Effectiveness and safety of Chinese herbal formula combined with western medicine for ankylosing spondylitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease of the spine, which mainly invades the sacroiliac joint, spine, and large joints near the trunk, leading to fibrous and skeletal ankylosis and deformity, and can cause damage to the eyes, lung, cardiovascular, kidney and other organs. Chinese herbal formulas (CHF) is an important interventions of Traditional Chinese Medicine (TCM), and CHFs combined with western medicine are widely used in clinical practice to treat AS. METHODS: Eight databases will be systematically retrieved from their inceptions to March 2021. Only randomized controlled trials (RCTs) of CHFs combined with western medicine for AS treatment will meet the inclusion criteria. The primary outcomes we focus on include clinical effectiveness rate, TCM syndrome score, TCM symptom score, Bath ankylosing spondylitis disease activity index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), chest expansion, nocturnal spinal pain, adverse reactions, erythrocyte sedimentation rate (ESR), and C protein response (CRP). The research screening, data extraction, and risk of bias assessment will be performed independently by 2 researchers, and divergence will be solved by a third researcher. Revman 5.3 software will be used for meta-analysis. The confidence of evidence will be graded using grading of recommendations assessment, development, and evaluation (GRADE) algorithm and methodological quality will be assessed adopting risk of bias in systematic reviews (ROBIS). RESULTS: This systematic review (SR) will provide evidence-based medical evidence for AS therapy by CHF combined with western medicine and we will submit the findings of this SR for peer-review publication. CONCLUSIONS: This SR will provide latest and updated summary proof for assessing the effectiveness and safety of CHF combined with western medicine for AS. REGISTRATION NUMBER: INPLASY 202150089.

Biologics in Inflammatory and Immunomediated Arthritis.

BACKGROUND: Biologic drugs, introduced in clinical practice almost twenty years ago, represent nowadays a prominent treatment option in patients with chronic inflammatory arthritis, such as Rheumatoid Arthritis, Psoriatic Arthritis and Spondyloarthritis, that include ankylosing spondylitis and non-radiographic axial spondyloarthritis. METHODS: Several compounds targeting different pathways have been marketed and approved for the treatment of inflammatory arthritis, with a significant impact on the clinical outcomes and the natural history of the diseases. RESULTS: There are currently seven classes of biologics that are available for the treatment of inflammatory arthritis, each inhibiting a different aspect of the immune-driven inflammatory pathway. They include: • Tumor Necrosis Factor (TNF) inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol); • Interleukin-1 (IL-1) receptor antagonists (anakinra); • Interleukin-6 (IL-6) inhibition (tocilizumab); • Interleukin-12/23 (IL23) inhibition (ustekinumab); • Interleukin-17 (IL-17) inhibition (secukinumab); • B-cell inhibition (anti-CD20, rituximab); • T-cell costimulation inhibition (anti-CTLA-4, abatacept). CONCLUSION: In this review, we will focus on the role of biologic drugs in the treatment strategies for inflammatory arthritis.

Biologic Therapies for Autoimmune and Connective Tissue Diseases.

Biologic therapy continues to revolutionize the treatment of autoimmune disease, especially in rheumatology as the pathophysiology of both inflammation and autoimmune disease becomes better understood. These therapies are designed to dampen the response of the inflammatory cascades. Although the first biologic therapies were approved many years ago, expanding indications and new agents continue to challenge the traditional treatment strategies for rheumatic diseases. This article reviews the data supporting the current use of biologic therapies, including off-label indications, in a subset of rheumatic diseases including rheumatoid arthritis, lupus, inflammatory myositis, ankylosing spondylitis, psoriatic arthritis, vasculitis, and gout.

A Retrospective Cohort Study Comparing Utilization and Costs of Biologic Therapies and JAK Inhibitor Therapy Across Four Common Inflammatory Indications in Adult US Managed Care Patients.

