Inflammatory Arthritic Diseases Research Articles

MyD88 dimerization inhibitor ST2825 targets the aggressiveness of synovial fibroblasts in rheumatoid arthritis patients

BackgroundDimerization of the myeloid differentiation primary response 88 protein (MyD88) plays a pivotal role in the exacerbated response to innate immunity-dependent signaling in rheumatoid arthritis (RA). ST2825 is a highly specific inhibitor of MyD88 dimerization, previously shown to inhibit the pro-inflammatory gene expression in peripheral blood mononuclear cells from RA patients (RA PBMC). In this study, we elucidated the effect of disrupting MyD88 dimerization by ST2825 on the pathological properties of synovial fibroblasts from RA patients (RA SFs).MethodsRA SFs were treated with varying concentrations of ST2825 in the presence or absence of bacterial lipopolysaccharides (LPS) to activate innate immunity-dependent TLR signaling. The DNA content of the RA SFs was quantified by imaging cytometry to investigate the effect of ST2825 on different phases of the cell cycle and apoptosis. RNA-seq was used to assess the global response of the RA SF toward ST2825. The invasiveness of RA SFs in Matrigel matrices was measured in organoid cultures. SFs from osteoarthritis (OA SFs) patients and healthy dermal fibroblasts were used as controls.ResultsST2825 reduced the proliferation of SFs by arresting the cells in the G0/G1 phase of the cell cycle. In support of this finding, transcriptomic analysis by RNA-seq showed that ST2825 may have induced cell cycle arrest by primarily inhibiting the expression of critical cell cycle regulators Cyclin E2 and members of the E2F family transcription factors. Concurrently, ST2825 also downregulated the genes encoding for pain, inflammation, and joint catabolism mediators while upregulating the genes required for the translocation of nuclear proteins into the mitochondria and members of the mitochondrial respiratory complex 1. Finally, we demonstrated that ST2825 inhibited the invasiveness of RA SFs, by showing decreased migration of LPS-treated RA SFs in spheroid cultures.ConclusionsThe pathological properties of the RA SFs, in terms of their aberrant proliferation, increased invasiveness, upregulation of pain and inflammation mediators, and disruption of mitochondrial homeostasis, were attenuated by ST2825 treatment. Taken together with the previously reported anti-inflammatory effects of ST2825 in RA PBMC, this study strongly suggests that targeting MyD88 dimerization could mitigate both systemic and synovial pathologies in a variety of inflammatory arthritic diseases.

Microfluidic-assisted electrospinning, an alternative to coaxial, as a controlled dual drug release system to treat inflammatory arthritic diseases

Inflammatory arthritic diseases are characterized by a persistent inflammation of the synovial tissues where tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) pro-inflammatory cytokines are over-expressed, leading to progressive musculoskeletal disability. Methotrexate (MTX), a disease-modifying-anti-rheumatic drug (DMARD) commonly applied in their treatment, can be used in combination with biological-DMARDs as anti-TNFα antibody to improve the treatments efficacy. However, their systemic administration comes with severe side-effects and limited therapeutic efficacy due to their off-target distribution and short half-life. To overcome such limitations, encapsulation of clinically relevant concentrations of MTX and anti-TNFα antibody into polycaprolactone (PCL) or poly(vinyl-alcohol) (PVA) microfluidic-assisted or coaxial electrospun fibrous meshes is proposed as local controlled dual drug release systems.Release studies show that microfluidic-assisted electrospinning meshes encapsulating both drugs achieved higher concentrations than coaxials. Biological assays using human articular chondrocytes (hACs) and monocytic cells (THP-1 cell line) demonstrate that fibrous meshes encapsulating the drugs are non-toxic. The systems' efficacy is proved by a significant decrease of TNFα and IL-6 concentrations in conditioned medium of lipopolysaccharide (LPS)-stimulated THP-1 cells, especially in the presence of microfluidic-assisted electrospun meshes, when compared with THP-1 conditioned medium (59.5% and 83.9% less, respectively).Therefore, microfluidic-assisted electrospinning fibrous meshes with encapsulating drugs represent an alternative to coaxial, as a local therapy for inflammatory arthritis diseases.

From Science to Success? Targeting Tyrosine Kinase 2 in Spondyloarthritis and Related Chronic Inflammatory Diseases.

