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ID PMID Title PublicationDate abstract
15693111 The role of B cells in the pathogenesis of rheumatoid arthritis. 2005 Feb The classical paradigm for rheumatoid arthritis (RA) pathogenesis holds that CD4+ T cells mediate joint damage both directly and by driving non-T effector cells to release inflammatory cytokines. By contrast, the new paradigm that is developing centers on an interaction of CD4+ T cells with B cells. Evidence reviewed in this article shows that autoreactive B cells can be driven by the T cells to produce IgG autoantibodies that may be directly involved in joint damage, and B cells are known to be critical in activating CD4+ T cells. As the B cell appears to play an important role in the RA process, it is appropriate to consider how B cell-mediated effects might be reduced or prevented in patients with this disease. As the targeted depletion of B cells with a monoclonal antibody such as rituximab appears to be clinically effective in RA patients, this approach shows great therapeutic potential.
16606645 Polymorphism at position +896 of the toll-like receptor 4 gene interferes with rapid respo 2006 Sep The aim of this study was to determine whether the +896 A-->G substitution of the Toll-like receptor 4 (TLR4) gene, causing the Asp299-->Gly change in the extracellular domain of TLR4, influences treatment response in recent-onset rheumatoid arthritis. 169 patients with rheumatoid arthritis were genotyped from the Finnish Rheumatoid Arthritis Combination Therapy trial, in which they were treated either with only one disease-modifying antirheumatic drug (DMARD) with or without prednisolone (single group), or with three DMARDs and prednisolone (combination group). Patients homozygotic for the wild-type +896A allele were compared with those having the polymorphic G allele in terms of early clinical response (at 6 months) by the 28-joint Disease Activity Score (DAS28). 1 of 20 (5%; (95% (confidence interval (CI) 1 to 5)) patients of the single group with TLR4 +896AG or GG and 29 of 67 (43%; (95% CI 31 to 56)) patients with AA were in remission (p = 0.001). DAS28 of the single group with TLR4 +896AG or GG was higher than with AA (p = 0.019). In the combination group, remission rates and DAS28 values were comparable between the genotypes. The polymorphic TLR4 +896G allele may impair treatment response to single DMARD treatment in recent-onset rheumatoid arthritis.
15695537 Association of polymorphism in the transforming growth factor {beta}1 gene with disease ou 2005 Aug OBJECTIVE: To investigate whether polymorphism in the transforming growth factor beta1 (TGFbeta1) gene is associated with disease outcome in rheumatoid arthritis. METHODS: 208 patients with established rheumatoid arthritis were genotyped for the TGFbeta1 T869C polymorphism using an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Disease severity was assessed by measuring radiographic damage by Larsen score and functional outcome by the health assessment questionnaire (HAQ). Patients were tracked on the NHS central register for notification of death, and the relation between TGFbeta1 polymorphism and mortality was analysed using Cox proportional hazards regression. RESULTS: Patients carrying a TGFbeta1 T allele had a higher mean HAQ score than those without this allele (1.60 v 1.22, p = 0.04). The T allele was also associated with higher five year mean area under the curve (MAUC) erythrocyte sedimentation rate (ESR), and nodular disease. Larsen score was higher in patients with the TT genotype compared with CC + CT genotypes, although this was not significant after correction for disease duration. There was a trend of increasing mortality risk with T allele dose after adjustment for age, sex, and disease duration (hazard ratio = 1.6 (95% confidence interval, 1.1 to 2.4), p = 0.01). CONCLUSIONS: TGFbeta1 T869C gene polymorphism is associated with disease outcome in rheumatoid arthritis. Carriage of the T allele (putatively associated with decreased TGFbeta1 production) was associated with increased inflammatory activity and poor functional outcome, while increasing T allele dose was associated with worse survival.
16838903 [Eye involvement in rheumatoid arthritis in children and adults]. 2006 Jun Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are systemic autoimmune diseases characterized by synovitis and a wide range of extraarticular manifestations. Ocular involvement occurs frequently in both diseases and it may affect all layers of the eyes. This review summarizes the clinical manifestations, the diagnostic tools and the therapeutic modalities of the various ocular features of patients with juvenile and adult rheumatoid arthritis.
