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ID PMID Title PublicationDate abstract
20404456 Immune responses to Epstein-Barr virus in individuals with systemic and organ specific aut 2010 Apr PURPOSE: Autoimmune diseases usually manifest in genetically predisposed individuals following an environmental trigger. There are several viral infections including Epstein-Barr virus (EBV) implicated in the pathogenesis of autoimmune disorders. The aim of this study was to look at the antibody pattern to EBV proteins in the plasma of both systemic and organ specific autoimmune disorders, estimate pro-inflammatory plasma cytokines (IL-8 and TNF-alpha) among these autoimmune patients and compare the observations with those in normal healthy controls. MATERIALS AND METHODS: Samples from 44 rheumatoid arthritis patients, 25 Hashimoto's thyroiditis patients, appropriately age and sex matched healthy controls were tested for EBV IgM antibodies by an immunoblot assay and two cytokines (IL-8 and TNF-alpha) by commercial assays. RESULTS: Among the rheumatoid arthritis patients, 23 (52%) were positive for EBNA1 antibody, while 13 (52%) of the Hashimoto's thyroiditis patients and 12 (30%) of the healthy controls showed similar bands. The intensity of the bands was high in the autoimmune patients when compared to the bands seen in control samples. The difference in the EBNA1 reactivity between rheumatoid arthritis patients and controls were significant (P = 0.038). There was a significant difference in the IgM reactivity to VCAp19 protein between patients and controls (P = 0.011). CONCLUSION: Our study showed an increased EBV activation among the autoimmune patient groups compared to the normal healthy controls. Further studies are required to delineate the association between the aetiology of autoimmune disorders and EBV.
19802716 Interstitial granulomatous dermatitis in rheumatoid arthritis responsive to etanercept. 2010 Jan Interstitial granulomatous dermatitis (IGD) is a rare dermatological condition presenting as erythematous plaques. It may be associated with drug-related adverse reactions and autoimmune diseases. Recent cases of IGD have been reported in rheumatoid arthritis (RA) patients treated with biologic agents. We report a case of RA patient with persistent erythematous plaques who did not respond to traditional disease-modifying anti-rheumatic drugs with a persistent skin condition of erythematous plaque eruptions. A biopsy showed a homogeneous inflammatory infiltrate in the deep dermis composed of large epithelioid histiocytes with occasional granulocytes, leading us to consider a diagnosis of IGD. The cutaneous lesions disappeared after a 3-month treatment with the tumour necrosis factor-alpha (TNF-alpha) inhibitor etanercept. Anti-TNF-alpha agents can antagonise the multiple effects of TNF-alpha on the immune system, effects that are required for the continued maintenance of granulomatous structure, and offer a therapeutic strategy in the treatment of IGD associated with arthritis.
21137220 [Influence of Artrofoon on the current of the metabolic syndrome in patients with rheumato 2010 This article shows observable effects of Artrofoon concerning displays a metabolic syndrome in patients with rheumatoid arthritis. Patients of the basic group received Artrofoon throughout 12 months by 4 tablets a day, thus it was possible to reach authentic decrease in level of uric acid, improvement of indicators of a lipid spectrum of blood, weight reduction, to stabilise arterial pressure. Thus, positive influence of the preparation on the basic displays of a metabolic syndrome has been noted.