Spondyloarthritis (SpA) is a family of inflammatory arthritic diseases, which includes the prototypes of psoriatic arthritis and ankylosing spondylitis. SpA is commonly associated with systemic inflammatory diseases, such as psoriasis and inflammatory bowel disease. Immunological studies, murine models and the genetics of SpA all indicate a pathogenic role for the IL-23/IL-17 axis. Therapeutics targeting the IL-23/IL-17 pathway are successful at providing symptomatic relief, but may not provide complete protection against progression of arthritis. Thus there is still tremendous interest in the discovery of novel therapeutic targets for SpA. Tyrosine kinase 2 (TYK2) is a member of the Janus kinases, which mediate intracellular signaling of cytokines via signal transducer and activator of transcription (STAT) activation. TYK2 plays a crucial role in mediating IL-23 receptor signaling and STAT3 activation. A plethora of natural mutations in and around TYK2 have provided a wealth of data to associate this kinase with autoimmune/autoinflammatory diseases in humans. Induced and natural mutations in murine Tyk2 largely support human data; however, key inter-species differences exist, which means extrapolation of data from murine models to humans needs to be done with caution. Despite these reservations, novel selective TYK2 inhibitors are now proving successful in advanced clinical trials of inflammatory diseases. In this review, we will discuss TYK2 from basic biology to therapeutic targeting, with an emphasis on studies in SpA. Seminal studies uncovering the basic science of TYK2 have provided sound foundations for targeting it in SpA and related inflammatory diseases. TYK2 inhibitors may well be the next blockbuster therapeutic for SpA.

Born to run: The paradox of biomechanical force in spondyloarthritis from an evolutionary perspective.

Spondyloarthritis (SpA) refers to a group of chronic inflammatory arthritic diseases that can be severely debilitating. The most common form of SpA affecting the peripheral skeleton is psoriatic arthritis, while that affecting the axial skeleton is ankylosing spondylitis. SpA has a multifactorial nature, with both genetic and environmental factors initiating and maintaining the disease. Recently, the role of biomechanical stress as an initiator of disease has gained much attention, with efforts focusing on the underlying cellular and molecular mechanisms. In this review, we provide a different view, with emphasis on the apparently contradictory role of physical therapy in SpA owing to the impact of biomechanical stress and put this in an evolutionary context due to changes in environment and lifestyle across time.

Extraction of acetyl 11-keto-β-boswellic acid (AKBA) from Boswellia serrata plant oleo gum resin using novel three phase partitioning (TPP) technique

The oleo gum resin of Boswellia serrata belonging to family Burseraceae, is Ayurvedic medicine and has been used for the treatment of inflammatory diseases and arthritic diseases in many countries. Acetyl 11-keto-β-boswellic acid (AKBA) is a potent anti-inflammatory agent obtained from oleo gum resin of Boswellic serrata. Our aim is to extract maximum amount of AKBA from Boswellic serrata by using Three Phase Partitioning (TPP) technique. In the TPP system, the effect of different process parameters such as ammonium sulfate concentration, extraction time, slurry to t-butanol ratio, solute to t-butanol ratio, pH and temperature, was studied in order to enhance the extraction of AKBA. Under the optimized conditions of ammonium sulfate concentration 0–50% (w/v), extraction time 180min, slurry to t-butanol ratio 1:1 (v/v), solute to solvent ratio 1:25 (w/v), pH 6 and temperature 50°C, the maximum yield of AKBA was found to be (80±0.33mg/g). TPP technique gave higher extraction yield of AKBA compared to conventional Soxhlet extraction (18±0.37mg/g), batch extraction (20±0.45mg/g), ultrasound assisted extraction (UAE) (24.23±0.28mg/g). Thus, TPP can be recommended as an attractive and simple technique for the extraction of AKBA from Boswellic serrata.

Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases

ObjectivesJuvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system....