16078315 Evaluation of the MDHAQ in Finnish patients with RA [corrected]. 2005 Aug OBJECTIVE: To study the characteristics of the Multidimensional Health Assessment Questionnaire (MDHAQ) in Finnish patients with rheumatoid arthritis. METHODS: The reliability of the questionnaire was tested by test-retest procedure. Construct validity was studied by factor analysis and convergent validity by calculating correlations between the Finnish MDHAQ (Finn-MDHAQ) scales and the Finnish Health Assessment Questionnaire (HAQ) and the Finnish Arthritis Impact Measurement Scales (Finn-AIMS2). Correlations between Finn-MDHAQ and measures of clinical characteristics, disease activity, and functional class were also measured. An item analysis was made of the Finn-MDHAQ scales Function (FN) and Psychological (PS). RESULTS: Internal consistency on the FN scale was 0.92 (95% lower limit 0.89) and 0.66 (0.56) on the PS scale. Reproducibility (95% CI) on FN was 0.93 (0.82 to 0.97) and on PS 0.84 (0.70 to 0.92). Factor analysis identified 2 factors, mobility of upper extremities and trunk, and mobility of lower extremities. Strong correlations were found between the FN scale and HAQ and physical subscales of Finn-AIMS2 and between PS and the psychological subscales of Finn-AIMS2. In item analysis corrected item correlation was high on the Finn-MDHAQ scales, except in one item on the PS scale. CONCLUSION: The Finn-MDHAQ is an applicable, reliable, and valid instrument for the part of the FN scale measuring functional ability in Finnish rheumatic patients. The incongruity in the PS scale structure that produced moderate internal consistency can be overcome with minor modifications.
16970509 Disease-modifying antirheumatic drugs in pregnancy: current status and implications for th 2006 Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD at time of conception as well as during pregnancy. The aim of this paper was to review recent literature about DMARDs used for rheumatic diseases in pregnancy and to describe the type of study designs and results reported.Twenty-nine studies; eight on hydroxychloroquine/chloroquine, thirteen on methotrexate, three on sulfasalazine and six on azathioprine were identified. With respect to hydroxychloroquine, most studies concluded that it could be safely used in systemic lupus erythematosus or RA. The same conclusions were drawn from the azathioprine studies, but the available evidence is scarce. Although the evidence regarding the safety of methotrexate during pregnancy is conflicting, a high rate of pregnancy losses indicates a risk to the fetus. For each individual case it must be decided whether the benefits outweigh the potential risks. No major teratogenic effects of sulfasalazine were seen although teratogenic effects still can not be excluded. For all other DMARDs, the information on their use in pregnancy was limited. This review underscores the gross absence of data on safety and risks of DMARD use during conception and pregnancy. While young women use these drugs in pregnancy, this review stresses the importance of good monitoring and further research.
16645970 Followup radiographic data on patients with rheumatoid arthritis who participated in a two 2006 May OBJECTIVE: In a previous clinical trial of patients with early rheumatoid arthritis (RA), it was determined that patients who received 10 mg of prednisone per day for 2 years had less radiographic joint damage compared with those who received placebo. Our goal was to investigate whether this beneficial effect persisted after the end of the trial. METHODS: A blinded assessment of radiographic joint damage was performed approximately 3 years after the end of the original 2-year study. Twenty-four patients from the original prednisone group (60%) and 28 patients from the original placebo group (68%) participated in this followup study. At the end of the original trial, prednisone dosages were tapered down in the prednisone group and stopped, if possible. Patients from the original prednisone group took prednisone during 35% of the followup period (approximately 1 year) at a mean daily dose of approximately 5 mg. Two patients from the original placebo group started taking prednisone during followup. Radiographs of the hands and feet were scored according to the van der Heijde modification of the Sharp method. RESULTS: During 3 additional years of followup, radiographic scores showed significantly less progression in the original prednisone group than in the original placebo group. Radiographic damage in the original prednisone group did not show an accelerated rate of progression during the followup period. CONCLUSION: The inhibition of radiographic joint damage in patients with early active RA treated with 10 mg of prednisone per day for 2 years seems to persist after the end of prednisone therapy.
