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ID PMID Title PublicationDate abstract
15609168 Implementing standardized cost categories within economic evaluations in musculoskeletal d 2003 We present a matrix of relevant resource utilization domains for use in standardizing applied cost assessment in musculoskeletal conditions. In addition,we highlight the importance of selecting cost categories during the development of an economic evaluation. A set of four steps was applied: (a) literature search identifying economic evaluations in osteoarthritis and osteoporosis, (b) listing and aggregation of cost categories mentioned in the identified articles, (c) development of a matrix of resource utilization domains, and (d) qualitative discussion regarding the generalizability of the matrix to other musculoskeletal conditions such as rheumatoid arthritis. We examined 41 full-length articles (25 cost-of-illness studies or cost-comparisons, 14 cost-effectiveness analyses, and 2 cost-utility analyses), of which 16 studies focused on osteoarthritis and 25 on osteoporosis. The reviewed studies used a total of 151 different cost categories which, after adjustment for synonymous labeling, made up 34 cost categories. A matrix of 16 separate resource utilization domains was developed including seven outpatient, three inpatient, four other disease-related, and two productivity cost domains. We found that cost assessment in economic evaluation in the key musculo-skeletal diseases (osteoarthritis, osteoporosis, and rheumatoid arthritis) is performed rather inhomogeneously. A generalized matrix of applicable resource utilization domains and a flowchart facilitating the development of appropriate resource utilization data have been developed.
14979927 Evidence for early disease-modifying drugs in rheumatoid arthritis. 2004 Some research evidence supports early aggressive treatment of rheumatoid arthritis (RA) using combination therapy with two or more disease modifying anti-rheumatic drugs (DMARDs) plus steroids, or even DMARDs plus an anti-TNF. By contrast, conservatively delayed DMARD monotherapy, given after non-steroidal anti-inflammatory drugs have failed, has been criticised. However, recent long-term studies highlight the complexities in evaluating whether to abandon pyramidal treatment in favour of early DMARDs. Although patients given early DMARD therapy show short-term benefits, longer-term results show no prolonged clinical advantages from early DMARDs. By 5 years patients receiving early DMARDs had similar disease activity and comparable health assessment questionnaire scores to patients who received DMARDs later in their disease course. X-ray progression was persistent and virtually identical in both groups. These negative findings do not invalidate the case for early DMARD therapy, as it is gives sustained reductions in disease activity in the early years of treatment without excessive risks from adverse effects. However, early DMARDs alone do not adequately control RA in the longer term. This may require starting with very aggressive therapy or treating patients more aggressively after early DMARD therapy has been initiated.
12587496 [Knee joint synovectomy in treatment of juvenile idiopathic arthritis]. 2002 PURPOSE OF THE STUDY: The objective of this study was to assess short-term outcomes of knee joint synovectomy in a group of patients with juvenile rheumatoid arthritis and to present the authors' view on this approach. MATERIAL: Between 1990 and 1999, synovectomy of the knee joint was performed in a group of 46 children with juvenile rheumatoid arthritis. This group comprised 19 girls and 27 boys aged 4 to 16 years (mean 9.8 years) with all forms of the disease. A total of 85 synovectomy procedures, including repeat operations, were performed on 58 knee joints. METHODS: Arthroscopic synovectomy was used to treat 21 knee joints, open synovectomy from two approaches was indicated, as a primary procedure, in 37 knees. The assessment of subjective and functional conditions of patients was based on a modified rating systems of Lysholm and X-ray films were evaluated by the Larsen classification. The evaluation was carried out at 1 and 2 years after the primary operation. RESULTS: Articular lesions corresponding to mere synovitis were found in 10 knee joints (17.2%), a developing pannus without erosion was seen in 16 (27.6%) and erosion of the articular surface in 32 (55.2%) knee joints. At 1 year, the value of Lysholm's score rose from 47.9 to 84.3 points and was followed by a decrease to 73.2 at 2 years. Within 2 years of the primary operation, the condition recurred in 9 out of 21 knees (42.8%) treated by arthroscopic synovectomy and in 12 cases (32.4%) operated on by open synovectomy. The relapse was observed mostly in patients with an overall high inflammatory activity and polyarticular and systemic progression of the disease. DISCUSSION: We do not agree with the view of some authors that surgical intervention is not indicated until erosions are radiologically manifested. In children, erosions usually present at a late stage, as shown by 12 findings of articular surface destruction in our group that were not detected by radiography. For indication purposes, we distinguished between preventive and therapeutic synovectomy. We found a significant association between the overall activity and early recurrence of the disease. In 60.7% of the cases (28) with excellent outcomes, this activity was low at