INTRODUCTION: Biologic therapies are used to treat several inflammatory diseases, including rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Data from a commercial claims database were used to evaluate utilization and cost of biologic treatment for these conditions. METHODS: Data were obtained from the Optum Research Database. Patients were aged 18-63 years with diagnosis of moderate to severe RA, PsO, PsA, and/or AS and first (index) claim for biologics abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab, or ustekinumab or non-biologic tofacitinib between March 1, 2011 and February 28, 2013. One-year treatment costs were based on observed paid amounts and used to impute dosing. Treatment patterns (persistence, switching, discontinuing, restarting) were evaluated. RESULTS: Data from 20,159 patients were analyzed for index medications abatacept (n = 583), adalimumab (n = 6521), certolizumab pegol (n = 415), etanercept (n = 9116), golimumab (n = 231), infliximab (n = 1906), rituximab (n = 295), tocilizumab (n = 165), ustekinumab (n = 922), and tofacitinib (n = 5). For patients with RA only, costs were lowest for tofacitinib ($18,769), rituximab ($19,569), or abatacept ($21,877), and ranged from $23,682 to $30,269 for all other medications. For patients with PsO only, costs were lowest for adalimumab ($29,186), etanercept ($31,212), and infliximab ($32,409) compared with ustekinumab ($53,746). For patients with PsA only, costs were lowest for etanercept ($26,916), followed by golimumab ($27,987), adalimumab ($28,749), and infliximab ($31,974). Costs were lowest with etanercept for RA plus PsA ($25,477) and for PsO plus PsA ($29,376), and with golimumab for AS only ($24,225). Across indications, annual costs were $29,521, $27,488, and $28,672 for adalimumab, etanercept, and infliximab, respectively; persistence was greatest with infliximab (range 66-79%) compared with 11-59% for all other biologics. CONCLUSION: One-year treatment costs varied considerably between medications and indications. Some newly approved agents had lower costs but further research is needed to confirm these estimates as more patients are treated. FUNDING: Immunex (a wholly owned subsidiary of Amgen Inc.) and Wyeth (acquired by Pfizer).

[Effect of Xinfeng Capsule on Related Factors of Thrombus Formation and Inflammatory Cytokines in Active Ankylosing Spondylitis Patients].

Objective To observe the effect of Xinfeng Capsule (XFC) on related factors of thrombus formation and inflammatory cytokines in active ankylosing spondylitis (AS) patients. Methods Seventy-six active AS patients were assigned to the XFC group and the Sulfasalazine treated group (SASP group) , 38 in each group according to random digits table. Patients in the SASP group took SASP, 0. 25 g per tablet, 4 tablets each time, twice per day. Those in the XFC group took XFC, 0. 5 g per pill, 3 pills each time, three times per day. All medication lasted for 12 successive weeks. Platelet count and coagulation functions were determined. Factors of thrombus formation [including thromboxane B2(TXB2), prostaglan- din 12 (PG12), 6-ketone-prostaglandin F1 (6-keto-PGF1) , platelet granular membrane protein140 (GMP140), plasminogen activator inhibitor 2 (PAI-2 ) ], erythrocyte sedimentation rate (ESR), C reactive protein (CRP) , and levels of cytokines (TNF-α, IL-4, IL-10, IL-17) were detected. mRNA expressions of nuclear factor activator (Act1) , NF-κB inhibitory protein-alpha (IKBα) , inhibitor of kappa-B kinase beta (IKKß) , NF-κB protein 65 (NF-κB/P65), and NF-κB protein 50 (NF-κB/P50) were detected by real-time fluorescent quantitative PCR (RT-PCR). Meanwhile, the protein expression of NF-κB/P65 and NF-κB/P50 were detected by Western blot. Results Compared with before treatment in the same group, levels of PLT, fibrinogen (FBG), D-dimer (DD), TXB2, GMP140, and PAI-2 were significantly decreased, but 6-keto-PGF1 level was significantly increased in XFC group after treatment (P <0. 01). Besides, the improvement of above indices was significantly superior in the XFC group to SASP group in the same period (all P <0. 01). Compared with before treatment and SASP group after treatment, IL-17 level was significantly decreased, IL-4 and IL-10 were significantly increased, levels of ESR and CRP decreased in the XFC group after treatment (P <0. 05, P <0. 01). Compared with before treatment in the same group, mRNA expressions of Act1, IKKß, IKBα, NF- κB/P50, and NF-κB/P65, and protein expressions of NF-κB/P65 and NF-κB/P50 were obviously reduced in the two groups after treatment (P <0. 05, P <0. 01). Besides, mRNA expressions of lKKß, IKBα, NF-κB/ P50, and NF-κB/P65, and protein expressions of NF-κB/P65 and NF-κB/P50 were more obviously reduced in the XFC group than in the SASP group (P <0. 05, P <0. 01). Conclusions XFC could improve thrombosis re- lated factors in AS patients. Its mechanism might be associated with regulating cytokines and inhibiting ex- cessive activation of NF-κB signal pathway.

IL-6 as a keystone cytokine in health and disease.