18203761 Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumat 2009 Jan BACKGROUND: Tumour necrosis factor alpha blockers in rheumatoid arthritis are known to increase the risk of serious infections defined as life-threatening, requiring hospitalisation or intravenous antibiotics. Recently, new biological agents have become available. Their safety is an important issue. PURPOSE: To assess if biological agents, ie rituximab, abatacept and anakinra increase the risk of serious infections in patients with rheumatoid arthritis in published randomised controlled trials. DATA SOURCE: A systematic review of the literature using PUBMED, EMBASE, Cochrane library and abstracts databases (American College of Rheumatology and European League Against Rheumatism annual meetings) was performed up to October 2007. This search was completed with data from the Food and Drug Administration, the European Agency for the Evaluation of Medicinal Products and manufacturers. DATA EXTRACTION: Three fixed-effect meta-analyses were performed to compare serious infection rates between each biological agent and placebo. Pooled odds ratios (ORs) were calculated, using the Mantel-Haenszel method with a continuity correction. DATA SYNTHESIS: Twelve randomised controlled trials with data concerning serious infections were analysed (three for rituximab, five for abatacept and four for anakinra). They included 745 patients, 1960 patients, 2062 patients and 2112 patients treated by rituximab, abatacept, anakinra and placebo respectively. The overall pooled ORs did not reveal a statistically significant increased risk of serious infection for abatacept and rituximab; this risk was increased for high doses of anakinra (> or =100 mg daily) versus low dose and placebo (ORs = 9.63 (95% CI, 1.31 to 70.91) and 3.40 (95% CI, 1.11 to 10.46) respectively). CONCLUSIONS: These meta-analyses did not reveal a significant increase in the risk of serious infections during rituximab or abatacept treatments in patients with rheumatoid arthritis; however, high doses of anakinra may increase this risk, especially when patients have comorbidity factors. Large studies must be performed to confirm this safety profile in daily practice.
20532967 Changes in apoptotic gene expression in lymphocytes from rheumatoid arthritis and systemic 2010 Sep INTRODUCTION: Systemic lupus erythematosus (SLE) and rheumatoid arthritis have complex genetic traits, but in both autoimmune diseases, dysfunctional apoptosis appears to play a part in disease pathology. This study examined the levels of in vitro apoptosis in lymphocytes from healthy, rheumatoid arthritis (RA) and SLE individuals and related observed differences to their lymphocyte apoptosis gene profiles. MATERIALS AND METHODS: Lymphocytes were assessed for cell death by nuclear pyknosis and DNA fragmentation. Control, SLE and RA apoptosis gene profiles were obtained by quantitative real-time polymerase chain reaction (QRT-PCR) analysis. RESULTS AND DISCUSSION: The mean levels of pyknosis in RA and SLE freshly isolated lymphocytes were significantly higher than in control lymphocytes. Ninety-three apoptosis genes were analysed by QRT-PCR of mRNA from RA, SLE and healthy lymphocytes. We identified significant differences (p < 0.05) in the expression of the same 11 of 93 and two of 93 apoptotic genes in individual SLE and RA patients tested as compared with controls. CONCLUSION: We propose that similarly altered expression of specific apoptotic regulatory genes (e.g., the death effector domain-containing DNA-binding protein and apoptosis-associated speck-like protein containing a CARD) occurs in the lymphocytes of individual patients with SLE or RA that may influence the extent and rate of spontaneous apoptosis in these autoimmune conditions.
21047805 Cytokine pattern in very early rheumatoid arthritis favours B-cell activation and survival 2011 Feb OBJECTIVES: B cells play an important role in the perpetuation of RA, particularly as autoantibody-producing cells. The ICs that further develop deposit in the joints and aggravate the inflammatory process. However, B-cell contribution in the very early stage of the disease remains unknown. The main goal of this work was to determine the concentration of cytokines potentially relevant for B-cell activation in serum from very early polyarthritis patients, with <6 weeks of disease duration, who latter on evolved into very early RA (VERA). METHODS: A proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF) and IL-21 levels were measured by ELISA in the serum of VERA, other very early arthritis (VEA), established RA patients and controls. SF samples of established RA were also analysed. RESULTS: VERA patients have higher levels of APRIL and BAFF as compared with VEA, established RA and controls. Furthermore, APRIL and BAFF levels are also significantly elevated in RA-SF when compared with serum. CONCLUSIONS: The increased levels of APRIL and BAFF in VERA patients suggests that B-cell activation and the development of autoreactive B-cell responses might be crucial in early phases of RA. Therefore, APRIL and BAFF could be promising targets for therapy in the early phase of RA.