Prospective outcome analysis of total replacement of the temporomandibular joint with the TMJ Concepts system in patients with inflammatory arthritic diseases

We report the outcomes of patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, who had total replacement of the temporomandibular joint (TMJ) using the TMJ Concepts system between 2005 and 2014. We prospectively measured mouth opening (mm), and pain and dietary function (visual analogue scale (VAS), 1 - 100) before operation, and at 6 weeks, 6 months, one year, and beyond. Forty-six joints were replaced in 26 patients (mean age 40, range 16 - 71), 22 of whom were female. Most had rheumatoid (n=17) or psoriatic arthritis (n=7). At one year the mean (SD) pain scores had fallen from 55 (36) to 2 (7) on the left, and from 62 (31) to 2 (5) on the right (p<0.001). Mean (SD) scores for dietary function had increased from 48(25) to 95(9) (p<0.001), and mouth opening had increased from a mean (SD) of 23(10) mm to 35(5) mm (p<0.001). The joints dislocated during the operation in 5 patients, and 4 had temporary weakness of the facial nerve. Outcomes after replacement of the TMJ with the TMJ Concepts system were good in patients with inflammatory arthritis, which further validates the procedure, as damage to the joint is severe in this group.

Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced arthritis.

IntroductionPathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which, in addition to bone erosion, demonstrates bone formation at the time of clinical manifestations. The objective of this study was to use this model to characterise the histological and molecular changes in bone remodelling, and relate these to the clinical disease development.MethodsA histological and gene expression profiling time-course study on bone remodelling in CIA was linked to onset of clinical symptoms. Global gene expression was studied with a gene chip array system.ResultsThe main histopathological changes in bone structure and inflammation occurred during the first two weeks following the onset of clinical symptoms in the joint. Hereafter, the inflammation declined and remodelling of formed bone dominated.Global gene expression profiling showed simultaneous upregulation of genes related to bone changes and inflammation in week 0 to 2 after onset of clinical disease. Furthermore, we observed time-dependent expression of genes involved in early and late osteoblast differentiation and function, which mirrored the histopathological bone changes. The differentially expressed genes belong to the bone morphogenetic pathway (BMP) and, in addition, include the osteoblast markers integrin-binding sialoprotein (Ibsp), bone gamma-carboxyglutamate protein (Bglap1), and secreted phosphoprotein 1 (Spp1). Pregnancy-associated protein A (Pappa) and periostin (Postn), differentially expressed in the early disease phase, are proposed to participate in bone formation, and we suggest that they play a role in early bone formation in the CIA model. Comparison to human genome-wide association studies (GWAS) revealed differential expression of several genes associated with human arthritis.ConclusionsIn the CIA model, bone formation in the joint starts shortly after onset of clinical symptoms, which results in bony fusion within one to two weeks. This makes it a candidate model for investigating the relationship between inflammation and bone formation in inflammatory arthritis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0531-7) contains supplementary material, which is available to authorized users.

1.57 Prolactin is locally produced in the synovium of patients with inflammatory arthritic diseases and promotes macrophage activation

Background and ObjectivesThe sex hormone prolactin (PRL) has immunomodulatory properties, can be produced by immune cells, and elevated PRL serum levels have been reported in rheumatoid arthritis (RA) patients. Here...

A new cytochrome P450 system from Bacillus megaterium DSM319 for the hydroxylation of 11-keto-β-boswellic acid (KBA)

In the genome of Bacillus megaterium DSM319, a strain who has recently been sequenced to fully exploit its potential for biotechnological purposes, we identified a gene encoding the cytochrome P450 CYP106A1 as well as genes encoding potential redox partners of CYP106A1. We cloned, expressed, and purified CYP106A1 and five potential autologous redox partners, one flavodoxin and four ferredoxins. The flavodoxin and three ferredoxins were able to support the activity of CYP106A1 displaying the first cloned natural redox partners of a cytochrome P450 from B. megaterium. The CYP106A1 system was able to convert the pentacyclic triterpene 11-keto-β-boswellic acid (KBA) belonging to the main bioactive constituents of Boswellia serrata gum resin extracts, which are used to treat inflammatory disorders and arthritic diseases. In order to provide sufficient amounts of the KBA products to characterize them structurally by NMR spectroscopy, recombinant whole-cell biocatalysts were constructed based on B. megaterium MS941. The main product has been identified as 7β-hydroxy-KBA, while the side product (∼20%) was shown to be a mixture of 7β,15α-dihydroxy-KBA and 15α-hydroxy-KBA. Without further optimization 560.7 mg l⁻¹ day⁻¹ of the main product, 7β-hydroxy-KBA, could be obtained thus providing a suitable starting point for the efficient production of modified KBA by chemical tailoring to produce novel KBA derivatives with increased bioavailability and this way more efficient drugs.

