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ID PMID Title PublicationDate abstract
18797411 Tumor necrosis factor alpha-308 and -238 polymorphisms in rheumatoid arthritis. Associatio 2008 Oct BACKGROUND: Rheumatoid arthritis (RA) is characterized by a progressive joint damage mediated mainly by tumor necrosis factor alpha (TNFalpha). We investigated the relationship of TNFalpha-308 and -238 polymorphisms with messenger RNA (mRNA) expression and soluble TNFalpha (sTNFalpha) in 50 RA and 100 healthy subjects (HS). METHODS: Clinical and laboratory assessments were performed. Spanish Health Assessment Questionnaire Disability Index, Spanish version of Arthritis Impact Measurement Scales and Disease Activity Score using 28 joint count indices were applied to RA patients. The TNFalpha-308 and -238 polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism techniques. The mRNA expression of TNFalpha was quantified by real-time polymerase chain reaction. The sTNFalpha levels were measured by enzyme-linked immunosorbent assay. RESULTS: The TNFalpha-308 polymorphism showed an increased frequency of guanine (G)/adenine (A) genotype in RA versus HS (P = 0.03; 95% confidence interval, 1.05-8.08; odds ratio, 2.9) and also the A allele was more frequent in RA patients versus HS (P = 0.04; 95% confidence interval, 1.01-7.29; odds ratio, 2.7). The G/G genotype and also the G allele were more frequent in HS. No significant difference was observed in TNFalpha-238 polymorphism. Rheumatoid arthritis patients showed high TNFalpha mRNA expression (1.33-fold). The G/G genotype was associated with high mRNA and sTNFalpha levels in both TNFalpha polymorphisms. The correlation of sTNFalpha levels with C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, Spanish Health Assessment Questionnaire Disability Index, and Spanish version of Arthritis Impact Measurement Scales, was observed. CONCLUSION: The TNFalpha-308 polymorphism is a susceptibility marker to RA. The G/G genotype is associated with a high mRNA and soluble TNFalpha expression.
18843786 Associations between FCGR3A polymorphisms and susceptibility to rheumatoid arthritis: a me 2008 Nov OBJECTIVE: .To investigate whether the Fcgamma receptor (FCGR) polymorphism confers susceptibility to rheumatoid arthritis (RA). METHODS: We conducted metaanalyses on the associations between FCGR polymorphisms and RA susceptibility as determined using (1) allele contrast, (2) recessive models, (3) dominant models, and (4) contrast of homozygotes, using fixed or random effects models. RESULTS: A total of 10 separate comparisons were considered, which comprised 6 European and 4 Asian population samples. Metaanalysis of FCGR3A polymorphism revealed a significant association between the VV genotype and the risk of developing RA relative to the VF+FF genotype (OR 1.256, 95% CI 1.045-1.510, p = 0.015), with no evidence of between-study heterogeneity (p = 0.167). In subjects of European descent, a stronger association was observed between the VV genotype and RA than for the FF genotype (OR 1.374, 95% CI 1.101-1.714, p = 0.005). In Asians, no such association was found. Metaanalysis of the VV vs FF genotype revealed a significantly increased OR in Europeans (OR 1.399, 95% CI 1.107-1.769, p = 0.005), but not in Asians. No association was found between RA and the FCGR2A and FCGR3B polymorphisms in all subjects and in European and Asian populations, except for the NA22 vs NA11 of FCGR3B in Europeans. CONCLUSION: No relation was found between the FCGR2A polymorphism and susceptibility to RA in Europeans or Asians. The FCGR3A polymorphism was found to be associated with RA in Europeans but not in Asians. The FCGR3B polymorphism was associated with RA susceptibility in Europeans.
17537386 Meta-analysis of HLA-DRB1 polymorphism in Latin American patients with rheumatoid arthriti 2007 Jun OBJECTIVES: To estimate the common effect size of HLA-DRB1 alleles on rheumatoid arthritis (RA) susceptibility across Latin America populations through a meta-analysis combining the results of published data. METHODS: Case-control studies on HLA-DRB1 association with RA in Latin America were searched up to October 2006. Genotype frequencies were extracted according to both shared epitope (SE) and HLA-DR4 positive or negative alleles. The effect summary odds ratio (OR) and 95% confidence intervals was obtained. Heterogeneity and publication bias were assessed. RESULTS: Eight studies containing 684 cases and 1015 controls were included. Under the random effects model, the common OR was 3.28 (1.93, 5.60) (p<0.0001) and 3.54 (2.47, 5.05) (p=4.22 x 10(-12)) for HLA-DR4 and SE, respectively. There was no evidence of publication bias according to Funnel plot and Egger's regression test (p=0,445 for DR4 and p=0,464 for SE meta-analysis). Significant heterogeneity was observed for HLA-DR4 (I2=81.06%, Q=36.96, p=0.000005) but not for the SE meta-analysis. CONCLUSIONS: HLA-DR4 and SE positive HLA-DRB1 alleles (mainly HLA-DRB10404) are associated with RA in Latin Americans. Heterogeneity is expected owing to the diverse degree of admixture between the examined populations. Our findings support the HLA as a major susceptibility locus for RA and validate the SE hypothesis in Latin America.
