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ID PMID Title PublicationDate abstract
9811891 NF-kappaB activation provides the potential link between inflammation and hyperplasia in t 1998 Nov 10 The transcription factor NF-kappaB is a pivotal regulator of inflammatory responses. While the activation of NF-kappaB in the arthritic joint has been associated with rheumatoid arthritis (RA), its significance is poorly understood. Here, we examine the role of NF-kappaB in animal models of RA. We demonstrate that in vitro, NF-kappaB controlled expression of numerous inflammatory molecules in synoviocytes and protected cells against tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) cytotoxicity. Similar to that observed in human RA, NF-kappaB was found to be activated in the synovium of rats with streptococcal cell wall (SCW)-induced arthritis. In vivo suppression of NF-kappaB by either proteasomal inhibitors or intraarticular adenoviral gene transfer of super-repressor IkappaBalpha profoundly enhanced apoptosis in the synovium of rats with SCW- and pristane-induced arthritis. This indicated that the activation of NF-kappaB protected the cells in the synovium against apoptosis and thus provided the potential link between inflammation and hyperplasia. Intraarticular administration of NF-kB decoys prevented the recurrence of SCW arthritis in treated joints. Unexpectedly, the severity of arthritis also was inhibited significantly in the contralateral, untreated joints, indicating beneficial systemic effects of local suppression of NF-kappaB. These results establish a mechanism regulating apoptosis in the arthritic joint and indicate the feasibility of therapeutic approaches to RA based on the specific suppression of NF-kappaB.
10804750 [Can Helicobacter pylori infection be a risk factor for the severity of rheumatoid arthrit 2000 Apr AIM: In this study we assessed the effect of Helicobacter pylori eradication in patients with established rheumatoid arthritis (RA) in order to show a possible pathogenetic role of the infection in this disease. METHODS: We recruited 31 patients with variable RA activity. Of them, 15 were Hp-positive (12 F and 3 M, mean age 55 +/- 10.6 years) and 16 Hp-negative (13 F and 3 M, mean age 54.2 +/- 9.1 years) on the basis of the concomitant positive or negative findings of both CLO-test and histology performed on both antral and corpus biopsies. The infected group was treated and the bacterium was considered eradicated when both tests were negative a month after therapy. We have evaluated the disease activity at baseline and during a total follow-up period of 16 months with check-points every 4-months and compared clinical and laboratory findings between the Hp-negative and the eradicated groups. Both groups were being treated with NSAIDs and prednisolone (< or = 7.5 mg/die) or its equivalents. RESULTS: Hp-eradicated RA patients showed a progressive improvement overtime (p = 0.0009) of all clinical indices compared with baseline, while Hp-negative RA patients did not. At the 16-month checkpoint, the eradicated RA patients differed significantly (p < 0.006) from patients without Hp infection by all indices, except grip strength of the hands. Also all laboratory data improved significantly from baseline to the 16 month checkpoint (p < 0.03) within the Hp-eradicated group and between the two groups of eradicated and Hp-negative RA patients (p < 0.0007) except for Hb, aCL IgM and gamma-globulins. CONCLUSIONS: Our data suggest that Hp infection is implicated in the pathogenesis of RA. On the basis of our data, the eradication of Hp should be recommended in infected RA patients.
11791636 Serum YKL-40 levels in rheumatoid arthritis: correlations between clinical and laborarory 2001 Nov OBJECTIVE: To clarify the significance of YKL-40, also called human cartilage glycoprotein-39, in the serum of patients with RA, we studied serum YKL-40 in relation to clinical and laboratory parameters. METHODS: Seventy-two patients (16 men and 56 women) with RA and 40 age-matched healthy persons (14 men, 26 women) were included in this study. Serum levels of YKL-40, insulin-like growth factor-I (IGF-I) and interleukin-6 (IL-6) were measured by ELISA. Radiological changes reflecting joint destruction and the joint score for pain or swelling were assessed by taking into account the joint surface area. Serum CRP levels and the functional disability of patients were also determined. RESULTS: YKL-40 levels in the serum of patients with RA were significantly higher than those of controls (p < 0.0001), and showed positive correlations with serum levels of IL-6 (r = 0.301, p = 0.011) and CRP (r = 0.326, p = 0.006), but negative correlations with serum levels of IGF-I (r = -0.340, p = 0.004). The radiological score, but not joint pain, also correlated with YKL-40 levels (r = 0.364, p = 0.002). As the functional disability of patients became severe, the serum YKL levels increased. CONCLUSION: Serum YKL-40 levels partially reflect the degree of inflammation and also reflect the joint destruction in patients with RA.