the time of surgery. On the other hand, in 75% of the cases (8) with poor outcomes, the activity of disease was very high and had a lasting tendency to recur. These findings are in agreement with the conclusions of several other authors who consider the presence of systemic disease to be a contraindication for synovectomy. Advantages of arthroscopic synovectomy reported in adult patients seem to be relative in children. A good view of and accessibility to individual articular components, which are made an advantage of in the adult knee, are rather exceptional in the "tight" child knee. The evaluation of our patients at a short-term follow-up did not give convincing results although the early effect of synovectomy was very good. The poor outcomes seen in our group, which corresponded with observations of other authors, allow us to learn more about the potentials of synovectomy and thus to promote our policy of a thorough consideration of indications for surgery. CONCLUSION: Indications for surgical treatment in patients with juvenile rheumatoid arthritis are evaluated in cooperation with a rheumatologist after an appropriate conservative therapy administered for at least 6 months. Cases with clear signs of plastic synovitis and skeletal lesions shown by radiography as well as all recurrent conditions are treated by open synovectomy. The state of low disease activity is preferred for surgical intervention. It has to be borne in mind that, from whole range of curative procedures, conservative therapy supervised by a pediatric rheumatologist is the method of choice.
15341657 Comparison of the NEI-VFQ and OSDI questionnaires in patients with Sjögren's syndrome-rel 2004 Sep 1 BACKGROUND: To examine the associations between vision-targeted health-related quality of life (VT-HRQ) and ocular surface parameters in patients with Sjögren's syndrome, a systemic autoimmune disease characterized by dry eye and dry mouth. METHODS: Forty-two patients fulfilling European / American diagnostic criteria for Sjögren's syndrome underwent Schirmer testing without anesthesia, ocular surface vital dye staining; and measurement of tear film breakup time (TBUT). Subjects were administered the Ocular Surface Disease Index (OSDI) and the 25-item National Eye Institute Vision Functioning Questionnaire (NEI-VFQ). Main outcome measures included ocular surface parameters, OSDI subscales describing ocular discomfort (OSDI-symptoms), vision-related function (OSDI-function), and environmental triggers, and NEI-VFQ subscales. RESULTS: Participants (aged 31-81 y; 95% female) all had moderate to severe dry eye. Associations of OSDI subscales with the ocular parameters were modest (Spearman r (rho) < 0.22) and not statistically significant. Associations of NEI-VFQ subscales with the ocular parameters reached borderline significance for the near vision subscale with TBUT (rho = 0.32, p =.05) and for the distance vision subscale with van Bijsterveld score (rho = 0.33, p =.04). The strongest associations of the two questionnaires were for: ocular pain and mental function with OSDI-symptoms (rho = 0.60 and 0.45, respectively); and general vision, ocular pain, mental function, role function, and driving with OSDI-function (rho = 0.60, 0.50, 0.61, 0.64, 0.57, and 0.67, respectively). CONCLUSIONS: Associations between conventional objective measures of dry eye and VT-HRQ were modest. The generic NEI-VFQ was similar to the disease-specific OSDI in its ability to measure the impact of Sjögren's syndrome-related dry eye on VT-HRQ.
15607091 Quantification of dynamic contrast-enhanced MR imaging of the knee in children with juveni 2004 Nov Improved management of arthritis requires a reliable, quantifiable, noninvasive method to monitor the degree of inflammation and therapeutic response during the early phase of the disease. For this purpose, the uptake of Gd-DTPA in the distal femoral physis and synovium in children with juvenile rheumatoid arthritis (JRA) was evaluated with a two-compartment pharmacokinetic model and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Employing a two-compartment pharmacokinetic model, the theoretical signal enhancement from Gd-DTPA enhanced dynamic 3D gradient-recalled echo (GRE) images was shown to have a simple linear relationship with tissue concentration independent of flip angle. The signal-enhancement patterns for each individual knee were found to be characterized by three pharmacokinetic parameters: k(ep) (min(-1)), the rate constant; k(el) (min(-1)), the elimination rate constant; and E(R) (min(-1)), the initial enhancement rate, which is proportional to the transfer constant K(trans) (min(-1)). Characteristic patterns were observed in the image signal intensity-time course. The initial enhancement rate, E(R), in regions of interest (ROIs) was found to have a wide range of variation: 5 to 38 min(-1) over the distal femoral physis and 1 to 10 min(-1) in the synovium. The E(R) of the synovium was correlated with the E(R) of the distal femoral physis (P<.05). In addition, the E(R) of the synovium was correlated to the clinical outcome measures of knee swelling. Further investigation is needed to determine whether wide variations in the pharmacokinetic parameters reflect the degree of disease activity, and whether there are changes in response to therapy. This method can also be applied in adults with rheumatoid arthritis (RA) and other disorders where T(1)-weighted contrast is used (breast cancer, brain tumors).
