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ID PMID Title PublicationDate abstract
15784628 Increased stiffness of the abdominal aorta in women with rheumatoid arthritis. 2005 Jul OBJECTIVE: To study the distensibility and the diameter of the abdominal aorta and the common carotid artery (CCA) in patients with rheumatoid arthritis (RA), and investigate the relation between mechanical properties of these arteries and disease severity. METHODS: One hundred and one patients with RA (33 consecutive cases with extra-articular manifestations, and 68 subjects with non-extra-articular disease, matched for age, sex and disease duration) were investigated. Echo-tracking ultrasonography was used to measure stiffness and mean diameter of the abdominal aorta and the CCA. The patients were compared with healthy individuals from the corresponding age group (n=74 for measurements of the aorta, n=64 for the CCA). Predicted values for stiffness and mean diameter, based on age and sex, were calculated. RESULTS: Stiffness of the abdominal aorta was increased in women with RA [mean percentage of predicted value (% predicted) 180; 95% confidence interval (95% CI) 150-211] but not in men (% predicted 99; 95% CI 75-122). CCA stiffness was less markedly increased, and mean diameters of the aorta and the CCA were not different from the expected. In the RA cohort, patients with extra-articular manifestations tended to have greater stiffness of the aorta (P=0.11), and disability, as indicated by a higher Health Assessment Questionnaire score, was associated with increased aortic stiffness (P=0.04). CONCLUSION: RA is associated with decreased distensibility of the abdominal aorta in females, and such changes seem to correlate with disease severity. We suggest that arterial stiffness is an important factor in cardiovascular co-morbidity in RA.
16232091 Efficacy of three ELISA measurements of anti-cyclic citrullinated peptide antibodies in th 2005 The objective of the present study was to determine the efficacy of anti-cyclic citrullinated peptide (anti-CCP) antibody detection in the early diagnosis of rheumatoid arthritis (RA), as well as to compare three commercially available enzyme-linked immunosorbent assay (ELISA) kits used to detect such antibodies. We analysed the presence of anti-CCP antibodies in the sera of 78 patients who had been newly referred from primary healthcare centres to the Early Polyarthritis Unit. We also included in the study a group of 50 healthy controls. None of the patients had previously received treatment for the disease. After 1-year follow-up, the diagnosis of RA was confirmed in 53 of these patients. The ELISA kits under study were IMMUNOSCAN RA (Euro-Diagnostica AB), QUANTA Lite CCP IgG ELISA (INOVA Diagnostic) and DIA-STAT Anti-CCP (Axis-Shield Diagnostics); the sensitivity obtained was 52.8%, 58.5% and 52.8%, respectively, with 100% specificity for all three kits. Anti-CCP antibodies detected the presence of RA in 26% of patients without positive rheumatoid factor (RF). The sum of anti-CCP antibodies or the presence of RF gave a sensitivity of up to 67%, with specificity ranging between 94 and 97%. Anti-CCP antibodies show high specificity for the diagnosis of RA. The three ELISAs analysed offer the same degree of diagnostic accuracy.
16265684 The predictive value of rheumatoid factor isotypes, anti-cyclic citrullinated peptide anti 2005 Nov OBJECTIVE: To evaluate the significance of rheumatoid factor (RF) and its isotypes (IgA RF, IgG RF, and IgM RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), and antineutrophil cytoplasmic antibodies (ANCA) in predicting mortality in patients with rheumatoid arthritis (RA). METHODS: The study population comprised 604 patients with RA participating in a cross-sectional study in 1987. Presence of RF (n = 604), RF isotypes (n = 206), anti-CCP (n = 184), and ANCA (n = 200) were determined in these patients from available baseline sera. Vital status was assessed in 1999 and multivariate Cox regression analysis used to compare mortality in RA patients with or without different antibodies. RESULTS: Of the 604 patients with RA, 55% were positive for RF, 66% for anti-CCP, and 14.5% for perinuclear ANCA. Twelve patients (19%) with RF were anti-CCP-negative and 34 (40%) without RF were anti-CCP-positive. Of the total 604 patients, 160 had died by 1999. Positive RF and high IgA and IgM RF levels predicted increased mortality, while positive anti-CCP or ANCA did not. However, high anti-CCP levels were related to an increased mortality risk. CONCLUSION: Patients with RA with positive RF, especially IgA and IgM isotypes, carry a risk of dying earlier than patients without these serological findings.