Elbow replacement

Elbow replacement or arthroplasty is a good therapeutic option for a large percentage of patients with significant joint destruction. However, many orthopaedic surgeons are not familiar with the surgical approaches or techniques associated with elbow replacement implants. Furthermore, the incidence of complications is higher than in other joint replacements, the most important being infections, mechanical failure, cubital neuropathy, and problems with the triceps. For these reasons, the use of bone arthroplasty in Spain may be less than ideal. Although, inflammatory arthritic diseases, such as rheumatoid arthritis, are the most frequent indication for this operation, distal humerus fractures and post-traumatic disease are a growing indication. This work attempts to summarise the most important current concepts associated with elbow replacement.

Artroplastia de codo

Elbow replacement or arthroplasty is a good therapeutic option for a large percentage of patients with significant joint destruction. However, many orthopaedic surgeons are no familiar with the surgical approaches or techniques associated with elbow replacement implants. Furthermore, the incidence of complications is higher than in other joint replacements, the most important being infections, mechanical failure, cubital neuropathy, and problems with the triceps. For these reasons, the use of bone arthroplasty in Spain may be less than ideal. Although, inflammatory arthritic diseases, such as rheumatoid arthritis, are the most frequent indication for this operation, distal humerus fractures and post-traumatic disease are a growing indication. This work attempts to summarise the most important current concepts associated with elbow replacement.

Pathogenicity of Misfolded and Dimeric HLA-B27 Molecules

The association between HLA-B27 and the group of autoimmune inflammatory arthritic diseases, the spondyloarthropathies (SpAs) which include ankylosing spondylitis (AS) and Reactive Arthritis (ReA), has been well established and remains the strongest association between any HLA molecule and autoimmune disease. The mechanism behind this striking association remains elusive; however animal model and biochemical data suggest that HLA-B27 misfolding may be key to understanding its association with the SpAs. Recent investigations have focused on the unusual biochemical structures of HLA-B27 and their potential role in SpA pathogenesis. Here we discuss how these unusual biochemical structures may participate in cellular events leading to chronic inflammation and thus disease progression.

Patients with inflammatory arthritic diseases harbor elevated serum and synovial fluid levels of free and immune-complexed glucose-6-phosphate isomerase (G6PI)

In K/BxN mice, anti-glucose-6-phosphate isomerase (G6PI) IgG antibodies (Abs) cause joint-specific inflammation and destruction. Anti-G6PI Abs are also present in humans with inflammatory arthritis, especially among patients with rheumatoid arthritis (RA). A contributing factor to the induction of such autoantibodies may be upregulated expression of the corresponding antigen G6PI in affected tissues and/or increased levels of G6PI in the circulation. To determine G6PI levels and the presence of free G6PI and/or G6PI-containing immune complexes in sera and synovial fluids (SF) of patients with different arthritides, serum and SF obtained concomitantly from 91 clinically well-defined arthritis patients were assessed in a blinded manner for G6PI enzymatic assay and for G6PI protein concentration by ELISA. Sera and SF from patients with immune-based inflammatory arthritis contained significantly higher levels of G6PI enzymatic activity compared to sera or SF from patients with non-immune-based inflammatory arthritis or healthy controls. In addition, significantly higher levels of total G6PI protein concentration (including both enzymatically active and inactive forms) were present in sera of RA patients vs. those with other immune-based or non-immune-based inflammatory arthritis.G6PI in sera and SF were present both as G6PI-containing immune complexes and as free G6PI, with the majority of free G6PI existing as tetramers with lesser amounts of dimers and monomers. Levels of G6PI enzymatic activity in the sera of most immune-based inflammatory arthritis patients are elevated and may reflect ongoing inflammation and cell destruction. The high serum levels of enzymatically inactive forms of G6PI in RA relative to those in other arthritic diseases are partially due to G6PI-containing immune complexes, a portion of which also contains C1q. Overall, our study supports the notion that elevated G6PI levels present in patients with immune-based inflammatory arthritis may contribute to elevated levels of anti-G6PI Abs and G6PI/anti-G6PI immune complexes. This, in turn, may trigger production of proinflammatory cytokines and perpetuate the inflammatory process.

