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ID PMID Title PublicationDate abstract
18056756 Modulation of established murine collagen-induced arthritis by a single inoculation of sho 2008 Sep BACKGROUND: The use of regulatory or immature dendritic cells (DCs) as tools for modulating experimental rheumatoid arthritis is very recent. Tumour necrosis factor (TNF)-stimulated DCs have been shown to restore tolerance in experimental autoimmune encephalomyelitis and collagen-induced arthritis (CIA). OBJECTIVE: We investigated the capacity of short-term lipopolysaccharide (LPS)-stimulated DCs pulsed with type II collagen (CII) to induce tolerance against established CIA. METHODS: Bone marrow-derived DCs were generated in the presence of granulocyte monocyte colony-stimulating factor (GM-CSF). After CIA induction, mice were injected at day 35 with a single dose of 4- or 24-h LPS-stimulated DCs that had been loaded with CII (4hLPS/CII/DCs or 24hLPS/CII/DCs). Arthritis progression was monitored by clinical and histological evaluations. RESULTS: Flow cytometry of 4hLPS/CII/DCs showed intermediate CD40 and CD86 expression, lower than that of 24hLPS/CII/DCs (fully mature) and higher than that of CII/DCs (immature). A functional assay showed that 4hLPS/CII/DCs display increased endocytosis ability with respect to 24hLPS/CII/DCs, indicating a semimature state. The single inoculation of 4hLPS/CII/DCs in mice with established CIA reduced disease severity significantly over time. Histological evaluation of mice treated with 4hLPS/CII/DCs revealed diminished inflammatory synovitis, cartilage damage and fibrosis. Co-cultures of DCs with splenocytes from CIA mice showed that collagen-specific interferon (IFN)gamma production was dramatically inhibited by 4hLPS/CII/DCs. 4hLPS/CII/DCs were high IL10 producers, which could explain the inhibition of arthritis progression in mice receiving this treatment because neither antibodies nor regulatory CD4+CD25+Foxp3+ T lymphocytes were demonstrated to be involved. CONCLUSION: Short-term LPS-modulated DCs inoculation interferes with CIA progression when loaded with CII.
17164994 Differences in osteoclast formation between proximal and distal tibial osteoporosis in rat 2006 Patients with rheumatoid arthritis commonly suffer both systemic and periarticular osteoporosis. Bisphosphonates (BPs) are inhibitors of bone resorption, and several derivatives have been developed for treatment of enhanced bone resorption. We aimed to characterize osteoclast formation in two different sites, the proximal tibial and distal tibial areas, in rats with adjuvant arthritis, and to investigate the impact of amino or non-amino types of bisphosphonate. Adjuvant arthritis was initiated in rats while administering daily injections of either etidronate, a non-amino BP, or alendronate, an amino BP, for 3 weeks. On the day following the last injection, bone mineral density (BMD) was measured in the proximal tibia to assess systemic osteoporosis and in the distal tibia for periarticular osteoporosis using dual-energy X-ray absorptiometry. Subsequently, bone marrow cells from either end of the tibia were collected and incubated for 7 days before staining and counting tartrate-resistant acid phosphatase positive cells. In the rats with adjuvant arthritis, BMD of either end of the tibia was lower than in normal rats. Although etidronate prevented bone mineral loss at both ends, distal loss was significantly less than proximal. In contrast, alendronate significantly inhibited mineral loss primarily in the proximal area. Large osteoclasts, defined as having five or more nuclei, formed preferentially in the proximal tibia, while small osteoclasts with fewer than four nuclei were found mainly distally. The suppressive effect of alendronate was greater on the large osteoclasts, while etidronate had a greater effect on the small osteoclasts. These results show that the size and multinuclearity of osteoclasts and the number of osteoclasts formed are different in the distal and proximal areas of the tibia, and that alendronate and etidronate may suppress different types of osteoclasts as discriminated by the number of nuclei.