17294867 [Prognostic value of some serological markers of rheumatoid arthritis in assessment of x-r 2006 AIM: To specify significance of some serological markers for diagnosis and x-ray prognosis of rheumatoid arthritis (RA). MATERIAL AND METHODS: A total of 115 RA patients with the disease history not longer than 4 years were examined for serum antibodies to cyclic citrullated peptide (ACCP), rheumatoid factor (RF), antikeratine antibodies (AKA) using enzyme immunoassay and indirect immunofluorescence. RESULTS: ACCP, AKA, IgA-RF, IgM-RF were detected in 79.15%, 47.8%, 64.3%, 89.6% patients, respectively. ACCP was found to be directly correlated with negative x-ray changes in hand and foot joints. ACCP specificity reached 97%, the highest specificity (up to 100%) being in determination of RF and ACCP. CONCLUSION: ACCP is an independent factor increasing significance of x-ray indices and thus allowing prognosis of x-ray outcome of RA.
15818715 Need for information and for involvement in decision making among patients with rheumatoid 2005 Apr 15 OBJECTIVE: To measure the need for information about rheumatoid arthritis (RA) and the level of desire for involvement in treatment decisions among patients with RA. To examine the relationship between these preferences and what factors (sociodemographic, disease, treatment, level of disability, and level of knowledge about RA) associate with these preferences. METHODS: Questionnaire surveys were mailed to a randomly selected group of 600 patients with RA. Need for information and desire for involvement in decision making were measured using a validated tool (the Autonomy Preference Index). RESULTS: The response rate was 57.3%. The need for information was very high. Information seeking preference scores (median 82.5, interquartile range 80.0-92.5) were significantly higher (P < 0.001) than decision making preference scores (mean +/- SD 56.4 +/- 13.6). Need for information and for decision making were both higher in women than men, and associations with these needs differed in men and women. However, younger age and greater knowledge of RA predicted greater need for decision making. There was no correlation between need for information and for involvement in treatment decisions for either sex (women: r(s) = 0.09, P = 0.19; men: r(s) = -0.06, P = 0.54). CONCLUSION: There was a high level of need for information among patients with RA. Desire for involvement in treatment decision making was significantly lower and did not correlate with need for information. Associations with these needs differed for men and women.
15681242 The role of leukocyte-stromal interactions in chronic inflammatory joint disease. 2005 Jan Rheumatoid arthritis (RA) is a debilitating, chronic, persistent inflammatory disease that is characterised by painful and swollen joints. The aetiology of RA is unknown, however whereas past research has concentrated on the role of immune or inflammatory infiltrating cells in inflammation, it is becoming clear that stromal cells play a critical part in regulating the quality and duration of an inflammatory response. In this review we assess the role of fibroblasts within the inflamed synovium in modulating immune responses; in particular we examine the role of stromal cells in the switch from resolving to persistent inflammation as is found in the rheumatoid synovium.
16306475 Looking back: rheumatoid arthritis--aetiology, occurrence and mortality. 2005 Dec Kellgren and Lawrence performed the first studies of the incidence and prevalence of rheumatoid arthritis (RA) in the UK. These have since been updated in Norfolk. The current annual incidence is 36/100,0000 in women and 14/100,000 in men. The prevalence is 0.8% of the adult population. The incidence, prevalence and mortality of RA have fallen in women in the last 50 yr. Excess mortality is predominantly due to cardiovascular disease. Risk factors for the development of RA include obesity, smoking, high red meat consumption, a previous blood transfusion and an adverse pregnancy outcome. Protective factors include the oral contraceptive pill and adequate fruit intake.