11307134 Change in pain and function while waiting for major joint arthroplasty. 2001 Apr The objective of this study was to examine the change in pain and physical function that occurs while waiting for major arthroplasty. Data were collected prospectively from a cohort of 313 patients who were waiting > 1 month for total hip arthroplasty or total knee arthroplasty. The WOMAC and the SF-36 health status instruments were administered at the time the patient was placed on the waiting list and again just before surgery. Minimal amounts of change in pain and physical and psychosocial function occurred for hip and knee arthroplasty patients while they waited. Overall, waiting time did not appear to have a negative impact on the amount of pain and dysfunction experienced.
10627716 Late results of total shoulder replacement in patients with rheumatoid arthritis. 1999 Sep Rheumatoid arthritis of the shoulder is a progressive and destructive joint disease, and similar to arthritis in other joints, progression of the disease is unpredictable and may stop at any stage of involvement. Between 1983 and 1996, more than 500 shoulder prostheses were implanted in patients at the authors' institution. Total shoulder replacement yields satisfactory short and long term results even in patients with severely destructed joints. Pain relief is reliable and significant as reported in short and long term studies. In most patients the functional result is good or acceptable. Although range of motion is only slightly increased, a satisfactory overall range of motion is achieved by most patients because of the unaffected scapulothoracic motion. However, deteriorating results, emphasizing the complexity of shoulder arthroplasty, were seen with increasing observation time in patients with rheumatoid arthritis. Proximal migration of the humeral prosthesis attributable to rotator cuff failure, with secondary eccentric glenoid loading and progressive loosening, is latent in patients with chronic progressive rheumatoid disease and was by far the most common complication (42%) in the present series.
11312381 Screening for extensor tendon rupture in rheumatoid arthritis. 2001 Apr OBJECTIVE: Surgery can prevent extensor tendon rupture in the rheumatoid wrist but it is difficult to identify patients at risk. Extensor digiti minimi (EDM) usually ruptures first, but rupture may pass unnoticed because extensor digitorum communis (EDC) extends all four fingers simultaneously. We assessed the value of screening for EDM rupture by examining for absent independent extension of the little finger in a hospital rheumatoid arthritis population. METHODS: The EDM test was performed in 550 previously unoperated wrists. Disease activity, joint damage, wrist swelling, tenderness and crepitus were recorded. RESULTS: Unsuspected EDM loss was found in nine of the 550 wrists (1.6%); dorsal synovitis was absent or minimal in eight and ulnar tenderness was absent in six. EDM loss was not associated with activity, severity or duration of disease. CONCLUSIONS: The EDM test is simple and cheap. It may identify patients at risk and permit prophylactic surgery before hand function is lost.
10982689 Activity of rheumatoid arthritis and urinary pyridinoline and deoxypyridinoline. 2000 The aims of this study were to examine levels of the crosslinking components of collagen, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) which are bone resorption markers, in patients with rheumatoid arthritis (RA), and to determine their association with disease activity and bone mineral density (BMD). These bone resorption markers were measured in 35 postmenopausal women with RA, 30 age-matched female patients with osteoarthritis of the knee (controls), and 47 patients with bone fracture. The mean BMD in the RA patients was lower than that in the control group, and the Z-score (number of standard deviations above and below the normal mean after comparison with age and sex matched normal control values) was significantly lower. Mean levels of Pyr and D-Pyr were significantly higher in the RA patients than in the control group, and the Pyr/D-Pyr ratio was also higher in the RA patients than in the other groups. Regarding the relationship between the bone resorption markers and RA activity, Pyr increased as the Lansbury's joint score (number of swollen joints corrected for joint size according Lansbury) rose, showing a normal correlation; D-Pyr also showed a normal correlation. Pyr and D-Pyr were high in patients with a high erythrocyte sedimentation rate, showing a normal correlation. Only Pyr increased with increases in C-reactive protein (CRP), showing a normal correlation. These findings suggested that a high value for Pyr (which includes a large amount of collagen type II) indicated that RA activity was affected more by synovitis, rather than by systemic osteoporosis.