Interleukin 6 (IL-6) has a broad effect on cells of the immune system and those not of the immune system and often displays hormone-like characteristics that affect homeostatic processes. IL-6 has context-dependent pro- and anti-inflammatory properties and is now regarded as a prominent target for clinical intervention. However, the signaling cassette that controls the activity of IL-6 is complicated, and distinct intervention strategies can inhibit this pathway. Clinical experience with antagonists of IL-6 has raised new questions about how and when to block this cytokine to improve disease outcome and patient wellbeing. Here we discuss the effect of IL-6 on innate and adaptive immunity and the possible advantages of various antagonists of IL-6 and consider how the immunobiology of IL-6 may inform clinical decisions.

Golimumab, the newest TNF-α blocker, comes of age.

Golimumab, a fully human monoclonal antibody against tumour necrosis factor-α (TNF-α) is one of the newest biologics that has become available for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Following the initial randomised double-blind placebo-controlled clinical trials, which demonstrated the efficacy and safety of the drug in the context of a limited patient sample and a relatively short time frame, golimumab has been the focus of continuous investigation through the extensions of the above-mentioned trials, new clinical trials and registries of biologic drug use in daily clinical practice. The review of this data and their inclusion in meta-analyses and indirect comparisons across TNF-α blockers suggest that golimumab possesses similar properties regarding efficacy and safety as the older monoclonal anti-TNF-α antibodies. The novelty of golimumab is perhaps its dosing regimen, i.e. subcutaneous self-administration once monthly, which allows for the least disturbance in the life of patients.

[The effect of Xinfeng capsule treatment on the number of BTLA(+)T cells and oxidative stress of patients with ankylosing spondylitis].

OBJECTIVE: To investigate the changes of B and T lymphocyte attenuator (BTLA), reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total antioxidative capacity (TAOC) in the patients with ankylosing spondylitis (AS) and the effect of Xinfeng capsule (XFC) on them. METHODS: AS patients (n=140) were randomly divided into two groups, XFC group (3 tablets each time, tid, n=70) and salicylazosulfapyridine (SASP) group (4 pills each time, bid, n=70). Continuous treatment lasts 3 months. The study also enrolled 60 healthy volunteers as a control group. Flow cytometry was used to test BTLA expression. ELISA was performed to detect the oxidative stress indicators (ROS, RNS, MDA, SOD, CAT, TAOC) and cytokines (IL-4, IL-10, IL-1ß, TNF-α). Western blotting was adopted to examine the blood sedimentation (ESR). HITACHI 7060 automatic biochemical analyzer was used to determine the level of high sensitive C-reactive protein (Hs-CRP). RESULTS: Clinical efficacy of XFC group was significantly better than that of SASP group (P<0.01). Compared with the healthy control group, AS patients had significantly lower BTLA expression in CD3(+) T cells and CD4(+) T cells from the peripheral blood (P<0.01 or P<0.05), the decreased levels of SOD, CAT and TAOC, and significantly increased ROS, RNS and MDA values (P<0.01 or P<0.05). In addition, the levels of serum IL-1ß, TNF-α, ESR and Hs-CRP were significantly higher (P<0.01) and IL-4, IL-10 were significantly lower in AS patients (P<0.01 or P<0.05). Compared with pre-treatment, both XFC and SASP significantly elevated the expressions of BTLA(+)CD3(+) T, BTLA(+)CD4(+) T, BTLA, SOD, TAOC, IL-4, SF-36 (PF, SF, RP, RE, BP, MH, VT, GH) eight dimension scores, and reduced ROS, MDA, TNF-α, ESR, Hs-CRP, VAS, BASDAI, BASFI and BAS-G in the peripheral blood (P<0.01 or P<0.05). The differences between XFC group and SASP group were statistically significant (P<0.01 or P<0.05). Pearson correlation analysis showed that BTLA expression level in the peripheral blood was positively correlated with SOD, RP, BP, SF and RE. BTLA(+)CD3(+) T cells and BTLA*CD4(+) T cells were significantly negatively correlated with ROS, MDA, IL-1ß, TNF-α, ESR, VAS and BASDAI, and they were positively correlated with TAOC, IL-4 and IL-10. BTLA(+)CD3(+) T cells were significantly negatively correlated with RNS, Hs-CRP and BASFI; BTLA(+)CD4(+) T cells were positively correlated with CAT. CONCLUSION: XFC can improve BTLA expression in the peripheral blood of AS patients and regulate negatively the activation and proliferation of T cells.