16511921 Cervical spine surgery in patients with rheumatoid arthritis: longterm mortality and its d 2006 Mar OBJECTIVE: Atlantoaxial subluxation (AAS) is a frequent manifestation of rheumatoid arthritis (RA). The instability of the craniocervical junction caused by AAS is a potentially fatal condition and may require surgical treatment. Systemic manifestations associated with RA may increase the risk of perioperative complications. We evaluated the longterm mortality and its determinants in RA patients with AAS after cervical spine surgery. METHODS: A retrospective study of consecutive patients treated at Kuopio University Hospital between 1994 and 1998. Preoperative risk factors, neurological impairment using the Ranawat classification, perioperative course, functional outcome, and survival status were evaluated. RESULTS: During the study period 86 rheumatoid patients with AAS underwent cervical spine surgery. The mean followup time was 7.5 years (range 5.0-9.8). During the followup, 32 patients (37%) died. The mean survival time after surgery was 7.2 years (95% CI 6.7-8.0). Seven patients experienced postoperative complications. Age, AAS other than horizontal, and occurrence of complications were independent predictors of mortality. In two-thirds of the patients there was relief or decrease of pain, and the functional capacity improved. Neurological deficits subsided in 53% of cases. CONCLUSION: Patients with RA should be actively studied for AAS or other cervical instability, even when cervical symptoms are minor. Attention should be paid to perioperative management of these patients. Surgical treatment may not decrease the mortality of patients with RA, but it may result in more symptom-free life-years.
16920048 Autoimmune enteropathy and rheumatoid arthritis: a new association in the field of autoimm 2006 Dec We report the case of a 35-year-old woman with a diagnosis of coeliac disease at the age of 32 due to a severe malabsorption and flat mucosa without endomysial and tissue transglutaminase antibodies. The lack of clinical and histological improvement after 1 year of a gluten-free diet led to a diagnosis of refractory sprue. She had a good clinical response to steroids that were stopped after 3 months when she became pregnant. After delivery, she again started to complain of malabsorption with arthritis. Positivity for enterocyte autoantibodies together with a flat mucosa persistence allowed to identify a condition of autoimmune enteropathy; moreover, a rheumatological assessment gave evidence of an associated rheumatoid arthritis. Treatment by steroids and methotrexate brought to the remission of intestinal and articular symptoms together with an improvement of duodenal histology. This is the first description of an autoimmune enteropathy associated with rheumatoid arthritis. Autoimmune enteropathy should be always ruled out in patients with a villous atrophy unresponsive to a gluten-free diet, autoimmune manifestations and negativity of coeliac disease markers.
15927999 Infliximab does not activate replication of lymphotropic herpesviruses in patients with re 2005 Sep OBJECTIVE: The reactivation of human lymphotropic herpesviruses can be related to the intensity of immunosuppression. We analysed the risk of reactivation of lymphotropic herpesviruses in patients with refractory rheumatoid arthritis treated with an anti-tumour necrosis factor-alpha (TNF-alpha) agent (infliximab). METHODS: Fifteen patients were treated with infliximab (3 mg/kg) at weeks 0, 2 and 6. Samples of both plasma and peripheral blood mononuclear cells (PBMC) were obtained before treatment (week 0) and before each infusion at weeks 2 and 6. Samples were analysed using a multiplex qualitative polymerase chain reaction (PCR) for lymphotropic herpesviruses. Quantification of cytomegalovirus (CMV) viral load (copies/ml) was performed using quantitative PCR. Reactivation was defined as the presence of viral DNA in plasma. Latent infection was defined as the presence of viral DNA in PBMC samples but not in plasma. RESULTS: On baseline, latent CMV infection was detected in eight patients (53.3%), human herpesviruses-6 (HHV-6) in two (13.3%), Epstein-Barr virus (EBV) in seven (46.6%), CMV + HHV-6 in one (6.6%), CMV + EBV in two (13.3%) and HHV-6 + EBV in one (6.6%). Viral reactivation related to infliximab treatment was not observed. There was only one patient who had HHV-6 reactivation, but this was already detected in the baseline sample. CONCLUSIONS: Infliximab treatment does not induce replication of human lymphotropic herpesviruses in patients with rheumatoid arthritis. Thus, herpesviruses prophylaxis would not be indicated in these patients.