18584268 A prospective study of the incidence and characteristics of septic arthritis in a teaching 2008 Nov To find the incidence, characteristics, method of treatment, and outcome of synovial fluid culture-positive septic arthritis, all newly admitted cases of synovial fluid culture-positive septic arthritis to King Khalid University Hospital, Riyadh, Saudi Arabia were studied prospectively during August 2005 to July 2006 and only those with positive synovial fluid culture septic arthritis were included in the analysis. Demographic, clinical, hematological, biochemical, microbiological, radiological, and histopathological data along with the interventional and surgical procedures and the functional outcome related to the joint involved were recorded. Of the 42 patients admitted, only 12 fulfilled the study criteria of having positive synovial fluid culture. Annual incidence was estimated to be 2.13 per 100,000 inhabitants. The mean disease duration before diagnosis and treatment was 10.42 +/- 2.9 days. The affected joints were six knees, three hips, two shoulders, and one with hip and knee involvement. Two patients had rheumatoid arthritis, two had osteoarthritis, and one had sickle cell disease. The most common infecting organism was Staphylococcus aureus, which caused eight of the infections (66.7%), one Salmonella, one Staphylococcus epidermidis, one Enterobacter cloacae, and one Mycobacterium tuberculosis. The septic arthritis in 4 (33.3%) cases followed previous orthopedic intervention. Blood cultures were positive in three patients, all with S. aureus. White blood cell count was elevated in 3 (25%) patients. All patients received intravenous antibiotic for the initial 2 weeks, the most commonly used antibiotic was flucloxacillin. There were no deaths due to septic arthritis. The functional outcome was excellent to good. Septic arthritis is less prevalent in our community, and the most frequent organism is Staphylococcus. However, special risk factors favor other organisms such as Salmonella and Enterobacter. Previous orthopedic intervention is an important risk factor. Mortality due to septic arthritis is lower than reported elsewhere.
18383372 In vivo delivery of lentiviral vectors expressing vasoactive intestinal peptide complement 2008 Apr OBJECTIVE: Vasoactive intestinal peptide (VIP) has been shown to exert potent immunomodulatory activity, and the use of lentiviral vectors has been found to be an effective means of gene delivery. The present study was therefore undertaken to investigate the feasibility and efficiency of gene therapy using lentiviral vectors expressing VIP (LentiVIP) for the treatment of rheumatoid arthritis (RA). METHODS: We evaluated the therapeutic potential of the gene therapy strategy in the collagen-induced arthritis (CIA) mouse model, administering the vectors at different phases of the disease. The inflammatory response was determined by measuring the levels of various inflammatory cytokines and chemokines in the joints and serum. The Th1-mediated response was evaluated by determining the proliferative response and cytokine profile of T cells stimulated with autoantigen. RESULTS: A single intraperitoneal injection of LentiVIP was highly effective in treating CIA. Mice with established, severe arthritis showed complete regression of the disease. The therapeutic effect of LentiVIP was associated with widespread biodistribution of the vector and increased VIP levels, especially in joints and lymphoid organs, and was mediated through a striking reduction of the 2 deleterious components of the disease, i.e., the autoimmune response (self-reactive Th1 cell activity and autoantibody production) and the inflammatory response. LentiVIP treatment also induced the generation and/or activation of CD4+,CD25+,FoxP3+ Treg cells in arthritic mice. CONCLUSION: Our findings show that in vivo administration of lentiviral vector expressing VIP produces one of the most potent therapeutic effects described so far in any animal model of RA. We propose that VIP gene transfer should be further investigated as a potential novel, effective treatment of RA and other chronic autoimmune disorders.