16641041 Lower urinary tract symptoms in female patients with rheumatoid arthritis. 2006 Mar OBJECTIVE: Patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) are associated with an increased severity of lower urinary tract symptoms (LUTS). Recent surveys also reveal that rheumatoid arthritis (RA) is prevalent in patients with interstitial cystitis (IC). Therefore, we have investigated LUTS in patients with RA. METHODS: A total of 198 female patients with RA, aged 40 years or older, from the rheumatology outpatient clinic completed this prospective study. The American Urological Association Symptom Index (AUASI) score was used to assess the severity of LUTS and the O'Leary-Sant Symptom Index (ICSI) was used to evaluate IC-like urinary symptoms in these patients, which were compared to those of 679 age-matched controls. The possible associations of clinical parameters with LUTS were also explored. RESULTS: The Mean AUASI score and the percentage of individuals reporting severe LUTS (AUASI score > or = 20) or IC-like urinary symptoms (ICSI score > or = 12) showed no significant differences between the RA and control groups. However, in the RA group multivariate regression analyses identified patients with secondary SS (n = 21) to be associated with a significantly higher AUASI score (p = 0.007) and a higher percentage of severe LUTS (p = 0.02); these were also significantly higher than those of the control group (p = 0.02 and p = 0.01, respectively). CONCLUSION: Patients with RA have similar urinary complaints when compared to controls. However, those with secondary SS have a greater severity of LUTS, a finding similar to that observed in patients with primary SS.
17444133 [Report of a rare case of temporomandibular ankylosis as a result of rheumatoid arthritis] 2007 Feb The case and surgical treatment of a patient with rheumatoid arthritis causing bony ankylosis of the temporomandibular joint are presented. The main characteristics of polyarthritis are also surveyed.
18165029 Passive knee kinematics before and after total knee arthroplasty: are we correcting pathol 2008 Jan The change in coronal plane deformity throughout a range of flexion before and after total knee arthroplasty (TKA) has not been reported. Unlike most alignment assessments traditionally reporting coronal plane alignment in a standing position under static conditions, this study reports deformity throughout the flexion arc before and after deformity correction. One hundred fifty-two TKA patients using the anteroposterior axis for femoral component rotation and computer navigation techniques were included in the study. Deformity before TKA ranged from 17.5 degrees varus (deformity apex away from the midline) to 20.5 degrees valgus (deformity apex toward the midline) in full extension. Before TKA, deformity was not constant through an arc of motion and significantly decreased with flexion of 60 degrees and more (P < .01). The deformity after performing a TKA was not different (P = .478) throughout the flexion arc. The data determined that deformity is not constant throughout flexion in osteoarthritic knees preoperatively and that deformity throughout flexion can be corrected with the use of conventional alignment techniques during TKA.
16982148 Impact of low back pain on functional limitations, depressed mood and quality of life in p 2007 Jan Low back pain (LBP) and rheumatoid arthritis (RA) are common orthopedic problems, but there is little information on the importance of LBP in RA patients. The aim of this study was to investigate how LBP affects functional limitations, depressed mood, and quality of life in patients with RA. A complex questionnaire was answered by 281 RA patients, including questions about their RA and their experience of LBP. Functional limitations were assessed using the Hannover Activities of Daily Living questionnaire (ADL), depressed mood using the Center for Epidemiological Studies Depression Scale (CES-D) and health-related quality of life using the Short Form 12 health questionnaire (SF-12). The prevalence of LBP in RA patients was 53.4%. RA patients with LBP displayed a significantly higher degree of disability and depression than RA patients without LBP. There were no differences between the two groups with regard to the duration of RA, the number of operations or medication. LBP is an important factor for the physical and psychological behavior of RA patients. Therefore, the onset of LBP should not be overlooked or underestimated.