Plasma total antioxidant capacity, lipid peroxidation, and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis

Objectives: The metabolism of cells in inflammatory and noninflammatory arthritic joint diseases is subject to complex environmental controls. The aim of the present study was to investigate the total antioxidant capacity (TAC), levels of lipid peroxidation (LPO), and antioxidant enzyme activities in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Design and methods: Plasma levels of TAC, malondialdehyde (MDA), the activities of some erythrocyte antioxidant enzymes, as well as erythrocyte sedimentation rates (ESR) were estimated in patients with RA and OA and compared with controls. Results: The plasma TAC levels were significantly lower in the RA group than the OA and control group ( P < 0.05). Plasma MDA concentrations were significantly higher in patients with RA than those with OA and healthy subjects ( P < 0.05). Erythrocyte GSH-Px and CAT activities were found to be significantly lower in patients with RA than those with OA and healthy subjects ( P < 0.05, P < 0.05, respectively). However, there were no significant differences in erythrocyte SOD activities between the groups ( P > 0.05). ESR were significantly higher in RA patients than in healthy subjects and patients with OA ( P < 0.01). Moreover, there were significant negative correlations between TAC vs. MDA, ESR vs. TAC, and a positive correlation between ESR vs. MDA in the RA group ( r = −0.398, P < 0.05; r = −0.422, P < 0.05; r = 0.530, P < 0.05, respectively). Conclusions: Our results demonstrated that levels of LPO are increased in patients with RA compared to patients with OA. In addition, plasma TAC levels are decreased in RA due to its inflammatory character. We conclude that detecting plasma TAC levels with this novel method may be used as a routine and rapid test to verify the levels of oxidative stress in RA. Furthermore, correlating TAC and LPO levels with acute phase reactants such as ESR may give some clues about disease activity in RA.

Early degradation of type IX and type II collagen with the onset of experimental inflammatory arthritis.

To determine whether following the onset of intraarticular inflammation, there is early damage to articular cartilage, specifically to types II and IX collagen, and the proteoglycan (PG) aggrecan, and whether measurement of the degradation products of these molecules in synovial fluid (SF) and serum may permit the detection of cartilage damage. A rabbit model of rheumatoid arthritis, antigen (ovalbumin)-induced arthritis, was studied. Articular cartilage samples were analyzed by immunoassays for total type II collagen content, its denaturation and cleavage by collagenases, and for type IX collagen content. PG content was determined by colorimetric assay. In serum and SF, total PG content and collagenase-generated peptides of type II collagen were measured. After 6 days, both the PG content and the NC4 domain of type IX collagen were reduced in femoral and tibial cartilage, concomitant with the onset of arthritis. In only the tibial cartilage did this reduction in PG persist up to day 20. However, denatured type II collagen was increased in all cartilage samples, but only on day 20. In SF, the PG content was significantly reduced on day 20, and products of type II collagen cleavage by collagenase were significantly increased on both day 6 and day 20. This study, which is the first of its kind examining changes in both types II and IX collagen and PG content, reveals early damage to both types of collagen as well as to PG in articular cartilage samples following induction of joint inflammation. SF analyses reveal this early damage and may be of value in the study and treatment of inflammatory arthritic diseases such as rheumatoid arthritis.

An anti-inflammatory role for interleukin-11 in established murine collagen-induced arthritis.

Interleukin-11 (IL-11) is a cytokine belonging to the IL-6 family which has both pro- and anti-inflammatory potential. Like IL-6 it can diminish tumour necrosis factor-alpha and IL-1 production, and augment immunoglobulin synthesis. We have explored the immunomodulatory effects of IL-11 treatment in mice in a model of inflammatory autoimmune joint disease, collagen-induced arthritis (CIA). Recombinant human IL-11 was administered at various doses to DBA/1 mice after the onset of CIA. IL-11 treatment caused a significant reduction in the clinical severity of established CIA, which was associated with protection from joint damage, as assessed by histology. Although there was a suggestion at high doses of IL-11 that the anticollagen type II (CII) response may have been augmented, there was no statistically significant effect of IL-11 treatment on anti-CII antibody levels. Similarly, the acute-phase reactant serum amyloid P was only elevated in mice receiving very high doses (50-100 microgram/day) of IL-11. Endogenous IL-11 was abundantly produced in synovial membrane cultures derived from CII-immunized mice with active disease, suggesting that, as in rheumatoid arthritis, this cytokine is spontaneously produced in the inflammatory response in CIA. The results presented here demonstrate an anti-arthritic immunoregulatory role for IL-11 in murine CIA, and suggest that IL-11 is a candidate therapeutic molecule for human inflammatory arthritic diseases.