16889046 [An AA-amyloidosis course in patients with rheumatoid arthritis]. 2006 AIM: To characterize renal amyloidosis in patients with rheumatoid arthritis and stages of amyloid nephropathy. MATERIAL AND METHODS: The trial covered 30 patients (6 males and 24 females) with documented rheumatoid arthritis (RA) complicated with secondary AA-amyloidosis. Amyloidosis diagnosis was confirmed in all the patients morphologically, the samples were studied with the peroxidase immunohistochemical method using specific monoclonal antibodies to SAA. Clinical manifestations of RA were assessed by the disease activity, functional impairment of the joints, x-ray alterations, extraarticular signs of RA, etc. All the patients were examined clinically, total blood count and biochemical tests were made. RESULTS: In 23 (77%) of 30 examinees with RA, proteinuria as the first clinical symptom of AA-amyloidosis emerged with the first 15 years of RA. RA of the second-third degree of activity were diagnosed in 25 (83%) patients, 21 (70%) patients had apparent destructive changes in the joints (x-ray stage III-IV). Severe functional insufficiency of the joints was observed in 25 (83%) patients, deformation of the joints - in 27 (90%) patients. Clinically, renal amyloidosis was characterized by change of stages - from moderate proteinuria to nephrotic syndrome and renal failure. Prognosis of amyloid nephropathy in RA depends on duration of the proteinuric stage: if this stage is short (3 years maximum), the prognosis is worse than in its long duration. CONCLUSION: RA ranks first among causes of secondary AA-amyloidosis. Development of AA-amyloidosis in RA patients is most probable in the first 15 years of the course of the articular process. Amyloidosis is more frequent in patients with severe clinical manifestations of RA.
16022568 CCR1 antagonists in clinical development. 2005 Jul Chemokines (chemotactic cytokines) are a family of low-molecular-weight proteins that direct the cellular migration of leukocytes by binding to and activating the G protein-coupled receptors displayed on the leukocyte cell surface. The inadvertent or excessive generation of chemokines has been associated with the inflammatory component of several disease processes, and consequently, considerable efforts have been made to characterise chemokine/chemokine receptor interactions with the ultimate aim of therapeutic intervention. This review focuses on the biology of CC chemokine receptor 1, which together with its ligands is thought to recruit leukocytes during the progression of rheumatoid arthritis, multiple sclerosis and organ transplant rejection. The developments made in antagonising this receptor and efficacies of these compounds in the clinical setting are also highlighted.
17009230 Disconnect between inflammation and joint destruction after treatment with etanercept plus 2006 Oct OBJECTIVE: To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. METHODS: Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity x treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. RESULTS: GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. CONCLUSION: Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA.
16284095 Hand bone loss in early undifferentiated arthritis: evaluating bone mineral density loss b 2006 Jun OBJECTIVES: (1) To examine the change in regional bone mineral density (BMD), including the hands, and assess its role as a predictor of outcome in patients presenting with an early undifferentiated inflammatory arthritis; (2) to examine for associations with the changes in hand BMD. METHODS: 74 patients with undifferentiated hand arthritis of less than 12 months' duration were examined at baseline and then at three, six, and 12 months follow up, including BMD measurement of the femoral neck, spine (L2-4), and the whole hands using dual energy absorptiometry (DXA). RESULTS: During the study, 13 patients were diagnosed as having rheumatoid arthritis, 19 as having inflammatory non-rheumatoid joint disorders, and 42 as having non-inflammatory joint disorders. At the femoral neck and lumbar spine no significant bone loss was seen in any of the three subgroups. At the 12 months follow up the mean (95% confidence interval) hand BMD loss in the patients with rheumatoid arthritis was -4.27% (-1.41 to -7.13); in the inflammatory non-rheumatoid group, -0.49% (-1.33 to +0.35); and in the non-inflammatory joint disorder group, -0.87% (-1.51 to -0.23). In a multivariate linear regression model (including age, rheumatoid factor, mean C reactive protein, mean HAQ score, and cumulative glucocorticoid dose), only mean C reactive protein (p<0.001) and rheumatoid factor (p = 0.04) were independently associated with change in hand BMD during follow up. CONCLUSIONS: Hand DXA provides a very sensitive tool for measuring bone loss in early rheumatoid arthritis and may be useful in identifying patients at high risk of developing progressive disease. Further studies are needed to evaluate the role of hand bone loss as a prognostic factor and outcome measure in rheumatoid arthritis.