9613337 Improved functional outcome in patients with early rheumatoid arthritis treated with intra 1998 Feb OBJECTIVE: To determine whether there is a relation between disease duration and functional outcome in patients with rheumatoid arthritis (RA) treated with intramuscular sodium aurothiomolate (gold) for five years. METHODS: 440 patients with RA were enrolled in a prospective trial of gold treatment. Initial demographic details were recorded. Disease activity was assessed at yearly intervals using a combination of clinical (pain score, Ritchie articular index, duration of morning stiffness) and laboratory (erythrocyte sedimentation rate, C reactive protein) parameters. Change in functional status was assessed using the health status questionnaire (HAQ). Patients were stratified according to disease duration at outset (group 1 = 0-2 years n = 106, group 2 = > 2-5 years n = 93, and group 3 = > 5 years n = 235). RESULTS: There were no significant differences between the groups at outset. A total of 160 patients completed five years of treatment (group 1 n = 44 (42%), group 2 n = 37 (40%), and group 3 n = 79 (34%)). Patients in group 1 had a significantly lower HAQ from year 1 to year 5 with a mean improvement of 30% at the end of the study (p < 0.001). Neither group 2 nor group 3 had a significant change in their HAQ at study end. There were significant improvements in all other variables (p < 0.05) in each group apart from pain in group 2. CONCLUSION: Patients with early RA have a larger reversible component to their HAQ. Only patients with disease duration of up to two years have a longlasting improvement in their functional ability after starting intramuscular gold treatment.
9747789 Mechanical properties of wrist extensor tendons are altered by the presence of rheumatoid 1998 Jul The in vitro mechanical properties of 14 wrist extensor tendons salvaged at surgery from patients with inflammatory (rheumatoid) arthritis and noninflammatory arthrosis were measured in uniaxial tension and compared. The rheumatoid tendons had higher extensibility at low stresses, lower stiffness in the linear portion of the stress-strain curve, greater rates of stress relaxation, and lower ultimate strengths than did the nonrheumatoid tendons. Differences in tangent modulus, stress remaining at 100 seconds, and ultimate tensile strength were significant at the 95% confidence level. In vivo, mechanically impaired tendons may play an important role in destabilization of the wrist in patients with rheumatoid arthritis.
10547275 Flow cytometrical determination of interleukin 1beta, interleukin 6 and tumour necrosis fa 1999 Nov Experimental data suggest that pro-inflammatory cytokines such as interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) are important in the pathogenesis of osteoporosis in rheumatoid arthritis. Therefore we compared the production of these cytokines by monocytes in 10 rheumatoid arthritis patients and 10 controls. Cytokine levels in rheumatoid arthritis patients were related to disease activity parameters, bone mineral density (BMD) corrected for age and sex (Z scores) and osteocalcin as a laboratory parameter of bone remodelling. Cytokines were determined by a flow cytometrical technique. There was a tendency for higher IL-1beta levels in patients compared with controls. A positive correlation between erythrocyte sedimentation rate and spontaneous production of monocytic cytokines was found. Z scores of the lumbar spine showed a negative correlation with spontaneous production of IL-1beta and IL-6. Plasma osteocalcin levels were positively correlated with spontaneous production of IL-1beta, IL-6 and TNF-alpha. In conclusion, the correlation of the levels of these cytokines with parameters of bone metabolism and osteoporosis suggest that especially IL-1beta and IL-6 are associated with more pronounced osteoporosis in active rheumatoid arthritis.
11085811 Do B cells influence disease progression in chronic synovitis? Lessons from primary hypoga 2000 Nov We describe a 62-yr-old male patient with primary hypogammaglobulinaemia (PH) who fulfilled the 1987 American Rheumatism Association/American College of Rheumatology revised diagnostic criteria for rheumatoid arthritis (RA) but, despite persistent symmetrical synovitis, did not develop erosions. Virology studies and blood and synovial fluid (SF) cultures were consistently negative; a search for crystals in the SF was unrevealing. Peripheral blood (PB) B cells were absent, whilst the PB CD3(+) cell count was normal. The ratio of naive (CD45RA(+)) to memory (CD45R0(+)) cells was also normal (1:1) but the CD4:CD8 ratio was reversed. To our knowledge, this is the first report which combines the immunophenotypic analysis of the PB with that of the SF and synovial membrane (SM). This confirmed the absence of B cells and the reversed CD4:CD8 ratio. However, as in other chronic arthropathies, the SF and SM cellular infiltrate consisted almost exclusively of memory T cells, consistent with the preferential localization of this subset to inflamed tissues. This case indicates that synovitis can proceed persistently in the absence of B cells and that the migratory mechanisms of T cells are not altered. However, the case suggests that the absence of B cells and negativity for rheumatoid factor, combined with an increased presence of CD8(+) (suppresser/cytotoxic) T cells in the joint, might contribute to the non-erosive nature of the synovitis.