16740683 Work disability in early rheumatoid arthritis: higher rates but better clinical status in 2006 Dec OBJECTIVE: To analyse and compare work disability attributed to rheumatoid arthritis in two cohorts of patients with early disease: one in the US and the other in Finland. PATIENTS AND METHODS: Two cohorts of patients who were working and aged <65 years at the time of their first symptom of rheumatoid arthritis were studied: 269 patients in Nashville, TN, USA (median age 46 years, 72.5% females), and 364 patients from Jyväskylä, Finland, (median age 47.1 years, 70.9% females). The cohorts were analysed and compared for measures of clinical status and work disability status over a median (interquartile range) of 38.9 months in Nashville and 48.4 months in Jyväskylä. RESULTS: The probability of working at 36 months was 0.89 (0.84-0.92) for patients from Nashville and 0.84 (0.80-0.88) for patients from Jyväskylä (p = 0.02). These rates were lower than in earlier decades. Patients from Jyväskylä had significantly higher rates of work disability (p = 0.02) than those from Nashville, but better scores for self-report physical function (p<0.001), pain (p<0.001) and global status (p<0.001) at last observation. The likelihood of being disabled from work was 2.6-fold higher in Jyväskylä compared to Nashville (95% confidence interval 1.44 to 4.59, p = 0.001), after adjustment for demographic and disease-specific variables. CONCLUSION: Rates of work disability in both early rheumatoid arthritis cohorts were improved from earlier decades, but differed significantly in two different social systems. Higher work disability rates with better clinical status was seen in the Finnish early rheumatoid arthritis cohort than in the US cohort.
15720279 Soluble adhesion molecules in the pathogenesis of rheumatoid arthritis. 2005 Rheumatoid arthritis is chronic systemic inflammatory disease that is characterized by joint swelling and leukocyte recruitment into synovial tissue. Within the peripheral blood and synovial fluid of patients with rheumatoid arthritis there are many soluble mediators that function together to create an inflammatory environment ultimately responsible for the synovial pannus formation and subsequent joint destruction. One such group of soluble mediators present in the peripheral blood and synovial fluid of rheumatoid arthritic patients are soluble adhesion molecules. Soluble adhesion molecules are commonly formed as the result of cell surface adhesion molecule shedding due to cell stimulation, but may also be the result of de novo synthesis of truncated soluble forms of adhesion molecules. There has been debate over the function of soluble adhesion molecules in the inflammatory process. Soluble adhesion molecules have been shown to both enhance and inhibit different aspects of the inflammatory process. However, the preponderance of research studying rheumatoid arthritis has shown soluble adhesion molecules to be important regulators of leukocyte recruitment into the synovial tissue. This review will focus on the soluble adhesion molecules that have been studied in peripheral blood and synovial fluids of patients with rheumatoid arthritis. The role of different soluble adhesion molecules in the pathogenesis of rheumatoid arthritis will be discussed, as will the effects of common disease modifying anti-rheumatic therapies on their production.
15872306 Listeria-associated arthritis in a patient undergoing etanercept therapy: case report and 2005 May Listeriosis can be a cause of infectious arthritis. Here, we present a case of articular listeriosis in a patient with rheumatoid arthritis receiving treatment with etanercept, a tumor necrosis factor antagonist. We review the literature of articular listeriosis and discuss the role of tumor necrosis factor blockade in precipitating listeriosis.
16859518 Synovial fluid leukocyte apoptosis is inhibited in patients with very early rheumatoid art 2006 Synovial leukocyte apoptosis is inhibited in established rheumatoid arthritis (RA). In contrast, high levels of leukocyte apoptosis are seen in self-limiting crystal arthritis. The phase in the development of RA at which the inhibition of leukocyte apoptosis is first apparent, and the relationship between leukocyte apoptosis in early RA and other early arthritides, has not been defined. We measured synovial fluid leukocyte apoptosis in very early arthritis and related this to clinical outcome. Synovial fluid was obtained at presentation from 81 patients with synovitis of < or = 3 months duration. The percentages of apoptotic neutrophils and lymphocytes were assessed on cytospin preparations. Patients were assigned to diagnostic groups after 18 months follow-up. The relationship between leukocyte apoptosis and patient outcome was assessed. Patients with early RA had significantly lower levels of neutrophil apoptosis than patients who developed non-RA persistent arthritis and those with a resolving disease course. Similarly, lymphocyte apoptosis was absent in patients with early RA whereas it was seen in patients with other early arthritides. The inhibition of synovial fluid leukocyte apoptosis in the earliest clinically apparent phase of RA distinguishes this from other early arthritides. The mechanisms for this inhibition may relate to the high levels of anti-apoptotic cytokines found in the early rheumatoid joint (e.g. IL-2, IL-4, IL-15 GMCSF, GCSF). It is likely that this process contributes to an accumulation of leukocytes in the early rheumatoid lesion and is involved in the development of the microenvironment required for persistent RA.