19644884 Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug effic 2009 Aug OBJECTIVE: To assess the catabolism of methotrexate (MTX) to 7-hydroxy-MTX (7-OH-MTX) in patients with rheumatoid arthritis as well as the effect of folic acid and folinic acid on this catabolism. METHODS: Urinary excretion of MTX and its catabolite, 7-OH-MTX, was measured in 2 24-hour urine specimens collected after MTX therapy. Urine samples were collected from patients after the sixth and seventh weekly doses of MTX. MTX and 7-OH-MTX concentrations were determined by high-performance liquid chromatography mass spectrometry. Swelling and pain/tenderness indices were used to measure symptoms before and at 6 and 7 weeks of therapy. Patients received either folic acid or folinic acid supplements (1 mg/day) from week 6 to week 7. RESULTS: Folic acid inhibited aldehyde oxidase (AO), the enzyme that produces 7-OH-MTX, but folinic acid did not. Excretion of 7-OH-MTX (determined as a percentage of the dose of MTX or as mg 7-OH-MTX/gm creatinine) was not normally distributed (n=39). Patients with marked improvement in swelling and pain/tenderness indices had a lower mean 7-OH-MTX excretion level (P<0.05). Patients who received folic acid supplements had decreased 7-OH-MTX excretion (P=0.03). Relatively high 7-OH-MTX excretion was correlated with relatively high MTX excretion and with relatively low MTX retention in vivo (P<0.05) (n=35). CONCLUSION: Our findings of a non-normal distribution of 7-OH-MTX excretion suggest that there are at least 2 phenotypes for this catabolism. Decreased 7-OH-MTX formation suggests folic acid inhibition of AO and a better clinical response, while increased 7-OH-MTX formation may interfere with MTX polyglutamylation and binding to enzymes and, therefore, may increase MTX excretion and decrease MTX retention and efficacy in vivo.
20381398 Complications following radiosynoviorthesis in osteoarthritis and arthroplasty: osteonecro 2010 May OBJECTIVES: In the literature, radiosynoviorthesis (RSO) has been associated only with a small number of complications. There is a trend towards increasing the use of RSO in diverse indications. After repeatedly observing several complications following RSO, a retrospective evaluation was undertaken to estimate the safety of this method. METHODS: Between 1995-2007, we evaluated the outcome of RSO in 93 patients (143 knees, seven hips, seven shoulders, three elbows, one ankle) who presented to our orthopaedic department after joint treatment with yttrium-90((90)Y) or Rhenium-186((186)Re) colloid in an external nuclear medicine institution. RESULTS: Seventy-nine of the 93 RSO treated patients had advanced primary or secondary osteoarthritis (OA), 12 had an arthroplasty. In seven cases, rheumatoid arthritis (RA) was responsible for secondary OA. The benefit in pain relief, as self-reported by the patients was low. Twenty-two of the 93 patients showed complications following RSO. We observed osteonecrosis (ON) in 19 and infection in five patients, including two with both complications. These findings were proven clinically, radiologically, intraoperatively, microbiologically and histologically. Statistical analysis revealed a strong correlation of arthroplasty to infection (rho=0.798, alpha=0.01), and a strong correlation of chronic obstructive pulmonary disease (COPD) and RA to ON following RSO (rho=0.674, alpha=0.01). Diabetes mellitus (DM) was also significantly correlated to ON after RSO treatment (rho=0.488,alpha=0.05). CONCLUSIONS: Our data suggest that RSO may not be as safe as it has previously been reported, especially in advanced OA and arthroplasty.
20192996 The role of antibodies in inflammatory arthritis. 2010 Jan Inflammatory arthritis presents in a variety of diseases, from rheumatoid arthritis to hepatitis. Antibodies to autoantigens or to microbial constituents are commonly associated with these conditions. In some cases, the antibodies have diagnostic and prognostic relevance. It cannot as yet be determined definitively that any of them mediate joint damage, although the evidence from animal models indicates that this mechanism is likely. The purpose of this article is to give an overview of the spectrum of antibodies found in a variety of inflammatory arthritides. The relevant animal models are also discussed.
