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Autoimmune Models (autoimmune + models)
Selected AbstractsGenetic analysis of collagen-induced arthritis in rats: a polygenic model for rheumatoid arthritis predicts a common framework of cross-species inflammatory/autoimmune disease lociIMMUNOLOGICAL REVIEWS, Issue 1 2001Marie M. Griffiths Summary: Collagen-induced arthritis (CIA) is a useful model for dissecting the genetic patterns underlying susceptibility to rheumatoid arthritis (RA) and related chronic/inflammatory autoimmune diseases. CIA exhibits three phenotypes characteristic of autoimmune disease pathogenesis: abnormal levels of immune reactivity to self antigens; chronic inflammation of target organs expressing that specific autoantigen; activation and direct participation of invading mononuclear cells and resident tissue fibroblasts in organ damage. Over 25 different quantitative trait loci (QTL) regulating arthritis severity and autoantibody in rats with CIA are mapped. QTL-congenic strains show that certain CIA,QTLs can modulate arthritis independently. These monogenic models are proving to be highly informative for fine mapping and function studies, revealing gender effects and evidence of gene clusters. Recent genome scans of RA populations identified RA-susceptibility loci in chromosome regions homologous to rat chromosomal segments housing CIA,QTLs. Also, CIA,QTLs frequently co-localize with susceptibility QTLs mapped in other rat arthritis models induced with non-immunogenic adjuvant oils and/or in rat autoimmune models of multiple sclerosis and diabetes. Common autoimmunity genes and inflammation genes important to several human diseases are likely being detected in the various rat disease models. Continued dissection of the genetic underpinnings of rat arthritis models should provide candidate genes for investigation in human patients and lead to a clearer understanding of the complex genetics of RA. [source] Arthritis induced in rats with non-immunogenic adjuvants as models for rheumatoid arthritisIMMUNOLOGICAL REVIEWS, Issue 1 2001Rikard Holmdahl Summary: Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of ,,TCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans. [source] The effect of immunomodulators on prevention of autoimmune diabetes is stage dependent: FTY720 prevents diabetes at three different stages in the diabetes-resistant biobreeding ratPEDIATRIC DIABETES, Issue 1 2004Jadranka Popovic Abstract:, Background:, Autoimmune diabetes of the diabetes-resistant biobreeding (DRBB) rat shares similarities with diabetes in humans and has stages of diabetes that can be controlled and compared. FTY720 is an immunomodulator that has been efficacious in transplant and autoimmune models without inducing an immunosuppressed state. We determined the stages of diabetes that are affected by FTY720 in the DRBB rat. Methods:, Autoimmune diabetes was induced with RT6.1 T-cell-depleting antibody and polyIC starting at 4 weeks of age. FTY720 (1 mg/kg/d) was started at day 0, 5, 7, and 14 following the start of depletion. The rats that did not develop diabetes were maintained for 60 d following the last dose of FTY720 before undergoing a second course of depletion. Results:, FTY720 starting at day 0, 5, 7, and 14 of depletion prevented diabetes in 100, 100, 50, and 20% of the DRBB rats compared to 0% of the control rats. The surviving rats in the 5-, 7-, and 14-d groups developed diabetes after FTY720 treatment was stopped. Histological examination indicated insulitis in the control rats between day 7 and 11 of depletion and end-stage insulitis by day 18 of depletion compared to negligible insulitis in rats without diabetes. Redepletion in the surviving day 0 rats resulted in development of diabetes in 25% of these rats compared to none of the age-matched controls. Summary:, FTY720 can prevent autoimmune diabetes, if administered before and/or during stimulation and expansion of the autoreactive T cells or in the early stages of insulitis. The effectiveness diminishes with each successive stage of diabetes. [source] Therapeutic effects of interleukin-6 blockade in a murine model of polymyositis that does not require interleukin-17AARTHRITIS & RHEUMATISM, Issue 8 2009Naoko Okiyama Objective To explore new molecular targets in the treatment of polymyositis (PM) by examining a recently established murine model of PM, C protein,induced myositis (CIM), for involvement of an interleukin-6 (IL-6)/IL-17A pathway. Methods CIM was induced by immunizing wild-type mice as well as IL-6,null and IL-17A,null C57BL/6 mice with recombinant mouse skeletal C protein fragments. Some mice were treated with anti,IL-6 receptor (anti,IL-6R) monoclonal antibodies or control antibodies. Muscle tissue samples were examined histologically and immunohistochemically. Results The syngeneic C protein fragments successfully induced inflammation in the skeletal muscles of wild-type mice. IL-6 was expressed by mononuclear cells, especially in macrophages, infiltrating in the muscles. IL-6,null mice developed myositis with significantly lower incidence and milder severity than wild-type mice. In contrast, IL-17A,null mice were as susceptible to CIM as wild-type mice. Intraperitoneal administration of anti,IL-6R monoclonal antibodies, but not of control monoclonal antibodies, ameliorated CIM both preventively and therapeutically. Conclusion Our findings indicate that IL-6 is critically involved in the development of CIM. Although many other autoimmune models require IL-6 for differentiation of pathogenic T cells producing IL-17A, IL-17A was dispensable in CIM. Nevertheless, treatment with anti,IL-6R antibodies was effective. IL-6 blockade is potentially a new approach to the treatment of autoimmune myositis, via processes distinct from interference in the IL-6/IL-17A pathway. [source] Dyskinesias and associated psychiatric disorders following streptococcal infectionsCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 6 2004Richard Reading Dyskinesias and associated psychiatric disorders following streptococcal infections . DaleRC, HeymanI, SurteesRAH, ChurchAJ, GiovannoniG, GoodmanR & NevilleBGR . ( 2004 ) Archives of Disease in Childhood , 89 , 604 , 610 . Background The classical extrapyramidal movement disorder following , haemolytic streptococcus (BHS) infection is Sydenham's chorea (SC). Recently, other post-streptococcal movement disorders have been described, including motor tics and dystonia. Associated emotional and behavioural alteration is characteristic. Aims To describe experience of post-streptococcal dyskinesias and associated comorbid psychiatric features presenting to a tertiary referral centre 1999,2002. Methods In all patients, dyskinetic movement disorders followed BHS pharyngeal infection. BHS infection was defined by pharyngeal culture of the organism, or paired streptococcal serology. Movement disorders were classified according to international criteria, and validated by experienced child neurologists. Psychiatric complications were defined using ICD-10 criteria using a validated psychiatric interview. Results In the 40 patients, the following dyskinetic movement disorders were present: chorea (n = 20), motor tics (n = 16), dystonia (n = 5), tremor (n = 3), stereotypies (n = 2), opsoclonus (n = 2) and myoclonus (n = 1). Sixty-five per cent of, the, chorea, patients, were, female,, whereas, 69% of the tic patients were male. ICD-10 psychiatric diagnoses were made in 62.5%. Using the same psychiatric instrument, only 8.9% of UK children would be expected to have an ICD-10 psychiatric diagnosis. Emotional disorders occurred in 47.5%, including obsessive-compulsive disorder (27.5%), generalized anxiety (25%) and depressive episode (17.5%). Additional psychiatric morbidity included conduct disorders (27.5%) and hyperkinetic disorders (15%). Psychiatric, movement and post-streptococcal autoimmune disorders were commonly observed in family members. At a mean follow-up of 2.7 years, 72.5% had continuing movement and psychiatric disorders. Conclusion Post-streptococcal dyskinesias occur with significant and disabling psychiatric comorbidity and are potential autoimmune models of common ,idiopathic' movement and psychiatric disorders in children. Multiple factors may be involved in disease expression including genetic predisposition, developmental status and the patient's sex. [source] | ||||||||||