17429662 [The mechanism of bone loss in rheumatoid arthritis. Description based on a case report]. 2007 Jul Various factors influencing bone turnover and bone loss in rheumatoid arthritis (RA) are illustrated using the example of a postmenopausal woman with a highly active RA. In particular, the relationships between disease activity, vitamin D metabolism, parathyroid hormone (PTH) levels and calcium metabolism are described. High disease activity is associated with low levels of 25-hydroxycholecalciferol, and especially of 1.25-dihydroxycholecalciferol. Despite vitamin D deficiency, PTH levels were decreased and histomorphometric investigation of the iliac crest biopsy showed severe osteoporosis but no signs of osteomalacia. Suppression of the inflammatory disease activity of RA led to a normalisation of the serum levels of 1.25-dihydroxycholecalciferol and PTH. This was associated with a reduction in the initially increased levels of bone specific alkaline phosphatase to normal values. This case report shows a close relationship between disease activity and bone turnover in RA and indicates that early investigation and therapy of disturbances of bone metabolism in RA are necessary.
19025264 The role of positive and negative interpersonal events on daily fatigue in women with fibr 2008 Nov OBJECTIVE: The current study tested whether daily interpersonal events predicted fatigue from one day to the next among female chronic pain patients. DESIGN: Self-reported fatigue, daily events, pain, sleep quality, depressive symptoms, and functional health across 30 days were assessed in women with rheumatoid arthritis (RA: n = 89), Osteoarthritis (OA: n = 76), and Fibromyalgia syndrome (FM: n = 90). MAIN OUTCOME MEASURES: Self-report fatigue measured on a 0 to 100 scale and fatigue affect from PANAS-X (Watson & Clark, 1994). RESULTS: Multilevel analyses showed that both higher average levels of and daily increases in negative events predicted more fatigue, whereas daily increases in positive events predicted less fatigue. Across all pain conditions, increases in negative events continued to predict higher fatigue on the following day. Moreover, for participants with FM or RA, increases in positive events also predicted increased fatigue the following day. Daily increases in fatigue, in turn, predicted poorer functional health on both the same day and the next day. CONCLUSION: These results indicate that both on average and on a daily basis, interpersonal events influence levels of fatigue beyond common physical and psychological correlates of chronic pain and highlight differences between chronic pain groups.
16755955 [Validation of the Tunisian version of the Health Assessment Questionnaire (HAQ) in rheuma 2006 Mar METHODS: One hundred twenty two rheumatoid arthritis patients were consecutively included in the study. Test-retest reliability was assessed in 61 patients based on the intra-class correlation coefficient. RESULTS: for the 122 patients (104 female and 18 male) the median age was 47 years (18-70). The mean age of the patients who filled in the questionnaire at test and retest times was 45 years (18-70). Test- retest reliability of the HAQ was 0.84. Internal consistency was 0.94. There was a good correlation between the HAQ and the Lee index (r = 0.75, p <10(-4)), the HAQ and the RAQoL (rs = 0.96, p <10(-4)). In a logistic regression model Lee index, RAQoL and age account for the variance of the HAQ. CONCLUSION: The Tunisian version of the HAQ preserves the metrological properties of the original version and can be used for measuring and following functional abilities of Tunisian rheumatoid arthritis patients.
18050378 Relative efficiencies of physician/assessor global estimates and patient questionnaire mea 2008 Feb OBJECTIVE: To estimate relative efficiencies of the 7 rheumatoid arthritis (RA) Core Data Set measures to distinguish adalimumab from control treatments in 4 clinical trials. METHODS: Four adalimumab clinical trials were analyzed for arithmetic and percentage changes for each Core Data Set measure from baseline to endpoint: 3 assessor/physician measures -- swollen joints, tender joints, and global estimate; 1 laboratory test -- C-reactive protein; and 3 patient measures -- physical function, pain, and global estimate. Relative efficiencies of each measure to distinguish adalimumab from control group responses were assessed, with tender joint count as the referent measure. RESULTS: Relative efficiencies were in a similar range for physician/assessor, patient, and laboratory measures, with some variation between trials. Among physician/assessor measures, relative efficiencies for global estimates were greater than for swollen and tender joint counts in 8/8 comparisons. Among patient measures, relative efficiencies for global estimates were greater than for physical function and pain scores in at least 6/8 comparisons. Among all measures, relative efficiencies for patient global estimates were greater than for swollen joint counts in 5/8 comparisons, and for tender joint counts in 8/8 comparisons. CONCLUSION: Patient and physician/assessor measures distinguished adalimumab from control treatment groups in similar ranges. Among all measures, physician/assessor global estimate was most efficient, and tender joint count least efficient, in all 4 trials. This information suggests that while joint counts are the most specific measure to assess RA, their sensitivity to detect treatment effects in patients with RA is generally no greater, and usually less, than other measures.