17907171 Role of raloxifene as a potent inhibitor of experimental postmenopausal polyarthritis and 2007 Oct OBJECTIVE: In postmenopausal rheumatoid arthritis (RA), both estrogen deficiency and the inflammatory disease contribute to the development of generalized osteoporosis. Hormone replacement therapy (HRT) with estradiol preserves bone mineral density (BMD) and ameliorates arthritis, but long-term therapy is no longer an option due to significant side effects. We therefore used a mouse model of human RA to test the hypothesis that a selective estrogen receptor modulator (SERM), the raloxifene analog LY117018, could be beneficial in the treatment of both arthritis and osteoporosis. METHODS: Female DBA/1 mice were ovariectomized and arthritis was induced with collagen immunization. Mice received an injection of raloxifene, estradiol, or vehicle control, administered prophylactically or therapeutically, and thereafter the clinical arthritis score was evaluated continuously. At termination, BMD was analyzed with peripheral quantitative computed tomography. Paws were collected for histology, and sera were analyzed for cytokines and markers of bone and cartilage turnover. Levels of cytokine messenger RNA (mRNA) were investigated with real-time polymerase chain reaction. RESULTS: Treatment with raloxifene dramatically decreased the frequency and severity of arthritis. Effective preservation of bone and cartilage was seen in raloxifene-exposed mice, as demonstrated by increased BMD and decreased serum levels of cartilage oligomeric matrix protein in the raloxifene-treated mice compared with controls. Decreased levels of mRNA for both tumor necrosis factor alpha and RANKL in spleen cells from raloxifene-treated arthritic mice indicated an immunosuppressive action of this SERM. CONCLUSION: In a well-established model of postmenopausal RA, the raloxifene analog LY117018 potently inhibits the progression of arthritis and the associated development of osteoporosis, both in a prophylactic and in a therapeutic regimen. Since long-term HRT has been associated with significant side effects, raloxifene may be a useful adjuvant treatment for postmenopausal RA.
17353105 Suppressive effects of Chelidonium majus methanol extract in knee joint, regional lymph no 2007 May 30 Chelidonium majus L. has multiple applications in Korean traditional medicine because of its anti-tumoral, cytotoxic, anti-inflammatory and anti-microbial activities and has long been known to have anti-inflammatory effects. However, no study on the anti-arthritic activity of Chelidonium majus has been reported in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Cytokine production and gene expression were assessed during CIA (collagen-induced arthritis) model mice in knee joint, lymph node (LN), and spleen, using ELISA and competitive RT-PCR. DBA/1J mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with CME orally at 400, 40mg/kg once a day for 4 weeks. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Administration of CME significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IL-6 in spleen and lymph node. The erosion of cartilage was dramatically reduced in mouse knees after treatment with CME. In conclusion, our results demonstrates that CME significantly suppressed the progression of CIA and that this action was characterized by the decreased production of TNF-alpha, IL-6, IFN-gamma, B cells, gammadelta T cells (in spleen) and increased proportion of CD4+CD25+ regulatory T cells in vivo. In the serum of CME-treated mice, the levels of IgG and IgM RA factor were decreased.
17490473 Arthritis suppression by NADPH activation operates through an interferon-beta pathway. 2007 May 9 BACKGROUND: A polymorphism in the activating component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, neutrophil cytosolic factor 1 (NCF1), has previously been identified as a regulator of arthritis severity in mice and rats. This discovery resulted in a search for NADPH oxidase-activating substances as a potential new approach to treat autoimmune disorders such as rheumatoid arthritis (RA). We have recently shown that compounds inducing NCF1-dependent oxidative burst, e.g. phytol, have a strong ameliorating effect on arthritis in rats. However, the underlying molecular mechanism is still not clearly understood. The aim of this study was to use gene-expression profiling to understand the protective effect against arthritis of activation of NADPH oxidase in the immune system. RESULTS: Subcutaneous administration of phytol leads to an accumulation of the compound in the inguinal lymph nodes, with peak levels being reached approximately 10 days after administration. Hence, global gene-expression profiling on inguinal lymph nodes was performed 10 days after the induction of pristane-induced arthritis (PIA) and phytol administration. The differentially expressed genes could be divided into two pathways, consisting of genes regulated by different interferons. IFN-gamma regulated the pathway associated with arthritis development, whereas IFN-beta regulated the pathway associated with disease protection through phytol. Importantly, these two molecular pathways were also confirmed to differentiate between the arthritis-susceptible dark agouti (DA) rat, (with an Ncf-1DA allele that allows only low oxidative burst), and the arthritis-protected DA.Ncf-1E3 rat (with an Ncf1E3 allele that allows a stronger oxidative burst). CONCLUSION: Naturally occurring genetic polymorphisms in the Ncf-1 gene modulate the activity of the NADPH oxidase complex, which strongly regulates the severity of arthritis. We now show that the Ncf-1 allele that enhances oxidative burst and protects against arthritis is operating through an IFN-beta-associated pathway, whereas the arthritis-driving allele operates through an IFN-gamma-associated pathway. Treatment of arthritis-susceptible rats with an NADPH oxidase-activating substance, phytol, protects against arthritis. Interestingly, the treatment led to a restoration of the oxidative-burst effect and induction of a strikingly similar IFN-beta-dependent pathway, as seen with the disease-protective Ncf1 polymorphism.