Prediction of diagnosis in acute and subacute oligoarthritis of unknown origin.

A total of 146 consecutive patients between 18 and 60 yr of age with oligoarthritis of unknown origin (< or = 6 active joints, < or = 8 weeks duration) were examined by a variety of clinical, laboratory and microbiological investigations, and followed longitudinally for 24 weeks. Reactive arthritis was diagnosed in 46 patients (19 induced by Chlamydia trachomatis, 27 by enterobacteria), 62 had undifferentiated arthritis, eight other inflammatory arthritic diseases, 15 acute sarcoid arthritis and 15 non-inflammatory joint diseases. Group differences were found for many baseline variables, but with considerable overlap between the groups. A set of four clinical and laboratory variables (elevated CRP, genitourinary symptoms, metatarsophalangeal joint involvement. HLA B27) could predict reactive arthritis with a sensitivity of 69.2% and a specificity of 93.5%. A wide range of clinical and laboratory examinations are required to determine the final diagnosis in oligoarthritis, but individual and sets of clinical and laboratory measures may give helpful clues for the correct diagnosis.

Total radical-trapping antioxidative capacity of plasma and whole blood chemiluminescence in patients with inflammatory and autoimmune rheumatic diseases.

The total radical-trapping antioxidative capacity (TRAC) of plasma was evaluated in samples from patients suffering from various inflammatory and autoimmune rheumatic diseases (n=104) and correlated with the phorbol ester-stimulated chemiluminescence (CL) of neutrophils and monocytes in unseparated blood. Plasma and blood samples from age- and sex-matched healthy volunteers (n=25) and from patients with non-rheumatic internal diseases (n=31) served as controls. A 2 to 10 fold increase in whole blood chemiluminescence was found in rheumatic patients, which paralleled 50-80% decreased levels of plasma TRAC-values. While significant correlations between CL and TRAC were determined for patients with inflammatory arthritic diseases no correlations were found with patients suffering from connective tissue diseases. Prednisolone treatment of individual patients increased plasma TRAC-values substantially and decreased elevated levels of phagocytic CL generation to that of healthy controls. The main potential application of the assays described here is for the convenient assessment of disease activity and progression in individual patients with rheumatic diseases.

Immunopathogenesis Of Human Inflammatory Arthritis: Lessons From Lyme And Reactive Arthritis

Human inflammatory arthritic diseases developing in response to infections with known pathogens provide unique models for studying the molecular and cellular mechanisms underlying human chronic inflammatory diseases. For example, Lyme disease serves as an appropriate clinical entity for immunopathogenetic studies, since the tickborne spirochete Borrelia burgdorferi, which causes Lyme disease, has been identified [1]. Patients with Lyme disease frequently develop intermittent inflammatory symptoms [2]. In both adults [2] and children [3], most Lyme disease patients will have resolution of their arthritic symptoms over time. However, a subset of patients with Lyme disease (~10*) develop a chronic inflammatory arthritis that resembles other forms of human inflammatory arthritis, including rheumatoid arthritis [4]. Synovial tissue obtained from this subset of patients is histopathologically identical to that of rheumatoid arthritis [2]. T lymphocytes, predominantly CD4~h T cells, are present in the synovial tissue in both arthritides [5]. Similarly, reactive arthritis triggered by Yersinia enterocolitica provides another clinical model for studying the pathogenesis of human inflammatory arthritis. Among the bacteria known to cause reactive arthritis, which include Salmonella, Shigella, Campylobacter, and Chlamydia species, Yersinia is one of the more common etiologic genera [6]. Y. enterocolitica causes acute gastroenteritis. At 1-3 weeks after infection, a subset of patients develop a reactive arthritis that varies from mild arthralgia to severe polyarthritis and usually resolves within a few weeks or months in most patients. Synovial fluid and blood samples from these patients are particularly valuable for pathogenetic studies, since they can be obtained at an early stage of disease from patients with characteristic clinical features, a known time of disease onset, and a serologically and microbiologically confirmed diagnosis. As in Lyme arthritis, a subset of these patients (10*) will