16855136 The impact of stressors on health status and hypothalamic-pituitary-adrenal axis and auton 2006 Jun The hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are critically involved in inflammation and are activated by stress. This suggests that stressful circumstances may affect the chronic inflammation of rheumatoid arthritis (RA). Fifty-six scientific publications of the past 15 years were reviewed to get insight into the possible impact of stressors (grouped in five categories) on the health status and HPA axis and ANS functioning of adult patients with RA. Our findings in this review were: (1) In response to mental and physical effort and applied physiological stressors, patients demonstrate ANS hyporesponsiveness and "too normal" HPA axis responsiveness considering the elevated immune activity. A premorbid defect, past and current inflammatory activity, past and current stress, and physical deconditioning may explain disturbed physiological responses. (2) After brief naturalistic stressors, self-perceived and clinician's ratings of disease activity are increased; inflammation parameters have been insufficiently examined. (3) Major life events do not univocally affect disease status, but appear able to modify disease activity in a positive or negative way, depending on the nature, duration, and dose of the accompanying physiological stress response. (4) Enduring (e.g., work-related or interpersonal) stressors are associated with perceived health. Because this stressor category mingles with personality variables, the mere observation of a correlation does not prove that chronic stressors provoke health changes, although this might be the case. (5) Not one study rigorously examined the prospective hypothesis that past stressors (e.g., childhood victimization or pre-onset stressful incidents) may trigger RA or aggravate existing RA, which is a realistic belief for some patients.
15737255 Arthrodesis compared to Mayo resection of the first metatarsophalangeal joint in total rhe 2005 Feb BACKGROUND: Painful forefoot deformity from rheumatoid arthritis can be treated with resection of the lesser metatarsal heads combined with either resection or arthrodesis of the first metatarsophalangeal (MTP) joint. METHODS: In a prospective, randomized study we compared arthrodesis of first MTP joint with Mayo resection as part of total forefoot reconstruction in patients with painful forefoot deformity from rheumatoid arthritis. The lesser metatarsal heads were resected and extensor tenotomy was done in all patients. Thirty-one patients were randomized to either the arthrodesis or resection group. RESULTS: After a mean followup of 36 (26 to 52) months, the median subjective satisfaction score was 96 points out of 100 in the resection group and 92 points in the arthrodesis group. Significant improvements in pain, handicap, and activity according to Foot Function Index (FFI) were found in both groups (p <0.001 except for handicap in resection group and activity in fusion group were p=0.02). There were no statistically significant differences between the groups in these measures, nor in the patients' willingness to have the procedure again. There were no recurrences of prominences or tenderness under the forefoot in either group and no recurrence of severe hallux valgus in the resection group. The arthrodeses healed in 93%. There was no higher risk for clinically relevant IP joint symptoms after arthrodesis. The operating time was significantly longer in the arthrodesis group but this was not linked to a higher wound infection rate. CONCLUSION: These results indicate that Mayo resection may still be a good choice for the first MTP joint in total forefoot reconstruction in patients with rheumatoid arthritis.
17194614 Clinical practice format for choosing a second-line disease modifying anti-rheumatic drug 2007 Jan BACKGROUND: The objective was to develop a clinical practice format for choosing a second-line disease-modifying anti-rheumatic drug (DMARD) after a 6-month course of a first-line DMARD in patients with early RA. METHODS: A panel of 34 experts selected treatment option from various scenarios using the Thurstone pairwise method. The experts had to choose between two proposed DMARDs without proposing other options. The scenarios were obtained using the three items: DAS28, rheumatoid factor status and radiographic structural damage. A sample of 240 among 480 scenarios for each expert was taken at random. Responses given by at least 20% of the experts were considered pertinent. RESULTS: Recommendations for choosing a second DMARD for early RA after failure of a 6-month course of a first-line DMARD were established according to 4 parameters: type of first-line DMARD, activity, RF status and radiographic joint damage. The results of this study suggest that in patients with early RA who fail a 6-month course of first-line DMARD therapy, the best options may be addition of corticosteroid when disease activity is moderate to high and switching to a biologic agent when further radiographic joint damage occurs, particularly in patients with positive tests for RF. CONCLUSION: Although our scenarios did not include step-up (add instead of substitute) strategies, except for corticosteroids, we feel that the format presented here can optimise the management of patients with early RA seen in clinical practice.