16896264 Manifestation of rheumatoid arthritis after transsphenoidal surgery in a patient with acro 2006 Oct Acromegalic arthropathy is one of the most frequent manifestations occurring in acromegaly patients. In contrast, rheumatoid arthritis (RA) is a rare clinical complication in acromegaly patients. Here, we report a 70-year-old Japanese woman with acromegaly, who complained of bilateral finger stiffness and polyarthralgia two months after transsphenoidal surgery of a growth hormone (GH)-secreting pituitary adenoma. Postoperative levels of serum GH and insulin-like growth factor-1 (IGF-1) were markedly decreased without any secretory deficiency of other anterior pituitary hormones. Hand X-ray did not show typical RA changes; however, erosive changes in carpal bones were clearly detected by magnetic resonance imaging with gadolinium enhancement. Based on the levels of serological markers in the patient following surgery including C-reactive protein, rheumatoid factor and matrix metalloproteinase-3, anti-rheumatic therapy was subsequently commenced. Regardless of the levels of GH and IGF-1, acromegaly patients frequently complain about joint-related symptoms even after remission. Therefore, careful observation of bone erosive changes and immunological activity in acromegaly patients is required when joint-related symptoms persist.
18354270 [Midterm results of total knee arthroplasty in degenerative knee joint diseases with sever 2008 Jan OBJECTIVES: We evaluated the midterm results of total knee arthroplasty in degenerative knee joint diseases with severe deformity. METHODS: Total knee arthroplasty was performed in 125 knees of 86 patients (75 women, 11 men; mean age 69 years; range 39 to 85 years) with degenerative knee joint diseases accompanied by severe deformity. Almost all the patients had osteoarthritis (100 knees, 80%) or rheumatoid arthritis (22 knees, 17.6%). Thirty-nine patients with bilateral involvement underwent single-stage (n=20) or two-stage (n=19) surgery. During surgery, the posterior cruciate ligament was sacrificed in 108 knees and retained in 17 knees. Pre- and postoperative assessments were made according to the Knee Society clinical scoring system. The mean follow-up was 53 months (range 24 to 96 months). RESULTS: The results were excellent or good in 80.2% of the knees. Nine knees (7.2%) required revision surgery, of which preoperative diagnosis was rheumatoid arthritis in five. The reasons for revision were infection-related problems (n=5), aseptic loosening (n=3), and periprosthetic fracture (n=1). Compared with preoperative values, the mean knee score increased by 60.9 (from 26.2 to 87.1), and the mean functional score increased by 42.6 (from 33.2 to 75.8) (p<0.05), with a mean range of knee joint motion of 93.2 degrees . The mean preoperative and postoperative alignments were 17.8 degrees of varus and 4.1 degrees of valgus (range 0 degrees to 6 degrees ), respectively. The number of knees with a flexion contracture decreased from 68 (mean 28.8 degrees ) to 8 (mean 8.4 degrees ), all of which had a flexion contracture angle below 10 degrees . CONCLUSION: Total knee arthroplasty performed in degenerative knee joint diseases with severe deformity significantly improves patients' complaints and functional results.
18590108 [Painless myocardial ischemia in patients with rheumatoid arthritis]. 2008 AIM: To ascertain prevalence and prognostic implication of painless myocardial ischemia (PMI) in patients with rheumatoid arthritis (RA) in respect to stage, severity of inflammation and characteristics of the lipid profile. MATERIAL AND METHODS: A 24-h Holter ECG monitoring, tests for total cholesterol, triglycerides and lipid spectrum were made in 94 patients with a documented rheumatoid arthritis (RA) aged 36-68 years (mean age 54.8 +/- 8.0 years, 13 males and 81 females) admitted to Toliatti municipal hospital N 4. The control group consisted of 20 patients with a history of myocardial infarction. Forty RA patients were followed up for mean 1.1 year after basic therapy. RESULTS: Holter ECG monitoring detected ischemic depression of ST segment in 46 (48.9%) RA patients and 9 (45%) patients with coronary heart disease. RA patients with PMI had changes in the lipid profile in the direction of elevation of atherogenic components and C-reactive protein characterizing severity of inflammation. Basic treatment of RA eliminated PMI symptoms in some patients. This correlated with attenuation of inflammation. Some RA patients had first symptoms of PMI, on the average, on follow-up year 1.1 and higher plasmic atherogenicity. CONCLUSION: About 50% RA patients free of clinical symptoms of coronary heart disease had PMI caused by both coronarogenic (atherosclerotic) factors and non-coronarogenic (immunocomplex inflammation) mechanisms.