10328581 T-cell responses in rheumatoid arthritis: systemic abnormalities-local disease. 1999 May One manifestation of rheumatoid arthritis (RA) is a destructive inflammation of the joint, but many other organs can be targeted by this disease, classifying it as a truly systemic disorder. Accordingly, pathogenic models have to account for the multiorgan character of RA. This article proposes that the primary abnormalities in RA lie in the assembly of the T-cell pool and in the maintenance of T-cell homeostasis. Evidence has accumulated that the repertoire of CD4 T cells in RA patients is distinct and includes a high frequency of disease-relevant T cells. Emergence of T cells with self-aggressive potential could indicate a failure of negative selection in the thymus. Also, the turnover of mature T cells in the periphery is altered in RA patients with a sharp contraction in diversity. Loss of diversity results from the replacement of rare T-cell specificities by multiplying T-cell clones. Large clonal T-cell populations in RA patients acquire a distinct phenotype (CD4+CD28null) and functional profile (overproduction of interferon-gamma, cytotoxicity), giving them the ability to function as proinflammatory cells. Optimal conditions for T-cell stimulation are encountered in the synovium, where ectopic lymphoid tissue with germinal centers is formed. Considering the systemic nature of RA, therapeutic strategies suppressing synovial inflammation while ignoring systemic abnormalities could lack the potential of a curative intervention.
11196538 Association between insulin-like growth factor status and physical activity levels in rheu 2001 Jan OBJECTIVE: To determine if the altered insulin-like growth factor (IGF) status in rheumatoid arthritis (RA) is due to inflammation, altered body composition, or lack of exercise. METHODS: Subjects included 73 patients with RA, 54 patients with other rheumatic diseases, both inflammatory and noninflammatory, and 28 healthy, physically active controls. Serum levels of IGF-I, IGF-II, and IGF binding protein-3 (IGFBP-3) were measured by radioimmunoassay. Body composition was estimated by bioelectrical impedance analysis, and habitual exercise level approximated by questionnaire. Statistical analysis was performed by 2 and 3 way ANOVA and moderated hierarchical regression. RESULTS: Serum IGF-I (p < 0.001), IGFBP-3 (p < 0.001), and the BP-3:total IGF molar ratio (p < 0.001) were depressed in both patient groups relative to controls. In contrast, IGF-II levels were depressed only in patients with RA (p < 0.01). Differences in the IGF proteins between patients and controls could not be attributed to inflammation. Habitual exercise level, but not body composition, was shown to be a significant predictor for IGF-I, IGFBP-3, and BP-3:total IGF molar ratio (p < 0.001). CONCLUSION: Our results indicate that the reduction in circulating IGF proteins observed in our patients is more related to their sedentary lifestyle than to the inflammatory process. This conclusion is in agreement with reports that show that highly active individuals typically exhibit higher levels of systemic IGF proteins than age matched sedentary controls.