12719998 Pseudotumor cerebri associated with Sjögren's syndrome. 2003 Apr PURPOSE: To report a case of papilledema and pseudotumor cerebri developed in association with Sjögren's syndrome. METHODS: Case-report of a 38-year-old woman with history, imaging and histology confirming the diagnosis of both pseudotumor cerebri and Sjögren's syndrome who presented with bilateral decrease of vision. RESULTS: Papilledema associated with pseudotumor cerebri was observed in both eyes. The patient's visual acuity improved transiently with the administration of intravenous steroids and cyclophosphamide; subsequently she needed a ventriculoperitoneal shunt. CONCLUSION: Sjögren's syndrome should be considered in the different etiologies of pseudotumor cerebri. The major improvement with corticosteroids and ventriculoperitoneal shunt makes prompt diagnosis essential.
12232573 Lymph node lesion in adult-onset Still's disease resembling peripheral T-cell lymphoma: a 2002 Jul Adult-onset Still's disease (AOSD) is known to be a cause of fever of unknown origin. We describe the clinicopathologic, immunohistologic, and genotypic features of 3 patients with lymph node lesions from AOSD, which posed a serious diagnostic difficulty from peripheral T-cell lymphomas. The patients were 22-, 26-, and 63-year-old Japanese women. At the onset of disease, all patients had multicentric lymphadenopathy in association with clinical and laboratory findings suggestive of a malignant lymphoma. None of the patients developed malignant lymphomas during the follow-up period. Histologically, the lesions were characterized by paracortical hyperplasia with prominent vascular proliferation. In the paracortical area, there was a mixed infiltrate including small-to-medium-sized lymphocytes, variable numbers of eosinophils, plasma cells, and B immunoblasts. Polymerase chain reaction analysis demonstrated that neither clonal rearrangement of the T-cell receptor gamma-chain gene nor immunoglobulin heavy-chain rearrangement was detected in any patient. Although AOSD appears to be a rare systemic inflammatory disorder, the lymph node lesion should be added to the differential consideration of benign lymph node lesions simulating node-based peripheral T-cell lymphoma.
12092302 [Clinical thinking and decision making in practice. A young woman with fever, arthralgia a 2002 Jun 15 A 19-year-old woman was admitted because of high fever, rash, arthralgia and sore throat. On physical examination a diffuse skin rash was observed, leaving a facial mask unaffected. C-reactive protein and erythrocyte sedimentation rate were raised (114 mg/l and 26 mm in the first hour, respectively); white blood cell count was normal (6.2 x 10(9)/l) with an increased count of immature forms. An infective, metabolic or haematological cause was excluded. Serum ferritin turned out to be extremely elevated (4318 micrograms/l), so adult-onset Still's disease was diagnosed. The patient fulfilled the criteria of Cush et al. for adult-onset Still's disease. She was first treated with non-steroidal anti-inflammatory drugs (NSAIDs) and, at a later stage in the disease, with corticosteroids. All symptoms disappeared and blood test results normalised.
14740169 Varicella glomerulonephritis mimicking microscopic polyangiitis. 2004 Nov Varicella in childhood is usually a self-limiting illness with few complications. Varicella nephritis is an uncommon entity and seen mostly in immunocompromized individuals. We report a 14-year-old boy with juvenile rheumatoid arthritis who developed varicella nephritis and in whom the renal manifestations preceded the skin lesions by 1 week. This is an extremely unusual occurrence, and only one case has been described before. Such a presentation can mimic the clinical features of microscopic polyangiitis.