Effects of icariin on cytokine-induced ankylosing spondylitis with fibroblastic osteogenesis and its molecular mechanism.

The aim of this study is to explore the effects of icariin on cytokine induced ankylosing spondylitis fibroblast osteogenesis type expression and its molecular mechanism. The normal fibroblasts were collected as normal control group, and the fibroblasts of hip joint capsule of AS patients were collected, which were respectively added in fetal bovine serum (group AS), fetal bovine serum and cytokines (BMP-2+TGF-beta 1) (group AS), and cell factor solution (icariin group), and observed of the osteogenic expression of fibroblast, to evaluate the impact of Icariin on it. The ALP activity, the content of collagen, osteocalcin content and cbfa1mRNA and OCmRNA of fibroblast of AS group increased compared to the normal control group and AS control group (P < 0.01), indicating that icariin can significantly inhibit the above changes (P < 0.01). Icariin can inhibit fibroblast further osteogenic differentiation through inhibiting the effect of cytokines on the fibroblast osteogenesis type markers and osteogenic gene expression and osteogenic differentiation.

The efficacy and safety of Jitongning Capsule () in patients with ankylosing spondylitis.

OBJECTIVE: To confirm the efficacy and safety of Jitongning Capsule in the treatment of ankylosing spondylitis (AS). METHODS: A total of 120 AS patients with early-intermediate were randomly and equally assigned to Jitongning Capsule group and sulfasalazine group. Jitongning Capsule was orally taken 4.5 g per day and sulfasalazine was orally taken 2 g daily for 12 months. The primary endpoint was the proportion of patients achieving the Assessment in Ankylosing Spondylitis 20 (ASAS 20), secondary end points included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), patient's global assessment by VAS rating, spinal pain, general pain and night pain, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) in the peripheral blood mononuclear cells (PBMC) of AS patients were measured. RESULTS: A total of 111 patients completed the study. There were 58 patients in Jitongning group and 53 patients in sulfasalazine group. Both drugs showed mild and occasional side effects. After treated by Jitongning Capsule and sulfasalazine, the proportion of ASAS20 responders at 12 month was 72.41% (42/58) and 67.92% (36/53) respectively. Both Jitongning Capsule and sulfasalazine treatment induced significant decrease in the proportion of CD4(+)T cell and CD8(+)T cell expressing TNF-α and IFN-γ at 12-month of treatment compared with baseline values (P<0.05). CONCLUSION: Jitongning Capsule are effective in a setting close to real-life medical care with a sustained improvement in signs and symptoms of AS, and reduce cytokine levels in PBMC. It showed comparable effects to sulfasalazine.

The effect of neutralizing antibodies on the sustainable efficacy of biologic therapies: what's in it for African and Middle Eastern rheumatologists.

Over the last decade, biologic therapeutic proteins have advanced the treatment of diseases such as rheumatoid arthritis (RA). Therapeutic antibodies such as infliximab, adalimumab, rituximab, tocilizumab, golimumab, certolizumab pegol, the receptor construct etanercept, and abatacept, an anticluster of differentiation (CD)80/anti-CD86 fusion protein, are used as treatment for RA and ankylosing spondylitis (AS). Infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept are inhibitors of tumor necrosis factor (TNF), a key regulator of inflammation. Left untreated, progression of rheumatic diseases due to inflammation can lead to irreversible joint damage and serious disability. One limitation for the use of therapeutic antibodies is immunogenicity, the induction of antibodies by the adaptive immune system in response to foreign substances. The development of antidrug antibodies (ADAs) has a varying impact on the clinical efficacy of biologic agents for the treatment of RA and AS, depending on whether the ADAs are neutralizing or non-neutralizing. Studies have indicated that neutralizing ADAs are associated with a reduced efficacy, decreased drug survival, increased instances of dose escalation, and adverse events. Comparison studies of anti-TNF biologics have demonstrated that each drug has a different sustained efficacy profile depending on immunogenicity. The purpose of this review is to provide rheumatologists with information regarding the effect of neutralizing antibodies on the sustainable efficacy of anti-TNF biologic therapies. This information will be of value to practicing rheumatologists in Africa and the Middle East who should take into account the potential for changes in the efficacy and safety of biologic therapies and closely monitor patients under their care.

The "knowns" and "unknowns" of biologic therapy in ankylosing spondylitis.