9833237 [Prevalence and depression degree in patients with rheumatoid arthritis]. 1998 Oct 3 BACKGROUND: Study goals were: a) to know the existence and depressive level among a series of rheumatoid arthritis (RA) patients; b) to assess differences in depression levels of individuals with and without RA, and c) to identify the association of depression level with socioepidemiological, clinical, and prognostic characteristics in these patients. MATERIAL AND METHODS: Cross-sectional study that undertakes a 3 years period (July 1992-March 1995) and includes 221 patients diagnosed of RA according to the 1988 criteria of the American College of Rheumatology (ACR). Association of depression levels, assessed with the Self-Rating Depression Scale of Zung-Conde, with each one of the variables was evaluated using chi 2 tests (p < 0.05). A multivariate analysis type Automatic Interaction Detection (AID), based on the statistic r2, was applied to determine patient's profile with RA and depression. RESULTS: Depressive level was identified in 33.48% of patients. Odds ratio (OR) between "not depressive" and "depressive" levels was from 20.35 with 95% CI: 8.87-47.88 (p < 0.00001). Association was found with the variables sex (p < 0.0001), profession (p = 0.02), weight and height (p < 0.0001 in both variables), Ritchie index (p < 0.004), number of painful joints (p = 0.002), morning stiffness (p = 0.049) and secondary effects of the treatment (p = 0.034). Sex was the variable that most influenced in depressive level (p < 0.00001). In females group, the factor mainly related with depression was the number of painful joints (p < 0.0002) while in males, it was the self-rating pain valuation with a Likert scale (p < 0.0001). CONCLUSIONS: RA could causes depression in the patients. The factor with highest influence in the depression of these patients was the sex. The most influential factor in the females was the number of painful joints, while in the males was the self-rating of pain.
9247577 Complex CD44 splicing combinations in synovial fibroblasts from arthritic joints. 1997 Jul CD44 is a broadly expressed cell surface glycoprotein which is the major cell surface receptor for the glycosaminoglycan, hyaluronan. In humans, alternative splicing of up to 9 variant exons (v2-v10) into CD44 mRNA, together with post-translational modification via glycosylation and chondroitin sulfate attachment has the potential of generating a large number of CD44 isoforms. Insertion of these various exons has the potential to change the functional capacities of the molecule and has implications in disease. We have analyzed CD44 splice variant expression in cultured VCAM-1-positive synovial fibroblasts isolated from patients with osteo- or rheumatoid arthritis and from normal synovium. Rheumatoid and osteoarthritic tissue express CD44 splice variants at the cell surface level. At the mRNA level exons v3, v6, v7, v8, v9 and v10 were detected in different splicing combinations. Rheumatoid tissue showed high expression, osteoarthritic tissues showed great variation. In contrast, non-inflamed tissue showed no splicing events. Our results indicate that the nature of CD44 splice variant expression may be linked to the inflammatory state of the synovial joint.
10919618 Clinical comparison of two total ankle replacements. 2000 Jul We compared the outcome of the cemented Thompson Parkridge Richards (TPR) ankle prosthesis with that of the cementless Scandinavian Total Ankle Replacement (STAR) ankle prosthesis in a demographically similar group of patients. These were 14 consecutive arthroplasties in 12 rheumatoid arthritis patients, all operated on by the same surgeon. The status of all patients, five years or more after surgery, is known. The mean follow-up periods for the TPR group and the STAR group are 7.2 and 5.4 years respectively. Four of the six TPR tibial components became radiographically loose within two years of surgery. Two of these have been converted to fusions. The STAR prostheses remain satisfactory both clinically and radiographically at five years.
9184919 Detection of Epstein-Barr virus-encoded small RNA 1 and latent membrane protein 1 in synov 1997 May Several investigators have demonstrated an association between Epstein-Barr virus (EBV) and the pathogenesis of rheumatoid arthritis (RA). However, there is no direct evidence that this virus exists in the synovial cells of patients with RA. We attempted to detect EBV in synovial cells from RA patients. Specimens of synovial tissues from 34 patients with RA and from 20 patients with osteoarthritis (OA), and from one patient with psoriatic arthritis as controls, were examined for evidence of the EBV by in situ hybridization. The specimens were also tested by immunoperoxidase staining for expression of the CD21 molecule (EBV receptor), EBV nuclear antigen (EBNA)-2 and latent membrane protein (LMP)-1. EBV-encoded small RNA-1 (EBER) was demonstrated in synovial lining cells from eight (23.5%) out of 34 RA patients but in none of 20 OA patients (P < 0.05) nor in the one psoriatic arthritis patient. Interestingly, EBER localized in synovial lining cells that were located at the apex of villus proliferating lesions. Furthermore, LMP-1 was also detected in synovial lining cells at the top of villus lesions. Nevertheless, CD19 and CD21 molecules, and EBNA-2 were not demonstrated in such lesions. The incidence of EBV-positive in synovial lining cells with severely infiltrated lymphocytes tended to be higher than that in moderately infiltrated ones. This is the first evidence that EBV exists in chronically inflamed synovial lining cells of human joints in RA.