15527702 The role of immune tolerance in preventing and treating arthritis. 2004 Dec It has become increasingly clear that the innate and adaptive arms of the immune response cooperate in generating autoimmune damage in the pathogenesis of rheumatoid arthritis and juvenile idiopathic arthritis. Treatment targets the immunologic pathophysiology of the disease and is based on regaining immune tolerance. Recently introduced biological agents neutralize or simply block cytokines and their proinflammatory pathways, with favorable clinical outcome. However, major downsides are their lack of specificity and the need of continuous administration to be effective. Possibly, more can be gained from a specific approach. Indeed, recent findings suggest that targeting antigen-specific T cells can reinstate regulatory mechanisms and thus induce immune tolerization. This improved understanding has paved the way to novel immunotherapeutic approaches, some of which will be discussed here.
15142260 Altered signalling thresholds in T lymphocytes cause autoimmune arthritis. 2004 The development of spontaneous autoimmunity in inbred strains of rodents has allowed us to investigate the molecular basis of chronic inflammatory disease in ways that would not be possible in humans. Recently, two new mouse models of autoimmune inflammatory polyarthritis have been reported that demonstrate how alterations in signalling thresholds sufficient to perturb central T-cell tolerance lead to inflammatory arthritis. These mice provide new insights into the complexities of what may turn out to be a heterogeneous group of diseases that we call rheumatoid arthritis. They will also provide unique tools for dissecting precisely how chronically activated T cells contribute to the effector phase of arthritis through mechanisms that may be less dependent on antigen receptor signalling.
11819063 Mega os trigonum in progressive pseudorheumatoid dysplasia. 2002 Jan BACKGROUND: Progressive pseudorheumatoid dysplasia (PPRD), a noninflammatory condition, needs to be differentiated diagnostically from juvenile rheumatoid arthritis (JRA). OBJECTIVE: Demonstration of an unusually large and often early-appearing os trigonum helps distinguish PPRD from JRA. MATERIALS AND METHODS: Ankle images in four children with PPRD were reviewed. RESULTS: The os trigonum was abnormally enlarged in all PPRD subjects and was shown to have appeared or fused earlier than normal in two subjects. CONCLUSION: A large and early os trigonum ossification helps differentiate PPRD from JRA.
15188369 Juvenile rheumatoid arthritis affected sibpairs: extent of clinical phenotype concordance. 2004 Jun OBJECTIVE: To investigate the clinical phenotypes and demographic characteristics of 183 affected sibling pairs (ASPs) with juvenile rheumatoid arthritis (JRA) and to determine whether there are differences between the clinical phenotypes of the ASP cohort compared with patients with sporadic disease and whether there is greater sharing of specific clinical features within versus between sibpairs. METHODS: Details of the JRA Affected Sibpair Registry operations have been described previously. The frequencies of phenotypes in the 2 cohorts were tabulated, summary statistics were determined, and comparisons were made by chi-square test or t-test. Sibling risk, sibling risk ratios (lambda(s)), and odds ratios were calculated to assess familial aggregation of several different clinical manifestations. RESULTS: The most common onset type among the 164 nontwin ASPs was pauciarticular (65% overall). Fifty-three percent of the ASPs were concordant for pauciarticular-onset JRA; 19% were concordant for a polyarticular disease onset. Among subjects with polyarticular-onset disease, significantly more joints were involved at onset in simplex patients than in ASPs (P = 0.008). The difference in age at JRA onset within sibpairs (sibling 1 versus sibling 2) was not significantly different. ASPs developed disease at a mean real-time difference of 5.1 years apart. Familial aggregation was found for tenosynovitis (lambda(s) 29.5), leukocytosis (lambda(s) 25), rheumatoid factor (lambda(s) 11.0), anemia (lambda(s) 1.7), and antinuclear antibodies (lambda(s) 1.3). CONCLUSION: This study confirms the findings of earlier studies showing that a high proportion of ASPs overall show concordance of disease-onset type, except for the subset of patients with systemic disease, and that nontwin ASPs do not develop disease at the same point in real time. We conclude that JRA and its clinical manifestations do not differ substantially between ASPs and the simplex population. The exception is the number of affected joints at JRA onset among patients with polyarticular-onset disease. Familial aggregation of clinical features among ASPs adds strong evidence for a genetic background in this disease.
24387248 Total knee arthroplasty for rheumatoid arthritis. 2003 Dec Abstract Total knee arthroplasty is a proven technique for the management of deformity and unremitting pain in the rheumatoid arthritic knee. Many important considerations must be taken into account in order to maximize the results of total knee replacement in this challenging patient population.