19359261 Association of methotrexate and tumour necrosis factor antagonists with risk of infectious 2010 Feb OBJECTIVE: To examine the association of methotrexate (MTX) and tumour necrosis factor (TNF) antagonists with the risk of infectious outcomes including opportunistic infections in patients with rheumatoid arthritis (RA). METHODS: Patients with RA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry prescribed MTX, TNF antagonists or other disease-modifying antirheumatic drugs (DMARDs) were included. The primary outcomes were incident overall and opportunistic infections. Incident rate ratios were calculated using generalised estimating equation Poisson regression models adjusted for demographics, comorbidities and RA disease activity measures. RESULTS: A total of 7971 patients with RA were followed. The adjusted rate of infections per 100 person-years was increased among users of MTX (30.9, 95% CI 29.2 to 32.7), TNF antagonists (40.1, 95% CI 37.0 to 43.4) and a combination of MTX and TNF antagonists (37.1, 95% CI 34.9 to 39.3) compared with users of other non-biological DMARDs (24.5, 95% CI 21.8 to 27.5). The adjusted incidence rate ratio (IRR) was increased in patients treated with MTX (IRR 1.30, 95% CI 1.12 to 1.50) and TNF antagonists (IRR 1.52, 95% CI 1.30 to 1.78) compared with those treated with other DMARDs. TNF antagonist use was associated with an increased risk of opportunistic infections (IRR 1.67, 95% CI 0.95 to 2.94). Prednisone use was associated with an increased risk of opportunistic infections (IRR 1.63, 95% CI 1.20 to 2.21) and an increased risk of overall infection at doses >10 mg daily (IRR 1.30, 95% CI 1.11 to 1.53). CONCLUSIONS: MTX, TNF antagonists and prednisone at doses >10 mg daily were associated with increased risks of overall infections. Low-dose prednisone and TNF antagonists (but not MTX) increased the risk of opportunistic infections.
20862478 [How do T-cells become activated in joints?]. 2010 Oct Activated CD4+ T-cells are found in joints of patients with rheumatoid arthritis and are involved in the joint destroying autoimmune response. Besides proinflammatory cytokine production T-cells are indispensable for the activation of B-cells, the so-called T-cell help for B-cells. However, the recognition of autoantigens by T-cells seems of utmost importance for the pathogenesis of rheumatoid arthritis. Selective inhibition of this process is therefore one of the most interesting therapeutic targets for the future.
19435720 FoxO3a involved in neutrophil and T cell survival is overexpressed in rheumatoid blood and 2010 Apr OBJECTIVE: FoxO3a is a transcriptional factor implicated in cell cycle regulation and apoptosis. Since rheumatoid arthritis (RA) is associated with apoptosis defects, the expression level, regulation and phosphorylation status of FoxO3a was investigated in blood and synovium from patients with RA. METHODS: In microarray experiments, an overexpression of FoxO3a mRNA was observed in blood from patients with RA compared with healthy controls. FoxO3a mRNA expression was quantified in polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells from patients with RA by qRT-PCR. Total FoxO3a and phosphorylated FoxO3a (pFoxO3a) protein expression was analysed in blood leucocytes from patients with RA versus controls and in synovium from patients with RA versus patients with osteoarthritis (OA) by immunostaining. RESULTS: FoxO3a mRNA and protein expression levels were increased in blood from patients with RA compared with controls. FoxO3a overexpression was primarily observed in PMNs. In synovium from patients with RA, both total and inactive phosphorylated FoxO3a proteins were detected. FoxO3a was detected primarily in the sublining T lymphocytes of synovium from patients with RA compared with the lining layer tissue from patients with RA and OA, underlying a role for FoxO3a proteins in inflammation in RA. CONCLUSION: The overexpression of FoxO3a in blood from patients with RA, particularly in PMNs, suggests a potential role for this gene in the pathogenesis of RA through increased survival of blood PMNs. In synovium from patients with RA, FoxO3a mainly detected in inflammatory aggregates may also regulate the chronic survival of T lymphocytes.