16142722 Antigen microarray profiling of autoantibodies in rheumatoid arthritis. 2005 Sep OBJECTIVE: Because rheumatoid arthritis (RA) is a heterogeneous autoimmune disease in terms of disease manifestations, clinical outcomes, and therapeutic responses, we developed and applied a novel antigen microarray technology to identify distinct serum antibody profiles in patients with RA. METHODS: Synovial proteome microarrays, containing 225 peptides and proteins that represent candidate and control antigens, were developed. These arrays were used to profile autoantibodies in randomly selected sera from 2 different cohorts of patients: the Stanford Arthritis Center inception cohort, comprising 18 patients with established RA and 38 controls, and the Arthritis, Rheumatism, and Aging Medical Information System cohort, comprising 58 patients with a clinical diagnosis of RA of <6 months duration. Data were analyzed using the significance analysis of microarrays algorithm, the prediction analysis of microarrays algorithm, and Cluster software. RESULTS: Antigen microarrays demonstrated that autoreactive B cell responses targeting citrullinated epitopes were present in a subset of patients with early RA with features predictive of the development of severe RA. In contrast, autoimmune targeting of the native epitopes contained on synovial arrays, including several human cartilage gp39 peptides and type II collagen, were associated with features predictive of less severe RA. CONCLUSION: Proteomic analysis of autoantibody reactivities provides diagnostic information and allows stratification of patients with early RA into clinically relevant disease subsets.
16897118 The evaluation of quality of life in fibromyalgia syndrome: a comparison with rheumatoid a 2007 May Musculoskeletal disorders are the most common causes of deterioration in quality of life (QOL). We in this study aimed to assess (1) the impact of fibromyalgia syndrome (FS) on QOL comparing with that of rheumatoid arthritis (RA) patients and control subjects and (2) the impact of these two musculoskeletal disorders on various components of QOL using SF-36 Health Survey. Thirty-five patients with RA, 30 patients with FS, and 30 voluntary control subjects were included in the study. The groups were comparable in terms of demographic characteristics. QOL was evaluated by using Short-Form (SF)-36 Health Survey in all study participants, and Fibromyalgia Impact Questionnaire (FIQ), which is a specific health-status instrument for FS, was used in FS patients. Physical functioning, physical role, social functioning, bodily pain, general health, vitality, emotional role, and mental health scores were significantly lower in RA and FS patients than in control subjects (p<0.05). The between-groups comparisons revealed that FS patients had significantly lower mental health scores than RA patients (49.87 vs 62.51, respectively), (p<0.001). Total FIQ score correlated significantly with physical functioning, physical role, and bodily pain in FS patients. All parameters of SF-36 Health Survey except for social functioning correlated significantly with some of the variables of FIQ. FS has a negative impact on QOL, like RA. Furthermore, mental health was more severely affected in FS patients when compared with RA patients.
16805906 Identification of arthritis-related gene clusters by microarray analysis of two independen 2006 Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1% of the population worldwide. Previously, we showed that human T-cell leukemia virus type I-transgenic mice and interleukin-1 receptor antagonist-knockout mice develop autoimmunity and joint-specific inflammation that resembles human RA. To identify genes involved in the pathogenesis of arthritis, we analyzed the gene expression profiles of these animal models by using high-density oligonucleotide arrays. We found 1,467 genes that were differentially expressed from the normal control mice by greater than threefold in one of these animal models. The gene expression profiles of the two models correlated well. We extracted 554 genes whose expression significantly changed in both models, assuming that pathogenically important genes at the effector phase would change in both models. Then, each of these commonly changed genes was mapped into the whole genome in a scale of the 1-megabase pairs. We found that the transcriptome map of these genes did not distribute evenly on the chromosome but formed clusters. These identified gene clusters include the major histocompatibility complex class I and class II genes, complement genes, and chemokine genes, which are well known to be involved in the pathogenesis of RA at the effector phase. The activation of these gene clusters suggests that antigen presentation and lymphocyte chemotaxis are important for the development of arthritis. Moreover, by searching for such clusters, we could detect genes with marginal expression changes. These gene clusters include schlafen and membrane-spanning four-domains subfamily A genes whose function in arthritis has not yet been determined. Thus, by combining two etiologically different RA models, we succeeded in efficiently extracting genes functioning in the development of arthritis at the effector phase. Furthermore, we demonstrated that identification of gene clusters by transcriptome mapping is a useful way to find potentially pathogenic genes among genes whose expression change is only marginal.