consecutive influenza seasons. Antibodies toward A influenza antigens significantly increased and reached protective levels, still detectable 6 months after vaccination, both in RA patients and healthy controls. Response to B antigen instead was only observed from the ... [Abstract] [Full-text]

Articles on Rheumatoid Arthritis published 3 February 2010:

Activating NK-cell receptors co-stimulate CD4(+)CD28(-) T cells in patients with rheumatoid arthritis.   Eur J Immunol, 40(2): 378-87.

Effector T-cell responses can be modulated by competing positive or negative signals transduced by NK-cell receptors (NKR). In the CD4(+) T-cell population, the expression of NKR is primarily found in the CD4(+)CD28(-) T-cell subset, also known as CD28(null) T cells. These T cells are frequently found in rheumatoid arthritis (RA) and other inflammatory disorders, suggesting that signaling through NKR may play a role in the autoimmune reaction. Here we aimed to dissect the phenotype and function ... [Abstract] [Full-text]

Articles on Rheumatoid Arthritis published 1 February 2010:

GDF-5 is suppressed by IL-1beta and enhances TGF-beta3-mediated chondrogenic differentiation in human rheumatoid fibroblast-like synoviocytes.   Exp Mol Pathol, 88(1): 163-70.

OBJECTIVE: To investigate the expression of growth differentiation factor-5 (GDF-5) in chondrocytes (HC) and fibroblast-like synoviocytes (FLS) from humans with rheumatoid arthritis (RA) when stimulated with proinflammatory cytokines and to explore whether GDF-5 plays a role in regulating the differentiation of FLS-RA into chondrocytes. METHODS: Expression of GDF-5 in synovium and cartilage in RA and osteoarthritis (OA) was assessed by immunohistochemistry. GDF-5 production in FLS-RA and HC-RA ... [Abstract] [Full-text]

Articles on Rheumatoid Arthritis published 29 January 2010:

Platelets amplify inflammation in arthritis via collagen-dependent microparticle production.   Science, 327(5965): 580-3.

In addition to their pivotal role in thrombosis and wound repair, platelets participate in inflammatory responses. We investigated the role of platelets in the autoimmune disease rheumatoid arthritis. We identified platelet microparticles--submicrometer vesicles elaborated by activated platelets--in joint fluid from patients with rheumatoid arthritis and other forms of inflammatory arthritis, but not in joint fluid from patients with osteoarthritis. Platelet microparticles were proinflammatory, ... [Abstract] [Full-text]

Articles on Rheumatoid Arthritis published 28 January 2010:

EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis.   Ann Rheum Dis, 69(2): 325-31.

OBJECTIVES: To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related ... [Abstract] [Full-text]

Postpartum onset of rheumatoid arthritis and other chronic arthritides: results from a patient register linked to a medical birth registry.   Ann Rheum Dis, 69(2): 332-6.

BACKGROUND: It is known that onset of rheumatoid arthritis (RA) is increased post partum. OBJECTIVE: To compare incidence rates between RA and other chronic arthritides (OCA) 0-24 months after delivery, and to compare the incidence rates within each group 0-24 versus 25-48 months post partum. METHODS: Premenopausal women from a Norwegian patient register were linked with the Medical Birth Registry of Norway to study the interval between delivery and time of diagnosis. Cox regression analysis ... [Abstract] [Full-text]

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