16513099 Curative effect of Semecarpus anacardium Linn. nut milk extract against adjuvant arthritis 2006 Apr 15 Localised bone loss in the form of bone erosions and peri-articular osteopenia constitutes an important criteria for the diagnosis of rheumatoid arthritis. In the present study, the effect of Semecarpus anacardium Linn. nut milk extract (SA) on the metabolism of bone turn over has been studied by analyzing various markers of bone turnover and by histological and radiological analysis of the joints in adjuvant arthritis in rats. Arthritis was induced in rats by injecting Freund's complete adjuvant containing 10mg of heat killed mycobacterium tuberculosis in 1 ml paraffin oil (0.1 ml) into the left hind paw of the rat intradermally. After 14 days of induction, SA (150 mg/kg body weight/day) was administered orally by gastric intubations for 14 days. SA significantly reverted the alterations in the bone turnover observed in arthritic animals by modulating the levels of calcium, phosphorus and the activities of the enzymes names tartrate resistant acid phosphatase, acid phosphatase and alkaline phosphatase. The drug increased the bone weights that were found to be decreased during arthritis. Protective effect of SA was also observed by the decrease in the levels and expression of tumour necrosis factor alpha (TNF-alpha) as well as the histopathological and radiological observations. From all these observations it can be concluded that SA possesses strong anti-arthritic property by regulating bone turnover.
17600295 Challenges in pulmonary fibrosis. 2: Bronchiolocentric fibrosis. 2007 Jul Bronchiolocentric fibrosis is essentially represented by the pathological pattern of constrictive fibrotic bronchiolitis obliterans. The corresponding clinical condition (obliterative bronchiolitis) is characterised by dyspnoea, airflow obstruction at lung function testing and air trapping with characteristic mosaic features on expiratory high resolution CT scans. Bronchiolitis obliterans may result from many causes including acute diffuse bronchiolar damage after inhalation of toxic gases or fumes, alloimmune chronic processes after lung or haematopoietic stem cell transplantation, or connective tissue disease (especially rheumatoid arthritis). Airway-centred interstitial fibrosis and bronchiolar metaplasia are other features of bronchiolocentric fibrosis.
18680688 [What is special about adalimumab?]. 2008 Feb Adalimumab is the first fully human anti-tumor necrosis factor (TNF-alpha) monoclonal antibody and it binds to both soluble and cell-bound TNF-alpha, modulating biological responses linked to this cytokine. Different trials have probed the efficacy of adalimumab even after one week, and accumulated experience in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease shows adalimumab as a safe drug sharing a similar adverse effects profile with the other anti-TNF-alpha molecules. Specific features of adalimumab are revised.
17998070 Hypoxic regulation of NF-kappaB signaling. 2007 Hypoxia and inflammation are coincidental events in an array of diseased tissues, including chronically inflamed sites (e.g., inflammatory bowel disease, rheumatoid arthritis), growing tumors, myocardial infarcts, atherosclerotic plaques, healing wounds, and sites of bacterial infection (Murdoch et al., 2005). An understanding of how hypoxia modulates the inflammatory response is critical in developing our fundamental understanding of inflammatory disease and identifying new windows of therapeutic opportunity. Nuclear factor-kappaB (NF-kappaB) is a master transcriptional regulator of inflammatory and antiapoptotic gene expression, the activation of which has significant implications in disease development. Recent work has uncovered mechanisms by which hypoxia modulates the activation of NF-kappaB in cells through decreased oxygen-dependent suppression of the key regulators of this pathway. This work has implicated a novel role for proline and asparagine hydroxylases in the modulation of NF-kappaB activity. Here, we describe methodologies used to demonstrate and interrogate hypoxic induction of the NF-kappaB pathway.
