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ID PMID Title PublicationDate abstract
17134042 Atlantoaxial instability secondary to rheumatoid arthritis. 2006 Nov Multiple elements contribute to the stability of the anterior C1-C2 articulation, making this region subject to pathologies including trauma, inflammation, infection, and congenital deformities. C1-C2 instability places a patient at risk for significant neurologic compromise. Radiologic imaging plays a fundamental role in diagnosing atlantoaxial instability, indicating etiology, showing details of associated abnormalities, and providing information for planning treatment.
16751154 Anakinra (interleukin-1 receptor antagonist) has positive effects on function and quality 2006 Mar Rheumatoid arthritis (RA) has severe and lasting effects on quality of life. This review (1) describes the disease progression, disability, and joint destruction that seriously alter a patient's quality of life, and (2) explains how the interleukin-1 receptor antagonist (IL-1Ra), anakinra, retards the progress of disease, thereby improving outcomes. Relevant articles were reviewed with a focus on RA, anakinra, and functional and quality-of-life outcomes. In randomized, controlled trials, the IL-1Ra anakinra provided meaningful benefits for patients with active RA, such as decreased signs and symptoms of disease, slower radiographic disease progression, reduced disability, and improved health-related quality of life. The biologic agent, anakinra, provides to patients with RA a valuable treatment option that has a positive impact on both function and quality of life.
17911391 Diamonds are forever: the cortisone legacy. 2007 Oct The year 1946 was not only the year that the Society for Endocrinology was founded, but also the year that Edward Kendall's compound E (cortisone) was first synthesised by Louis Sarett. By 1948, sufficient quantities of compound E were available for the rheumatologist Philip Hench to test it successfully for the first time in a patient with rheumatoid arthritis. It was immediately hailed as a 'wonder drug' and was shown to be effective in a number of inflammation-associated conditions, most notably rheumatoid arthritis. The subsequent development of endocrinology as a discipline is inextricably linked to the chemistry, biology and medicine of antiinflammatory glucocorticoids. Sixty years after the first chemical synthesis of cortisone, corticosteroids remain among the top ten most commonly used prescription and over the counter drugs. Basic and clinical studies of glucocorticoid biosynthesis, metabolism and action have trail-blazed developments in endocrinology ever since. This article surveys the extraordinary cortisone timeline, from first synthesis until now. The concluding scientific message is that intracrine metabolism of cortisone to cortisol via 11beta hydroxysteroid dehydrogenase type 1 likely sustains local amplification of glucocorticoid action at sites of inflammation throughout the body. The broader message is that the discovery of compound E by Kendall (basic scientist), its large-scale synthesis by Sarett (industrial chemist) and its therapeutic application by Hench (rheumatologist) serves as a paradigm for modern translational medicine. It is concluded that endocrinology will remain a force in health and disease if it continues to evolve sans frontières at the basic/applied/clinical science interface. A challenge for the Society for Endocrinology is to ensure this happens.
17209660 Inhibiting costimulatory activation of T cells : a viable treatment option for rheumatoid 2007 There is now good evidence that T cells play a central role in the inflammatory pathway that leads to the persistent synovitis that causes joint damage in rheumatoid arthritis (RA). T cells require two signals to become activated. The second step in the activation of T cells involves costimulatory pathways, the best described pathway being the binding of CD28 on T cells to CD80/86 on antigen-presenting cells. This observation has led to the development of a new category of biological response modifier. Abatacept is a fusion protein (cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin [CTLA4Ig]); which blocks the binding of CD28 by avidly binding CD80/86. Without this costimulatory activation, the T cell becomes anergic. Abatacept has consistently been shown to improve the signs and symptoms of RA in phase II and phase III trials in patients with an inadequate response to methotrexate and anti-tumour necrosis factor (TNF) therapy. Onset of action is rapid and efficacy is maintained during the period of treatment. Recent trials have also provided evidence of improvement in quality-of-life measures and radiographic progression. The safety profile to date has also been favourable and supports the theory that targeting naive T cells early in the inflammatory pathway will lead to immunomodulation rather than immunosuppression. The evidence produced so far suggests that abatacept will be a useful addition to the available therapies for patients with RA.
17981742 The role of chemokines in leucocyte-stromal interactions in rheumatoid arthritis. 2008 Jan 1 New dimensions in our understanding of immune cell trafficking in health and disease have been opened by the discovery of chemokines and their receptors. This family of chemo-attractant cytokines performs essential roles in the recruitment and subsequent positioning of leucocyte subsets within tissue microenvironments. Investigation of chemokine networks offers a novel approach to understand the mechanisms by which inflammatory cells persist in diseases such as rheumatoid arthritis (RA), where evidence is mounting that the inappropriate temporal and spatial expression of chemokines and/or their receptors may impair the resolution of leucocyte infiltrates. The recognition that stromal cells such as fibroblasts, as active components of tissue specific microenvironments, are able to determine the type and persistence of inflammatory infiltrates has opened new vistas in research. Stromal cells are active contributors to cytokine and inflammatory chemokine networks which result in immune cell recruitment and activation. However an intriguing role of stromal cells has been demonstrated in the inappropriate expression of constitutive, housekeeping chemokines, which contribute to the persistence of inflammation by actively blocking its resolution.