Since the first biologic agent was tested in the treatment of ankylosing spondylitis (AS), the ability of these therapies to dramatically improve the clinical symptoms and signs of the disease was very evident. Over the past decade, 4 tumor necrosis factor-alpha inhibitors have been approved by the Food and Drug Administration for the treatment of AS. Published data include randomized controlled trials, registries and observational studies. Guidelines have also been developed for the use of biologics in AS. Although a lot is known about the use of biologics in the AS, several "unknowns" remain. Whether these agents can alter the natural history of AS if started very early in the course or whether they can prevent extra-articular manifestations are among the important unanswered questions. Most of the data summarized in this review relate to tumor necrosis factor-alpha inhibitors, and other biologic agents that have been studied are included, as well. This review also summarizes what questions remain about the use of biologics in AS and what type of studies will be required to answer them.

The use of low-dose etanercept as an alternative therapy for treatment of ankylosing spondylitis: a case series.

During recent decades, biological medications play a crucial role for treating rheumatologic disorders and thus are strongly recommended for initial treatment of ankylosing spondylitis. However, because of high cost of biological drugs, the use of these drugs has been limited. In current series, we tried to assess safety of low-dose etanercept as a common usable biological drug in patients with ankylosing spondylitis. In a case-series study, 4 men with ankylosing spondylitis were treated with low-dose etanercept (25 mg/2 weeks) plus methotrexate (10 mg/week). Safety was assessed by measuring rate of differences in severity of clinical manifestations and level of C-reactive protein (CRP). After the completion of treatment with low-dose etanercept, inflammatory low back pain and morning stiffness was reduced lower than 30 min in all patients. Only one patient had baseline high serum ESR and positive CRP that was changed to negative following treatment protocol. At one-year follow-up, all participants continued their regular treatment regimen with the etanercept survival rate 100%. Neither side effects related to drug nor clinical complications were observed within the follow-up period. Our findings suggest that low-dose etanercept (25 mg/2 weeks) has an acceptable safety and effectiveness profile in individuals with ankylosing spondylitis and can be good alternative instead of conventional therapy with etanercept (25 mg two times per week).

[Effect on content of serum inflammatory cytokines of patients with ankylosing spondylitis in early stage treated by long snake moxibustion at Governor Vessel and functional exercise].

OBJECTIVE: To explore the clinical effect and mechanism of long snake moxibustion combined with functional exercise for treatment of ankylosing spondylitis in early stage. METHODS: Seventy-eight cases of ankylosing spondylitis in early stage were randomly divided into an observation group and a control group, 39 cases in each group. The observation group was treated with long snake moxibustion from Dazhui (GV 14) to Yaoshu (GV 2) combined with functional exercise; the control group was treated with oral administration of Sulfasalazine. The effects of the two groups were observed, and contents of erythrocyte sedimentation rate (ESR), tumor necrosis factor alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1) were tested before and after treatment. RESULTS: The total effective rate of 89.7% (35/39) in the observation group, was superior to that of 76.9% (30/39) in the control group (P<0.05). The contents of ESR, TNF-alpha, and ICAM-1 showed downtrend after treatment in the both groups (P<0.05, P<0.01), and the observation group decreased more obviously (all P<0.01). CONCLUSION: Long snake moxibustion at Governor Vessel combined with functional exercise for treatment of ankylosing spondylitis in early stage, can significantly improve clinical symptoms, decrease the level of serum inflammatory cytokines, and the effect is superior to that of Sulfasalazine oral administration.

Antibodies to human tissue transglutaminase and alterations of vitamin D metabolism in ankylosing spondylitis and psoriatic arthritis.

Both in ankylosing spondylitis (ASP) and psoriatic arthritis (PsA), osteopenia is present in one-third of women and men, whereas osteoporosis mainly affects men, even in their 30 s. Subclinical gut inflammation has been described in patients with AS or PsA. Joint involvement also occurs with other gastrointestinal diseases such as celiac disease. We tested the hypothesis, whether elevated serum levels of human anti-tissue-transglutaminase-IgA (htTG) are associated with changes in disease activity, vitamin D metabolism and bone mineral density (BMD) in patients with ASP and PsA. In a cross-sectional study, we evaluated both biochemical markers of bone turnover, BMD and htTG in 76 patients with ASP and 120 patients with PsA. A reduction of BMD in lumbar spine was determined both in ASP (42.7%) and in PsA (57.3%). Furthermore, a significantly higher prevalence of htTG was detected only in ASP (14/76). ASP patients with negative htTG status have significant higher 25-vitamin D3 levels. ASP patients with positive htTG status are younger. A positive htTG status entails the risk of a bad vitamin D supply, which should be considered in young patients since this constellation favors a reduction in bone density. The coincidence of ASP along with detection of htTG and clinically asymptomatic celiac disease as an accessory source of inflammation with a negative influence on the bone metabolism is also conceivable. Clinicians need to be aware of patients younger than 45 years with ASP, which have important implications for the correct treatment and vitamin D supplementation.