16584963 Atraumatic joint and limb pain in the elderly. 2006 May Patients who visit the emergency department often have complaints of joint and limb pain. The differential diagnosis, clinical presentation, and treatment choices can be vastly different in the young- or middle-aged population compared with the elderly population, and the concerns of each group must be addressed. The emergency physician is in a unique position in that they are frequently the first to see these individuals and have the opportunity to intervene before permanent disability ensues. Some of the more common etiologies of atraumatic joint and limb pain, including crystal deposition diseases such as gout and pseudogout, osteoarthritis, septic arthritis, and inflammatory arthritides such as rheumatoid arthritis will be addressed in this article. In addition,several arthritides specific to the elderly population such as poly-myalgia rheumatica and associated giant cell arteritis will be covered. Finally a discussion of cervical and lumbar disc disease, as well as gait disorders, and their impact on the elderly, will be presented.
19707319 Drug focus: adalimumab in the treatment of moderate to severe psoriasis. 2007 Jun Adalimumab is a fully human IgG1 monoclonal antibody that specifically binds to tumor necrosis factor (TNF)-alpha, and is administered by subcutaneous injection. The mechanism of action is based on both the neutralization of TNF-alpha bioactivity and the induction of apoptosis of TNF-expressing mononuclear cells. The drug is approved for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis (PsA), and recently also for the treatment of Crohn's disease. The effectiveness of adalimumab in psoriasis was previously suggested by the subset analysis of patients enrolled in PsA trials who were affected by concomitant psoriasis, and recently confirmed by a phase II trial and the preliminary results from phase III trials in moderate to severe psoriasis. These results demonstrate that adalimumab is effective in improving psoriasis and quality of life, with sustained effects over >/= 1-year treatment period. The safety data from psoriasis studies were similar to those of previous studies in other diseases. The risk of adverse events did not appear to increase with continuous long-term exposure to adalimumab.
17456023 The contribution of adipose tissue and adipokines to inflammation in joint diseases. 2007 Adipokines are proteins produced by white adipose tissue, which is an active secretory organ. Regulation of immune and inflammatory responses is among the multiple physiological processes involving adipokines. Leptin, adiponectin and resistin are the most extensively studied adipokines. Leptin may promote inflammation by inducing Th1 phenotype development, whereas adiponectin may combat inflammation by reducing the production of pro-inflammatory cytokines. Resistin belongs to a family of proteins found in foci of inflammation, where they contribute to the inflammatory response. All three adipokines have been detected in synovial fluid from joints affected with the inflammatory disease rheumatoid arthritis (RA) or the degenerative disease osteoarthritis (OA). Recent evidence points to involvement of leptin in RA and OA and indicates that adiponectin and/or resistin mediate inflammation in arthritis. Thus, fat tissue is an active organ whose products contribute to inflammatory and degenerative processes underlying common joint diseases.
17223974 Rheumatoid factor induction in murine models of liver injury. 2007 Feb Alcoholic liver disease and hepatitis C are associated with the production of autoantibodies such as rheumatoid factors (RF), which bind to IgG and can aid in host defence, but are also associated with pathological conditions such as rheumatoid arthritis. Because little is known about the role of RF in liver disease, we characterized the RF production that either occurred spontaneously in response to alcohol consumption or was induced by injection of an Escherichia coli glycolipoprotein in C57Bl/6 mice. Whereas severe liver damage was induced by carbon tetrachloride (CCl(4)), minimal damage was caused by chronic alcohol consumption. Liver damage was monitored by measurements of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Circulating RF was induced in response to chronic alcohol consumption; the latter probably involved Toll-like receptor ligation. In contrast, CCl(4)-induced damage was not associated with RF induction. However, concurrent treatment with an E. coli glycolipoprotein macromolecule that induced RF, protected against CCL(4)-induced liver damage as measured by a highly significant decrease (P = 0.008) at 4 weeks in AST and ALT. RF induced by E. coli glycolipoprotein correlated with 'protection' from liver damage, indicating that the RF autoimmune response does not necessarily exacerbate liver disease.