17007293 [Impacted morsellized bone grafting in primary total hip arthroplasty for acetabular protr 2006 Jul Between 1991 and 2002, we performed 156 primary total hip replacements in rheumatoid arthritis patients with protrusion acetabulum. The deficient acetabulum was reconstructed with autologous and allogous morsellized bone grafts from the femoral head. MATERIAL AND METHODS: Group 1 were 26 patients with reconstruction acetabulum deficient with autologous morsellized bone grafts and group 2 were 10 patients in witch we use allogous grafts. All patients were reviewed at an average follow-up of 5 years. The function of operated hips was determining according WOMAC, HHS and Merle-d'Aubigne-Postela scores. Incorporation of grafts was assessing according to Avci criteria. RESULTS: We found similarly good and very good results in both groups. Incorporation of allo- and auto- bone grafts was observed after average 26 months. In 1 hip we found porotic grafts but without of loosening of the acetabular component. CONCLUSION: This technique is a good option in cases with protrusion acetabulum due to rheumatoid arthritis.
16541759 [Case of rheumatoid arthritis with various histological lesions of the kidney]. 2006 We experienced a case of rheumatoid arthritis with nephrotic syndrome. A renal biopsy specimen from this patient showed various renal histological changes. The patient was a 50-year-old man who was diagnosed as having rheumatoid arthritis in 1987. We performed a renal biopsy because he had persistent proteinuria from March in 2002. The renal biopsy specimen showed amyloid AA and P protein deposition in the glomeruli. Moreover mild mesangial proliferation was recognized. IgA-deposition in the mesangial area, and granular-deposition of IgG along the glomerular capillary wall were also observed. In electron microscopy, electron dense deposits were recognized in the mesangial area and subepithelium of the glomerular basement membrane. From these findings, we diagnosed amyloid nephropathy, IgA nephritis and membranous nephropathy. Renal biopsy of patients with RA is useful not only for precise diagnosis, but also for selection of the appropriate treatment.
16200610 Association of HLA-DR3 with anti-cyclic citrullinated peptide antibody-negative rheumatoid 2005 Oct OBJECTIVE: Recent data have shown that the most prominent and longest known genetic risk factors for rheumatoid arthritis (RA), HLA-DRB1 shared epitope alleles, are only associated with RA that is characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP antibodies) and not with anti-CCP-negative RA. We undertook this study to investigate whether anti-CCP-negative RA is associated with other HLA-DRB1 alleles. METHODS: HLA typing was performed for 377 patients from the Leiden Early Arthritis Clinic who were diagnosed as having RA within the first year of followup (206 anti-CCP-positive patients and 171 anti-CCP-negative patients), 235 patients who, after 1 year, had undifferentiated arthritis (UA) (28 anti-CCP-positive patients and 207 anti-CCP-negative patients), and 423 healthy control subjects. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for HLA-DRB1 allele frequencies were determined for all patient groups compared with the healthy control group. RESULTS: HLA-DR3 was more frequently present in the anti-CCP-negative RA group than in the control group (OR 1.84, 95% CI 1.26-2.67). This was not the case for anti-CCP-positive RA (OR 0.92, 95% CI 0.60-1.40). HLA-DR3 was also more frequently present in anti-CCP-negative UA patients (OR 1.59, 95% CI 1.10-2.28), but not in anti-CCP-positive UA patients (OR 0.68, 95% CI 0.17-1.92). CONCLUSION: HLA-DR3 is associated with anti-CCP-negative arthritis and not with anti-CCP-positive arthritis. These data show that distinct genetic risk factors are associated with the presence of anti-CCP antibodies in RA and indicate that different pathogenetic mechanisms underlie anti-CCP-positive and anti-CCP-negative RA.