19565507 Anti-cyclic citrullinated peptide antibodies from rheumatoid arthritis patients activate c 2009 Jul OBJECTIVE: It has been suggested that anti-citrullinated protein antibodies (ACPAs) play an important role in the pathogenesis of rheumatoid arthritis (RA). To exert their pathologic effects, ACPAs must recruit immune effector mechanisms such as activation of the complement system. Mouse models of RA have shown that, surprisingly, arthritogenic antibodies activate the alternative pathway of complement rather than the expected classical pathway. This study was undertaken to investigate whether human anti-cyclic citrullinated peptide (anti-CCP) antibodies activate the complement system in vitro and, if so, which pathways of complement activation are used. METHODS: We set up novel assays to analyze complement activation by anti-CCP antibodies, using cyclic citrullinated peptide-coated plates, specific buffers, and normal and complement-deficient sera as a source of complement. RESULTS: Anti-CCP antibodies activated complement in a dose-dependent manner via the classical pathway of complement, and, surprisingly, via the alternative pathway of complement. The lectin pathway was not activated by anti-CCP antibodies. Complement activation proceeded in vitro up to the formation of the membrane attack complex, indicating that all activation steps, including the release of C5a, took place. CONCLUSION: Our findings indicate that anti-CCP antibodies activate the complement system in vitro via the classical and alternative pathways but not via the lectin pathway. These findings are relevant for the design of interventions aimed at inhibition of complement-mediated damage in RA.
19116907 Association of the TRAF1/C5 locus with increased mortality, particularly from malignancy o 2009 Jan OBJECTIVE: Recent genome-wide association studies have identified TRAF1/C5 as a rheumatoid arthritis (RA) susceptibility locus. Tumor necrosis factor receptor-associated factor 1 (TRAF1) has been implicated in the regulation of antiapoptotic pathways, whereas C5 has a well-established role in defense against infection. The purpose of this study was to examine the association of the TRAF1/C5 locus with death in patients with RA. METHODS: Genomic DNA samples were collected from a prospective cohort of 400 RA patients. TRAF1/C5 rs3761847 was identified using real-time polymerase chain reaction and melting curve analyses. The association of TRAF1/C5 rs3761847 alleles with the risk of death was assessed using Cox proportional hazards regression analyses. RESULTS: TRAF1/C5 rs3761847 GG homozygote status was associated with an increased risk of death (hazard ratio 3.96 [95% confidence interval 1.24-12.6], P=0.020) as compared with AA homozygote status. The excess mortality was attributed to deaths due to malignancies and sepsis but not cardiovascular disease (CVD). This polymorphism was one of the strongest predictors of death in RA (for TRAF1/C5 GG versus AA, hazard ratio 3.85 [95% confidence interval 1.18-12.59], P=0.026) alongside the erythrocyte sedimentation rate, triglyceride level, prednisolone use, and age. CONCLUSION: The risk of death in RA is increased in TRAF1/C5 rs3761847 GG homozygotes and appears to be independent of RA activity and severity as well as comorbidities relevant to CVD. If this finding is replicated in future studies, TRAF1/C5 genotyping could identify patients at increased risk of death, particularly death due to malignancy or sepsis.