16356192 Adalimumab clinical efficacy is associated with rheumatoid factor and anti-cyclic citrulli 2006 Studies on autoantibody production in patients treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors reported contradictory results. We investigated in a prospective study the efficacy of a treatment with human monoclonal anti-TNF-alpha antibody (adalimumab) in patients with rheumatoid arthritis (RA) and we evaluated the relationship between treatment efficacy and the incidence and titers of disease-associated and non-organ-specific autoantibodies. Fifty-seven patients with RA not responsive to methotrexate and treated with adalimumab were enrolled. Antinuclear, anti-double-stranded(ds)DNA, anti-extractable nuclear antigens, anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI) autoantibodies, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies were investigated at baseline and after 6 and 12 months of follow-up. Comparable parameters were evaluated in a further 55 patients treated with methotrexate only. Treatment with adalimumab induced a significant decrease in RF and anti-CCP serum levels, and the decrease in antibody titers correlated with the clinical response to the therapy. A significant induction of antinuclear autoantibodies (ANA) and IgG/IgM anti-dsDNA autoantibodies were also found in 28% and 14.6% patients, respectively, whereas aCL and anti-beta2GPI autoantibodies were not detected in significant quantities. No association between ANA, anti-dsDNA, aCL and anti-beta2GPI autoantibodies and clinical manifestations was found. Clinical efficacy of adalimumab is associated with the decrease in RF and anti-CCP serum levels that was detected after 24 weeks and remained stable until the 48th week of treatment. Antinuclear and anti-dsDNA autoantibodies, but not anti-phospholipid autoantibodies, can be induced by adalimumab but to a lower extent than in studies with other anti-TNF blocking agents.
17321817 Effect of motorized scooters on physical performance and mobility: a randomized clinical t 2007 Mar OBJECTIVE: To investigate the effects of providing a motorized scooter on physical performance and mobility. DESIGN: Randomized clinical trial comparing scooter users with usual care. SETTING: One academic and 1 Veterans Affairs medical center. PARTICIPANTS: Ambulatory, community-dwelling outpatients with rheumatoid arthritis or osteoarthritis of the knee. INTERVENTION: Provision of a motorized scooter for 3 months. MAIN OUTCOME MEASURES: Six-minute walk distance (6MWD) and mobility methods in diverse locations at baseline, 1 month, and 3 months, and accidents while using the scooter. RESULTS: The majority of scooter subjects (n=16/22 [72.7%]) used the scooter 4 or more days per week. The difference+/-standard deviation between the 2 groups in change in 6MWD over the study period was not statistically significant (scooter users, 16.9+/-73.0 m [55.5+/-239.6 ft]; usual care, 17.2+/-72.5 m [56.5+/-238.0 ft], P=.55). Four (18.1%) scooter users reported 9 accidents. Over the study period, the proportion of persons reporting use of a scooter (provided by the study or otherwise available) increased in the scooter-users group (eg, food stores, 16.7% to 52.6%; doctor's office, 0% to 35.7%) but not the usual-care group (food stores, 9.1% to 9.5%; doctor's office, 0% to 0%). CONCLUSIONS: Motorized scooters provided to ambulatory persons with arthritis were used intermittently. The greatest short-term risk from scooter usage appeared to be minor collisions.