16819033 [Congenital deficiency of coagulation factor VII in an Icelandic family.]. 2004 May Congenital deficiency of coagulation factor VII is a rare autosomal and usually recessive genetic bleeding disorder which has been discovered in an Icelandic family. The propositus is a male who experienced intermittent painful inflammation of his ankle joints at the age of 9-10 and later also in his knees, elbow, shoulder, and wrist. Smaller joints were spared, serologies for rheumatoid disease were negative. He was treated for rheumatoid arthritis with limited results and became practically invalid due to his arthritis at the age of 40. At the age of 57, a surgical synovectomy of his knee joint was complicated by postoperative bleeding, and signs of chronic haemorrhagic arthritis were noted in the synovia. Subsequently, a marked prolongation of his prothrombin time and a near total deficiency of coagulation factor VII were discovered. All of his nine siblings were deficient in coagulation factor VII, three of them markedly deficient like the proband and six moderetely deficient. The pattern of inheritance suggests that one of their parents was heterozygous and the other homozygous or doubly heterozygous of genetic deficiency of coagulation factor VII. The parents were second cousins. Of the siblings, only the propositus had a bleeding tendency or arthritis. No evidence of such symptoms in their parents or grandparents was found. This family is the only Icelandic family with congenital deficiency of coagulation factor VII known to the authors.
14723486 Low levels of anti-histone antibodies in north Indian children with juvenile rheumatoid ar 2003 Nov BACKGROUND & OBJECTIVES: Early onset pauciarticular disease with uveitis is distinctly uncommon in Indian children with juvenile rheumatoid arthritis (JRA). The occurrence of anti-histone antibodies (AHA) in serum is strongly associated with presence of uveitis. There is a paucity of information from India on the levels of AHA in patients of JRA. In this study, an attempt was made to evaluate the levels of IgG and IgM antibodies to histones in children with JRA in north India. METHODS: Serum samples of 148 children with JRA (84 boys, 64 girls) were collected. Clinical details including onset, symptoms and course of the disease in each patient were recorded. Detailed eye examination including slit lamp examination was done in all patients at presentation and yearly thereafter to rule out uveitis. The presence of antihistone IgG and IgM antibodies was studied by ELISA. Antinuclear antibodies (ANA) were measured by indirect immunofluorescence using HEP-2 cells as substrate at a screening dilution of 1:40. RESULTS: Of the 148 children, 54 had pauciarticular (12 early onset and 42 late onset), 64 polyarticular and 30 systemic onset disease respectively. ANA were present in two children. AHA were raised in 15 (10%) children, of whom 10 had IgM antibodies, 3 had IgG and 2 had both isotypes. None of the children with early onset pauciarticular disease had uveitis, ANA or AHA. INTERPRETATION & CONCLUSION: The low occurrence of AHA and uveitis in our subset of patients with JRA is in contrast to that reported from Western countries. The low occurrence is unlikely due to technical reasons as the antigen that has been used consistently showed significant binding to serum from patients with systemic lupus erythematosus (SLE). This is in accordance with the rarity of early onset pauciarticular disease and chronic uveitis in these patients. More studies from other parts of the country are required to validate this observation.
12506279 Time of onset of uveitis in children with juvenile rheumatoid arthritis. 2002 Dec BACKGROUND: Recently, it has been advocated to decrease the frequency of eye examinations to screen for uveitis in children with juvenile rheumatoid arthritis (JRA) because of the low yield of positive findings after an initial normal eye examination. This study was undertaken to determine the time interval for the development of uveitis after the diagnosis of JRA and to further describe patients who develop uveitis related to JRA. METHODS: This was a retrospective chart review of all patients with JRA examined by either of 2 pediatric ophthalmologists from August 1984 to June 2001. All patients were also under the care of the Pediatric Rheumatology Division at Schneider Children's Hospital. Age of diagnosis of JRA, disease onset subtype of JRA, antinuclear antibody titers, age of diagnosis of uveitis, and complications from uveitis were recorded. RESULTS: One hundred fifty eight patients with JRA had eye examinations; 39 (25%) developed uveitis. Sixteen patients had uveitis on the initial eye examination, and 23 subsequently developed uveitis. When uveitis was absent at the initial eye examination, the mean time to develop it was 20 months (range, 4-81 months). CONCLUSIONS: A normal initial eye examination does not preclude the development of uveitis in patients with JRA. We recommend continuing the current standards of ophthalmologic examinations to screen for uveitis in children with JRA as prescribed by the Section on Rheumatology and Ophthalmology of the American Academy of Pediatrics.