19249228 Total alkaloids from Radix Linderae prevent the production of inflammatory mediators in li 2009 Apr Radix Linderae, the dry roots of Lindera aggregata (Sims) Kosterm (L. strychnifolia Vill), has been long-term used in traditional Chinese medicine for treating various diseases, and alkaloids are believed to be the main active components. Previously, we reported that the total alkaloids from Radix Linderae (TARL) could effectively alleviate inflammation and protect joints from destruction in mouse collagen-induced arthritis, an animal model of human rheumatoid arthritis (RA). To get insight into the underlying mechanisms of TARL, the present study was performed to investigate the effects of TARL on the activation of macrophages and resultant production of inflammatory mediators. In vitro, TARL concentration-dependently prevented the production of nitric oxide, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well as the expressions of iNOS, IL-1beta and TNF-alpha mRNA in RAW 264.7 cells stimulated by lipopolysaccharide (LPS). However, it showed little effect on the production of interleukin-6 (IL-6) and the expression of IL-6 mRNA. Signal transduction studies showed that TARL significantly down-regulated the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase rather than c-jun NH(2)-terminal kinase (JNK). Additionally, TARL prominently decreased LPS-induced activation of IKKalpha and phosphorylation of p65 on serine 276, but had little impact on the phosphorylation and degradation of IkappaBalpha. In summary, our results demonstrate that TARL exhibits inhibitory effects on the production of inflammatory mediators from macrophages via blocking NF-kappaB and MAPKs signaling pathways. The findings provide a plausible explanation for the therapeutic efficiency of TARL on the inflammation and joint destruction in RA.
19760078 Causes of death in patients with rheumatoid arthritis from 1971 to 1991 with special refer 2009 Dec Rheumatoid arthritis (RA) patients have premature mortality, mostly attributed to cardiovascular diseases (CVDs). We studied causes of death (CoDs) and contribution of autopsy to them in RA patients treated at a single hospital responsible for primary to tertiary RA treatment in Helsinki. In 1971-1991, 960 RA patients died. The leading CoDs were CVDs, RA, and infections. Over 1971-1991, RA and renal deaths declined, but other CoDs showed no change. Autopsied patients died more frequently than nonautopsied of coronary heart disease (CHD) and gastrointestinal disorders, but less frequently of RA, renal, and endocrinologic diseases. Our finding of autopsied patients having CHD more frequently as a CoD may indicate that CHD, which may be asymptomatic in RA, may be overlooked during lifetime.
22736316 A subcutaneous tumour in a patient with rheumatoid arthritis. 2010 Apr 22 A 79-year-old Caucasian woman with rheumatoid arthritis (RA) for 27 years presented with a swelling on her left wrist. Both pain and a tingling sensation in the radial four fingers could be elicited by applying light pressure on the swelling. The patient was uncertain as to the actual onset of this swelling and had not complained, as it resembled many of the swellings of the hand region she had previously experienced. Primarily, an organised tenosynovitis was suspected with a presumed pressure on the median nerve, and a puncture was considered. Ultrasonography diagnosed a large hypoechoic mass. This is not unusual with longstanding inflammatory changes, which may contain elements of connective tissue. Using the Doppler function it turned out to be highly vascularised. The tumour could not be removed, but histology revealed a diagnosis of schwannoma.
20398022 Insulin resistance in rheumatoid arthritis: the impact of the anti-TNF-alpha therapy. 2010 Apr Increased prevalence of insulin resistance has been observed in patients with rheumatoid arthritis (RA). High-grade systemic inflammation is implicated in the development of insulin resistance in these patients. Tumor necrosis factor (TNF)-alpha is a potent proinflammatory cytokine that plays a role in the initiation and progression of inflammation and the mechanisms associated with accelerated atherosclerosis in RA. In assessing data immediately prior to and after intravenous infusion of the anti-TNF-alpha monoclonal antibody-infliximab in RA patients on period treatment with this drug attributable to disease refractory to conventional disease-modifying antirheumatic drugs, a dramatic improvement of insulin resistance and insulin sensitivity was observed. A long-term positive effect of TNF-alpha antagonists infliximab and etanercept on insulin resistance in RA patients with severe disease was also reported. These results highlight the importance of therapies that act blocking TNF-alpha function to reduce the mechanisms implicated in the development of the metabolic syndrome observed in RA.