18484150 BDNF in RA: downregulated in plasma following anti-TNF treatment but no correlation with i 2008 Oct The involvement of brain-derived neurotrophic factor (BDNF) in rheumatoid arthritis (RA) is largely unknown. The distribution of BDNF and its associated receptors, TrkB and p75, in the synovial tissue of patients with RA was examined and contrasted with that in patients with osteoarthritis (OA). Additionally, levels of BDNF in both synovial tissue and synovial fluid were measured. Furthermore, the effects of anti-tumour necrosis factor (anti-TNF; infliximab) treatment on BDNF levels in the plasma of RA patients were analysed. Cells in the synovium showed immunoreactivity for BDNF and BDNF-, p75- and TrkB-receptor immunoreactions were seen in nerve fibres of nerve fascicles and in association with sensory corpuscles. The levels of BDNF in synovial tissue were not correlated with the number of inflammatory cells observed microscopically or with levels of TNFalpha. Nor did the BDNF levels in synovial fluid correlate with erythrocyte sedimentation rate (ESR) or white blood cell counts. Anti-TNF treatment lead to a decrease in plasma levels of BDNF 14 weeks after the initiation of anti-TNF therapy, i.e., 8 weeks after the last infusion. Higher levels of BDNF were observed in RA patients at baseline compared with those for healthy individuals. However, the levels of BDNF in plasma of patients treated with anti-TNF did not correlate with the changes in ESR or a disease activity score. The clinical significance of this study is that anti-TNF treatment influences plasma levels of BDNF although there was no evidence that BDNF levels correlate with inflammatory parameters in either infliximab-treated or non-infliximab-treated patients with RA. Instead it is likely that sources other than inflammatory cells, including nerve structures, are important sources of BDNF and that the effects of anti-TNF treatment on BDNF levels may be related to effects on circulating and various local cells and/or BDNF-containing neurons.
18381798 Serum antibodies against intact human collagen IX are elevated at onset of rheumatoid arth 2008 May OBJECTIVE: To measure the presence of autoantibodies binding to intact human recombinant collagen IX and assess their usefulness as a diagnostic marker and an indicator of disease activity in rheumatoid arthritis (RA). METHODS: Recombinant human full-length collagen IX (rCIX) was produced in a baculovirus expression system and purified for use in ELISA developed to detect antibodies to native and denatured collagen IX. Fifty-three patients with recent-onset rheumatoid factor-seropositive RA were analyzed for the presence of rCIX antibodies of the IgG type at the time of initial diagnosis and after 3, 6, 12, and 24 months of followup. The RA sera were accompanied by 30 controls. Associations were determined between patients' antibody titers, development of erosions in the hands and feet, and various clinical and laboratory markers. RESULTS: Serum antibody levels among patients with RA at time of diagnosis were 1.78 times higher against native rCIX (p < 0.001) and 1.71 times higher against denatured rCIX (p < 0.001) than in the controls, and they remained high during the followup. No correlation was seen between antibody levels and clinical and laboratory findings. CONCLUSION: Our data show that patients with recent-onset RA have significantly elevated levels of autoantibodies to human rCIX. These autoantibodies were observed already at the early stages of the disease, which may reflect their diagnostic potential in RA.
18035327 RAG-mediated secondary rearrangements of B-cell antigen receptors in rheumatoid synovial t 2007 Dec Rheumatoid arthritis (RA) induces major changes in synovial tissue (ST) and cartilage and bone destruction. Still, its pathogenesis is poorly understood. Accumulating evidence points to an important role for B lymphocytes. Rheumatoid-ST is characterized by activation of the synoviocytes and infiltrated by various inflammatory cells such as B and T lymphocytes. The infiltrate is diffuse or organized as germinal centers (GCs). These accommodate the immune response and favor self-tolerance breakdown. Receptor revision in B cells results from re-expression of the recombination activating genes (RAGs) which reinitiate immunoglobulin gene recombination, and modify the B-cell antigen receptor accordingly. In rheumatoid ST, secondary VDJ rearrangements occur and RAG proteins are detected. The mechanism that triggers and controls this revision remains elusive. We favor the hypothesis that such an uncontrolled process leads to autoimmunity.
18625278 Association of a TRAF1 and a STAT4 gene polymorphism with increased risk for rheumatoid ar 2008 Sep Rheumatoid arthritis (RA) is a multifactorial disease that is increasing in incidence worldwide. It is associated with a complex mode of inheritance, with many genes being involved in the development and progression of the disease. Genome-wide association studies in different populations have recently revealed a significant association between a TRAF1/C5 and a STAT4 polymorphism and the development of RA. In the present study we performed a case-control study in the population of the island of Crete, Greece, aiming to replicate the former findings in a genetically homogeneous cohort of patients. We found that mutated allele A or genotypes A/A and G/A of the TRAF1/C5 rs10818488 SNP were more common in individuals with RA than in control individuals (odds ratio [OR]=1.7, 95% confidence interval [CI]=1.35-2.15, and OR=2.22, 95% CI=1.61-3.05, respectively). Similarly, mutated allele T or genotypes T/T and G/T of the STAT4 rs7574865 SNP were also associated with susceptibility to RA (OR=1.9, 95% CI=1.46-2.50, and OR=2.37, 95% CI 1.73-2.25, respectively). Thus, we conclude that mutant alleles or genotypes of both polymorphisms examined are associated with the development of RA in our population.