11841481 Prevalence of human leukocyte antigen (HLA) DRB1 alleles in Kuwaiti children with juvenile 2002 Feb The prevalence of human leukocyte antigen (HLA) DR alleles has been determined in 69 Kuwaiti Arab children with juvenile rheumatoid arthritis (JRA) and compared to that in 212 ethnically matched normal healthy controls using a PCR-sequence specific primers (PCR-SSP) method. A very high incidence of DR3 was detected in JRA patients compared to the controls (P < 0.0001, RR = 2.235). The high incidence of HLA-DR3 in JRA patients was accounted for mainly by an excess of DRB1*0307 (P < 0.05, RR = 3.072) and DRB1*0308 (P < 0.009, RR = 2.663) compared to the controls. Moreover, DR3 was more prevalent when patients with ANA-positive JRA were analysed separately; 73% compared to 58% for the whole JRA patient group. The frequency of DR1 was also higher in the JRA group compared to controls (P = 0.019, RR = 3.585). Although the incidence of some alleles was higher in the control group (DR13 and DR7), none reached a statistically significant level. All the patients with iridocyclitis had either a DR1 or DR3 allele, except for one child. The frequency of DRB1*03 was found to be much higher in the polyarticular subtype of Kuwaiti JRA cases compared to the oligoarticular subgroup and the controls. Also, a non-significant increase in the frequency of the DRB1*04, *11 and *15 alleles was detected in the polyarticular subtype of the Kuwaiti JRA cases compared to the controls.
15319795 Etoricoxib. 2004 May Etoricoxib (Arcoxia, Merck & Co., Inc.) is a selective inhibitor of cyclooxygenase-2 (COX-2), an enzyme involved in pain and inflammation. It is a member of the COX-2-selective (coxib) class of nonsteroidal antiinflammatory drugs (NSAIDs). Extensive clinical trials have confirmed its analgesic and antiinflammatory efficacy to be at least as good as and in some cases superior to nonselective NSAIDs in a number of disease and patient treatment settings. Etoricoxib displays improved gastrointestinal safety compared with nonselective NSAIDs and has a favorable overall safety and tolerability profile. It is rapidly and completely absorbed following oral administration providing a rapid onset of action. Its long plasma half-life allows for once-daily dosing. Etoricoxib is currently approved in a number of countries for various indications including the treatment of acute pain, acute gouty arthritis, chronic low back pain, primary dysmenorrhea, and chronic treatment for the signs and symptoms of osteoarthritis and rheumatoid arthritis. In countries where it is approved, the highest recommended daily dose for chronic use is 90 mg for rheumatoid arthritis and 60 mg for osteoarthritis and chronic low back pain. The recommended daily dose for acute pain relief treatment from primary dysmenorrhea and acute gouty arthritis is 120 mg. This review summarizes the published preclinical and clinical data relevant to the use of etoricoxib in clinical practice.
14500645 Genetic control of tolerance to type II collagen and development of arthritis in an autolo 2003 Oct 1 T cell recognition of the type II collagen (CII) 260-270 peptide is a bottleneck for the development of collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. We have earlier made C3H.Q mice expressing CII with glutamic acid instead of aspartic acid at position 266 (the MMC-C3H.Q mouse), similar to the rat and human CII epitope, which increases binding to MHC class II and leads to effective presentation of the peptide in vivo. These mice show T cell tolerance to CII, but also develop severe arthritis. The present investigation shows that non-MHC genes play a decisive role in determining tolerance and arthritis susceptibility. We bred MMC into B10.Q mice, which display similar susceptibility to CIA induced with rat CII as the C3H.Q mice. In contrast to MMC-C3H.Q mice, MMC-B10.Q mice were completely resistant to arthritis. Nontransgenic (B10.Q x C3H.Q)F(1) mice were more susceptible to CIA than either of the parental strains, but introduction of the MMC transgene leads to CIA resistance, showing that the protection is dominantly inherited from B10.Q. In an attempt to break the B10-mediated CIA protection in MMC-transgenic mice, we introduced a transgenic, CII-specific, TCR beta-chain specific for the CII(260-270) glycopeptide, in the highly CIA-susceptible (B10.Q x DBA/1)F(1) mice. The magnification of the autoreactive CII-specific T cell repertoire led to increased CIA susceptibility, but the disease was less severe than in mice lacking the MMC transgene. This finding is important for understanding CIA and perhaps also rheumatoid arthritis, as in both diseases MHC class II-restricted T cell recognition of the glycosylated CII peptide occurs.