[Ankylosing Spondylitis and convenient nutrition]. / Günstige Ernährung bei Morbus Bechterew.

The genetic setting and immunopathogenesis of patients with ankylosing spondylitis can not be changed by the diet. Therefore, an effective pharmacological therapy always is required. As adjuvant therapy the anti-inflammatory diet can help to reduce inflammatory processes, and to delay flares of the disease. The anti-inflammatory diet is consistent with a balanced diet and prevents infirmity provoked by malnutrition. Ankylosing spondylitis is an autoimmune disease and, as such, nutrients may mimic an antigen and cause flares of the disease and increase disease activity driven by antigen reaction. This nutrient-receptor interaction occurs in the individual patient, necessitating an individual dietary counselling for the patient with ankylosing spondylitis.

[Peloid therapy in various temperature modes in rehabilitation of patients with seronegative spondylarthritis].

Fifty patients with ankylosing spondylarthritis (AS) and 21 patients with reactive arthritis, Reiter's disease received peloid therapy. AS patients with a prevalent spinal lesion received mud applications (38-40 degrees), those with a prevalent joint lesion - applications of colder mud (22-24 degrees C), those free of inflammation in the joints and periarticular tissues - mud of 38-40 degrees C temperature. In reactive arthritis and Reiter's disease mud applications with temperature 22-24 degrees are indicated.

Ankylosing spondylitis, HLA-B27 positivity and the need for biologic therapies.

OBJECTIVES: HLA-B27 positivity strongly influences Ankylosing spondylitis (AS) disease susceptibility and phenotype. The aim of this study was to analyse an AS cohort with respect to quality of life (ASQoL), extra-articular disease, markers of disease activity (BASDAI), functional capacity (BASFI), biologic requirement, and the influence of HLA-B27 on these parameters. METHODS: Data recorded in 82 patients included demographics (age, sex), extra-articular disease (GI, ocular, dermatological, GU), cardiac and pulmonary diagnoses. BASDAI, BASFI, ASQoL, joint counts, disease duration and past/present treatment (NSAID, DMARD, steroid and biologic use) were also recorded. RESULTS: 90.2% of the cohort was B27 positive with significantly longer disease duration (17.6 v 6.9 years, p<0.05). BASFI (42.2 v 5.9), BASDAI (3.22 v 1.3), ASQoL (10 v 4), physician assessment of biologic need (24 v 5), steroid (15.7% v 12.5%) and NSAID use (98.6% v 75%) were higher in the B27 positive group, as were ocular (38.9% v 12.5%), pulmonary (4.2% v 0%) and cardiac (4.3% v 0%) features. Negative patients displayed more GI (37.5% v 19.4%), dermatological (25% v 19.7%) and GU (25% v 4.2%) features. Patients satisfying ASAS (AS assessment study group) criteria and receiving biologic therapy were 18.9% (B27 positive group) and 0% (B27 negative group). CONCLUSIONS: AS patients have significantly longer disease duration if B27 positive, higher markers of disease activity, poorer functional status, poorer quality of life, and more extra-articular manifestations. These findings were reflected in the percentage of patients needing biologic therapies.

FOXP3 identifies regulatory CD25bright CD4+ T cells in rheumatic joints.

Regulatory T cells have recently been implicated in a number of human diseases, including rheumatoid arthritis. To investigate whether the presence of CD25+CD4+ regulatory T cells is a general finding in arthritic joints, synovial fluid of patients with different rheumatic diseases such as undifferentiated arthritides, systemic rheumatic diseases and reactive arthritis were investigated for the presence of such cells. In 95% of the patients, a higher frequency of CD25(bright)CD4+ T cells was found in synovial fluid as compared with peripheral blood. Both in vitro suppression experiments and FOXP3 mRNA analysis confirmed these cells to be natural regulatory T cells. Together with our previous data, we conclude that arthritic joints, irrespective of precise diagnosis and disease duration, are enriched with natural regulatory T cells. These results suggest that suppressor cells migrate to and/or multiply at the sites of inflammation as part of the immune responses' effort to combat injurious inflammation.