17471832 [Rational therapeutic approach in rheumatoid arthritis]. 2006 The natural course of rheumatoid arthritis inevitably leads to joint damage and reduced life expectancy. Therefore, active treatment of rheumatoid arthritis is indispensable. Although the etiology still remains unknown resulting in unsuccessful prophylaxis and incurability of rheumatoid arthritis, learning more about its pathophysiology broadens the spectrum of therapeutic possibilities. The aim of treatment is remission of the disease. Current standards of treatment are based on the idea to start aggressive treatment as early as possible to suppress the activity of the disease. This can be achieved by pharmacotherapy and rehabilitation. Physiotherapy is supplementary but there is no room for spa treatment or alternative therapies. Treatment should be introduced immediately because the "window" for successful change in the natural course of the disease covers the first three months since onset. Diagnostic difficulties during this period support the idea of "early arthritis" and "early rheumatoid arthritis". Glycocorticosteroids at a dose suitable to suppress inflammation represent the first-line treatment. Basic therapy which usually is synonymous for methotrexate 15-25 mg once weekly should be introduced from the 4th month at the latest. In case of methotrexate intolerance, leflunomide is an alternative. Lack of efficacy of monotherapy with these drugs mandates the combination therapy of methotrexate with leflunomide, cyclosporine or sulphasalazine together with hydroxychlorochine. The use of two latter drugs should be limited due to their low efficacy. Patients refractory to combination therapy should be considered as candidates to anticytokine drugs or to lymphocyte B depleting drugs. However, it should be emphasized that their high efficacy is achieved only in combination with full doses of methotrexate. The same rules should be applied to therapeutic decisions in elderly patients and in patients with long history of rheumatoid arthritis. However, lower doses of the drugs should be used at initiation of therapy. Contraindications related to side effects and concomitant diseases should be considered. In these groups, glycocorticosteroids play a more important role and cyclophosphamide is used more frequently. Surgical treatment should be reserved for patients with advanced disease. Total joint replacement is an effective method for large joints. Synovectomy should be done only exceptionally when all options of pharmacotherapy were ineffective.
15818709 Successful treatment with intraarticular infliximab for resistant knee monarthritis in a p 2005 Apr Positive experiences with intraarticular infliximab have been reported in patients with rheumatoid arthritis, ankylosing spondylitis, and Behcet's disease. We used intraarticular infliximab to treat resistant knee monarthritis in a patient with spondylarthropathy. Clinical and laboratory improvement was associated with improvement in scintigraphic findings. This approach is less expensive than intravenous administration of infliximab. We suggest that selection of candidates for this innovative therapy should be guided by anti-tumor necrosis factor alpha scintigraphy.
16881355 [An antidestructive effect of leflunomide in early rheumatoid arthritis]. 2006 AIM: To study effects of leflunomide on inflammatory and destructive processes in patients with early rheumatoid arthritis (RA). MATERIAL AND METHODS: The trial included 33 patients (27 females and 6 males) with a significant diagnosis of RA (A CR criteria) aged 19 to 60 years and duration of the disease from 6 months to 3 years (15.97 +/- 9.70 months). The activity of the inflammatory process and treatment efficacy were assessed by severity of the articular syndrome, duration of morning stiffness (DMS), pain and the disease activity (VAS), device examination, the disease activity by DAS28 indices, etc. The articular syndrome was assessed by the number of painful joints (NPJ), number of swollen joints (NSJ), etc. The functional status of the patient was evaluated by Keitel test, HAQ and hand grip. Calculations were made of erosive arthritis progression rate (EAPR) and joint fissure narrowing progression rate (FNPR). All the patients received leflunomide (100 mg/day for 3 days, then 20 mg/day). A 12-month course was finished by 14 patients, 4 patients were withdrawn because of side effects, the rest--by social causes. RESULTS: To the end of the trial leflunomide reduced NPJ by 84%, NSJ--by 95%, DMS--by 88%, articular pain by VAS--by 66%, the disease activity by VAS--by 70%. A positive trend in DAS28 criterium was observed (a significant suppression of RA activity after 1 month of therapy by 18%, after 4 months--by 39%, after 6 months--by 43%, by the end of the treatment--by 48%). For the initial 6 months EAPR was 0.50 +/- 0.67, for the following 6 months it lowered to 0.37 +/- 1.00, while FNPR decreased to 1.14 +/- 1.26 vs. 1.31 +/- 2 58 for initial 6 months. A positive change of the level of type 3 matrix metalloproteinase (a 20% and 16% by month 4 and to the end of the trial, respectively) was registered. CONCLUSION: A positive effect of leflunomide on RA inflammatory activity and progression rate of joint destruction was confirmed.