18820931 High prevalence of rheumatoid factor associated with clinical manifestations of rheumatic 2009 Feb The aim of the present study was to perform a screening for rheumatoid factor (RF) and anti-nuclear antibody in Kaingang, Guarani and Mestizos individuals from Mangueirinha Reservation, State of Paraná, Brazil, and associate it with demographic and clinical data. Serum samples from 321 aborigines (125 male and 196 female; 4-86 years old) and 180 non-Indians healthy individuals were analysed (62 male and 118 female; 2-81 years old). Antinuclear antibody (ANA) was tested by indirect immunofluorescence, and RF by agglutination in latex and turbidimetry. RF was higher in Kaingang when compared to Guarani (P = 0.009), Mestizos (P = 0.061) and non-Indians (P = 0.010). A significant increase of RF was observed in Kaingang women versus Kaingang men (P = 0.002) and, among the women, in Kaingang when compared to Mestizos and Guarani (P
18974624 [Immunotherapy using IL-6 receptor as the target]. 2008 Oct Monoclonal antibody-based therapy targeting interleukine-6 (IL-6) has been established as a treatment for autoimmune diseases, chronic inflammatory diseases, and lymphoproliferative disease. IL-6 is a multifunctional cytokine which plays pathological roles in Castleman's disease, rheumatoid arthritis, juvenile idiopathic arthritis, and Crohn's disease. Many groups have been exploring the therapeutic approach to block the IL-6 signal, and tocilizumab, a humanized monoclonal antibody against human IL-6 receptor, has been the most intensively studied agent for clinical use. A series of clinical trials of tocilizumab have demonstrated the robustness of safety and efficacy of tocilizumab in the treatment of patients with above diseases. In this review, targeting IL-6 actions as an immunotherapy is discussed.
18460270 Consensus procedures and their role in pediatric rheumatology. 2008 Apr The Delphi Technique and Nominal Group Technique are two well-recognized consensus-formation methodologies specifically designed to combine judgments from a group of experts. The Delphi Technique utilizes a series of well-defined questionnaire-based surveys, whereas Nominal Group Technique is a structured face-to-face meeting designed to facilitate consensus. Consensus-formation techniques require that each step build on the results of the previous steps. In this review, we describe these techniques, how they work, and their practical application in pediatric rheumatology, where they have been widely used to develop the outcome measures of several chronic rheumatic diseases, including juvenile idiopathic arthritis, rheumatoid arthritis, systemic lupus erythematosus, and idiopathic inflammatory myopathies, as well as the classification criteria for juvenile systemic sclerosis and juvenile vasculitides.
16863964 Laser in situ keratomileusis in patients with autoimmune diseases. 2006 Aug PURPOSE: To evaluate the safety of laser in situ keratomileusis (LASIK) in patients with autoimmune diseases. SETTING: Private clinical practice. METHODS: In this retrospective case series, the records of patients who had LASIK at the Maloney Vision Institute between June 1, 1998, and October 1, 2004, were reviewed for a history of autoimmune disease including systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, scleroderma, inflammatory bowel disease, Graves' disease, Reiter's syndrome, and Hashimoto's disease. The records were reviewed for corneal and scleral complications of autoimmune disease after LASIK. RESULTS: Forty-nine eyes of 26 patients with inactive or stable autoimmune disease were identified. No eye developed corneal thinning, melting, persistent epithelial defect, persistent keratitis, scleral thinning, scleritis, or scleromalacia. CONCLUSION: Laser in situ keratomileusis may be a reasonable option in patients with well-controlled or inactive autoimmune disease.
16724810 Genetics of autoimmune diseases: a multistep process. 2006 It has so far been difficult to identify genes behind polygenic autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), and type I diabetes (T1D). With proper animal models, some of the complexity behind these diseases can be reduced. The use of linkage analysis and positional cloning of genes in animal models for RA resulted in the identification of one of the genes regulating severity of arthritis in rats and mice, the Ncf1 gene. The Ncf1 gene encodes for the Ncf1 protein that is involved in production of free oxygen radicals through the NADPH oxidase complex, which opens up a new pathway for therapeutic treatment of inflammatory diseases. In most cases, however, a quantitative trait locus (QTL) is the sum effect of several genes within and outside the QTL, which make positional cloning difficult. Here we will discuss the possibilities and difficulties of gene identification in animal models of autoimmune disorders.