10698334 FHL-1/reconectin and factor H: two human complement regulators which are encoded by the sa 1999 Sep FHL-1/reconectin and factor H are two human complement regulators which are encoded by a single gene. FHL-1/reconectin contains the first 7 of 20 SCR protein domains of factor H and has four unique residues attached to its C-terminal end. The overlapping region of 445 amino acids explains the related complement regulatory functions of the two proteins. However, unique biological functions have also been reported for FHL-1/reconectin, such as cell adhesion and binding to microbial surfaces. Both proteins are synthesised and secreted by the liver. Extrahepatic synthesis occurs in a wide variety of cells, e.g. in monocytes, fibroblasts or neuronal cells. Unexpectedly, FHL-1/reconectin and factor H exhibit distinct expression patterns. This is also observed in disease situations such as in rheumatoid arthritis or malignancies. In rheumatoid arthritis a potentially protective role is suggested by the local synthesis of both FHL-1/reconectin and factor H in synovial fibroblasts and their induction by the anti-inflammatory agent dexamethasone and the cytokine IFN-gamma, but not by TNF-alpha. FHL-1/reconectin is overexpressed in certain tumor cells such as glioblastoma, conferring an exceptional resistance to such cells against complement mediated lysis. Although FHL-1/reconectin and factor H are encoded by a single gene, regulated by the same gene promoter and initiate transcription at the same start site, their transcripts are differently regulated. The putative control levels, which are responsible for this complex regulation, include transcript elongation, RNA processing, alternative splicing and differential poly(A) site selection.
10402069 Detection of mycoplasmal infections in blood of patients with rheumatoid arthritis. 1999 Jun OBJECTIVE: Mycoplasmal infections are associated with several acute and chronic illnesses. Some mycoplasmas can enter a variety of tissues and cells, and cause system-wide or systemic signs and symptoms. METHODS: Patients (14 female, 14 male) diagnosed with rheumatoid arthritis (RA) were investigated for mycoplasmal infections in their blood leucocytes using a forensic polymerase chain reaction (PCR) procedure. Amplification was performed with genus- and species-specific primers, and a specific radiolabelled internal probe was used for Southern hybridization with the PCR product. Patients were investigated for the presence of Mycoplasma spp., and positive cases were further tested for infections with the following species: M. fermentans, M. hominis, M. pneumoniae and M. penetrans. RESULTS: The Mycoplasma spp. sequence, which is not entirely specific for mycoplasmas, was amplified from the peripheral blood of 15/28 patients (53.6%) and specific PCR products could not be detected in 13 patients (46.4%). Significant differences (P < 0.001) were found between patients and positive healthy controls in the genus test (3/32) and in the specific tests (0/32). Moreover, the incidence of mycoplasmal infections was similar in female and male patients. Using species-specific primers, we were able to detect infections with M. fermentans (8/28), M. pneumoniae (5/28), M. hominis (6/28) and M. penetrans (1/28) in RA patients. In 36% of the patients, we observed more than one Mycoplasma species in the blood leucocytes. All multiple infections occurred as combinations of M. fermentans with other species. CONCLUSIONS: The results suggest that a high percentage of RA patients have systemic mycoplasmal infections. Systemic mycoplasmal infections may be an important cofactor in the pathogenesis of RA, and their role needs to be explored further.
9098939 Polymorphism of TAP1 and TAP2 in Japanese patients with rheumatoid arthritis. 1997 Mar Contribution of polymorphism of transporter associated with antigen processing 1 and 2 (TAP1 and 2) alleles to pathogenesis of Japanese rheumatoid arthritis (RA) was studied in 92 RA patients by PCR-RFLP. The allele frequency of TAP2A was slightly low (38.0%) and the frequencies of TAP2B and TAP2C were slightly high (39.7% and 17.9%) in RA, but these differences were not significant. These increases and decrease were due to the positive or negative associations with HLA-DRB1*0405. It was very likely that slight differences in TAP2A, TAP2B and TA2C in RA were secondary phenomenon reflecting an increase in HLA-DRB1*0405. The prevalence of TAP2E allele was low (3.3%, P < 0.01, Pc = not significant) and not correlated with HLA-DRB1*0405.