16673133 HLA-DRB1 association in Saudi rheumatoid arthritis patients. 2006 Sep Association between HLA-DRB1 alleles and rheumatoid arthritis (RA) has been known for more than three decades. However, the strength of these links varies between ethnic groups. This study examines the frequency of HLA-DRB1 alleles amongst Saudi RA patients. The DRB1 region of major histocompatibility complex was screened by polymerase chain reaction/sequence specific primers (PCR/SSP) in a total of 140 subjects including 70 RA patients and 70 matched healthy controls. HLA-DRB1 *04 was found to be the most frequent allele associated with RA followed by DRB1 *08 and DRB1 *10. On the other hand, the frequency of DRB1*06 was found to be decreased in RA patients as compared to controls. Molecular sub typing of the most prevalent allele DRB1 *04 revealed a statistically significant association between RA and DRB1 *0405. We conclude that an improved understanding about the influence of HLA on RA might help in predicting the susceptibility or protection against disease.
16571284 Effect of Yangqixue Qufengshi Recipe on rheumatoid arthritis model mice under different ge 2006 Mar OBJECTIVE: To study the effect of Yangqixue Qufengshi Recipe (YQXQFS) on rheumatoid arthritis (RA) model mice under different genetic backgrounds. METHODS: Collagen Induced Arthritis (CIA) were established on HLA-DR4 transgenic (TG) mice and non-transgenic (NTG) mice, which partly were raised with YQXQFS, and the onset day of CIA, the level of type II collagen (CII)-reactive antibodies and the pathological scores of CIA were assessed. RESULTS: Under HLA-DR4 TG background (compared with NTG mice), the earlier onset day of CIA (11.22 +/- 3.35 days vs 16.56 +/- 4.75 days, P < 0.05) and higher level of CII-reactive antibodies (0.2274 +/- 0.1390 microg/ml vs 0.1101 +/- 0.0560 microg/ml, P < 0.05) were observed, but the pathological scores of CIA remained unchanged. YQXQFS could not influence the onset day of CIA and the level of CII-reactive antibodies, but had a certain effect on the total pathological scores (6.56 +/- 3.43 scores vs 11.11 +/- 5.64 scores) and bone erosion (0.22 +/- 0.44 scores vs 1.67 +/- 1.50 scores) of CIA on NTG mice (P < 0.05), NTG YQXQFS group compared with NTG experimental group. CONCLUSION: YQXQFS had a certain effect on RA model, but had no significant effect on HLA-DR4 related CIA.
16447239 Reconstitution of peripheral blood B cells after depletion with rituximab in patients with 2006 Feb OBJECTIVE: To study the quantitative and phenotypic reconstitution of peripheral blood B cells and its relationship to the dynamics of clinical response in patients with rheumatoid arthritis (RA) following B cell depletion with rituximab. METHODS: Twenty-four patients with active RA treated with rituximab were studied. Flow cytometry with combinations of monoclonal antibodies to B cell and T cell subsets was used. RESULTS: The frequency and total number of CD19+ cells in the peripheral blood decreased a mean of 97% for more than 3 months in all but 1 patient following rituximab therapy. All B cell populations were depleted. More than 80% of residual B cells showed a memory or plasma cell precursor phenotype. B cell repopulation occurred a mean of 8 months after treatment and was dependent on the formation of naive B cells, which showed an increased expression of CD38 and CD5. During repopulation, increased numbers of circulating immature B cells, CD19+,IgD+,CD38(high),CD10(low),CD24(high) cells, were identified. Patients who experienced a relapse of RA on return of B cells tended to show repopulation with higher numbers of memory B cells. A small number of T cells and natural killer cells expressed low levels of CD20. These cells were depleted following rituximab therapy and returned to the circulation a mean of 5 months after treatment. No other significant changes were detected in the T cell populations studied. CONCLUSION: Rituximab induced a profound depletion of all peripheral blood B cell populations in patients with RA. Repopulation occurred mainly with naive mature and immature B cells. Patients whose RA relapsed on return of B cells tended to show repopulation with higher numbers of memory B cells.