20359615 [Interstitial lung disease and anti-TNF-alpha therapy in rheumatoid arthritis: Two differe 2010 Mar The first lung complications of anti-TNF-alpha therapy in rheumatoid arthritis (RA) that were reported were infections. Recently, interstitial lung disease (ILD) has been described as a consequence of this treatment. We report two cases of women treated with anti-TNF-alpha therapy for RA who both developed exacerbations of their preexisting ILD thought to be due to the treatment. In one case, this complication occurred 2 months after anti-TNF-alpha therapy, whereas the delay of occurrence was 26 months in the second case. Based on these two cases and on the first 40 observations in the literature, we hypothesize that ILD may be exacerbated according to two distinct patterns during anti-TNF-alpha treatment for RA, occurring early (most frequently) or late after treatment was started, with a mean of 4 and 26 months, respectively. Other features that may differ between these two presentations include the risk factors, the anti-TNF-alpha molecule used, the histopathological pattern, and the prognosis.
18608178 Cell surface and relative mRNA expression of heat shock protein 70 in human synovial cells 2009 Jan Heat shock proteins (Hsps) have been repeatedly implicated to participate in the pathogenesis of rheumatoid arthritis (RA). METHODS: Herein, Hsp70 cell surface and mRNA expression were studied in human fibroblast-like synovial cells, dermal fibroblasts and peripheral blood leukocytes derived from 24 RA patients, who underwent synovectomy by using flow-cytometric analysis and real-time quantitative reverse-transcriptase polymerase chain reaction. For comparison, peripheral blood leukocytes of 17 healthy controls were tested. RESULTS: Significantly higher Hsp70 membrane positivity was found on fibroblast-like synovial cells in RA patients (average 18.3%, median 16.5%) than on autologous and healthy control peripheral blood lymphocytes (RA patients: average 4.7%, median 2.9%, p = 0.002; healthy controls: average 6.0%, median 4.5%, p = 0.002) and/or autologous dermal fibroblasts (average 5.1%, median 4.3%, p < 0.001). Strong Hsp70 cell surface expression was also found on peripheral blood monocytes of RA patients (average 53.0%, median 58.1%) and healthy controls (average 49.4%, median 47.5%, p = 0.52). Peripheral blood granulocytes of healthy controls (average 41.8%, median 41.4%) showed significantly increased Hsp70 expression comparing with RA patients (average 10.7%, median 6.4%, p = 0.005). Significantly higher Hsp70 gene expression was observed in synovial cells of RA patients (average 2.04, median 1.7) when compared with autologous peripheral blood leukocytes (average 0.75, median 0.68; p < 0.001). However, the difference in Hsp70 gene expression between RA-derived synovial cells and healthy control peripheral blood leukocytes (average 1.69, median 1.64) was not observed (p = 0.83). We also found significantly lower relative gene expression in peripheral blood leukocytes of RA patients in comparison with healthy controls (p < 0.001). Interestingly, we found that Hsp70 gene expression in RA non-affected skin dermis gained from the operation wound was 3.7-fold higher in average (average 7.6, median 8.3) when compared to autologous RA-affected synovial tissue (p < 0.001); 10.1-fold higher in average when compared to autologous peripheral blood leukocytes (p < 0.001) and 4.5-fold higher in average comparing to control peripheral blood leukocytes (p < 0.001). CONCLUSION: Hsp70 gene expression in RA-affected synovial tissue is followed by Hsp70 cell surface expression on fibroblast-like synovial cells growing from RA synovial tissue. Hsp70 may be translocated to the cell surface from the cytosol and/or Hsp70 released from inflamed synovial tissue may be captured onto the membrane of synovial cells from the extracellular space via Hsp receptors. As a physiological response to potentially harmful enviromental stress factors, skin dermis produces higher levels of Hsp70 comparing to the cells of internal organs and tissues.