17202338 Klotho--a common link in physiological and rheumatoid arthritis-related aging of human CD4 2007 Jan 15 Human CD4(+) T lymphocytes undergo aging-related changes leading to decreased immunity to infections and neoplasms, and to increased frequency of autoimmune diseases including rheumatoid arthritis (RA). Certain changes, observed in the CD4(+) cells of RA patients, resemble those observed during physiological aging, but occur at earlier age. Underlying cellular mechanism(s) of these similarities are so far largely unknown. Here we show that KLOTHO, a beta-glucuronidase gene whose activity changes are associated with aging phenotype, is down-regulated at the mRNA, protein, and enzymatic (beta-glucuronidase) activity levels both in the healthy elderly and especially in RA CD4(+) lymphocytes. Although the exact role of Klotho activity for CD4(+) cell function is unknown, we propose here that it might be involved in anti-inflammatory processes occurring in the young and healthy individuals, but reduced in both healthy elderly and RA patients. To support this hypothesis, we show here that the reduction of Klotho expression and activity in both elderly and patients' lymphocytes occurs in concert with the down-regulation of T cell costimulatory molecule CD28, the latter known to be dependent on increased levels of TNF-alpha. Thus, a common mechanism of KLOTHO down-regulation, but executed at various times in life, may underlie both physiological and disease-related T cell aging. Klotho activity might become a target of anti-RA drug development as well as a tool to help increase the immune system efficiency in the elderly.
17684931 [Role of tumor necrosis factor family ligands in the pathogenesis of rheumatoid arthritis- 2007 Apr Receptor activator of nuclear factor XB ligand (RANKL) belongs to the TNF superfamily of cytokines. It plays a key role in osteoclastogenesis, activation, and survival of osteoclasts. The differentiation of macrophage/monocyte-like cells into osteoclasts critically depends on the binding of monocyte-colony stimulating factor (M-CSF) and RANKL by their respective plasma-membrane receptors, c-Fms and RANK. Osteoprotegerin (OPG), a soluble protein of the TNF receptor superfamily that is synthesized mainly by osteoblasts, is a decoy receptor that binds RANKL. In this way OPG competes with RANK what results in the inhibition of osteoclastogenesis and bone resorption. It has been shown that the RANKL/OPG ratio may determine the delicate balance between bone resorption and synthesis. Under normal conditions RANKL is mainly produced by osteoblasts and bone marrow stromal cells. However, in many pathological conditions such as rheumatoid arthritis (RA) and neoplastic osteolysis RANKL is also produced by T and B lymphocytes, macrophages/ monocytes, fibroblasts, synoviocytes, and megakaryocytes. In RA osteolysis is promoted not only by M-CSF and RANKL, but also by other cytokines (TNF, IL-1beta, IL-6, IL-7, IL-11, IL-15, IL-17, IL-18), hormones (PTH, PTH-rP, corticosteroids), and prostaglandin E2. On the contrary, OPG, interferon gamma, IL-4, TGF-beta, bifosfonians, and estrogens inhibit RA-associated osteoclastogenesis. Recently, therapeutics for pathological bone destruction targeting RANKL pathways have been used for the treatment of postmenopausal osteoporosis.
17216021 [Study of vitamin D status of rheumatoid arthritis patients. Rationale and design of a cro 2006 Oct The fundamental role of Vitamin D has been long known in regulating calcium homeostasis and bone metabolism. An increased contribution of Vitamin D was recently described in association with a lower incidence of Rheumatoid Arthritis (RA). This must not be surprising, as the immunomodulating effects of Vitamin D are clear, which have been attributed protective effects in autoimmune disorders such as some chronic inflammatory bowel diseases, multiple sclerosis and type I diabetes. An interaction was suggested between Vitamin D metabolism and inflammation indexes through mediation of TNF-alpha which is also especially involved in osteoclastic resorption and therefore in bone loss processes. Some preliminary data would indicate an association between seasonal changes of Vitamin D serum levels, latitude and disease activity (DAS28) in RA patients. Consequently, the Osteoporosis and Metabolic Bone Diseases Study Group of SIR believes that there are grounded reasons for assessing the Vitamin D status of RA patients in order to investigate whether this is to be related to physiopathological and clinical aspects of disease other than those of bone involvement. Primary end point of the study will be to assess the levels of 25 OH Vitamin D in RA patients. Secondary endpoints will include correlation with dis-ease activity, densitometry values and bone turnover. The cross-sectional study will enroll patients of both sex genders, age ranging between 30 and 75 years according to the 1988 ACR criteria, onset of symptoms at least 2 years prior to study enrollment. Patients will be excluded suffering from osteo-metabolic diseases, liver and kidney insufficiency and those administered Vitamin D boli in the previous 12 months. Disease activity will be evaluated with the HAQ. Hemato-chemical tests and femoral and lumbar bone densitometry will be performed, unless recently undergone by patients. Blood levels of 25 OH C Vitamin D and PHT and of the two bone remodelling markers (bone alkaline phosphatase and serum CTX) will be measured, as well. Patient enrollment will start on February 2007 and will last 4 months. By the end of 2007 the study will be concluded and results will be published.
19024273 [Treatment strategy for rheumatoid arthritis in Croatia]. 2008 The main objectives of the current treatment of rheumatoid arthritis are disease control, inhibition of radiographic progression and finally remission. Presumptions to achieving these goals are early diagnosis of rheumatoid arthritis and early administered therapy with disease modifying drugs as monotherapy or combination of drugs. The optimal therapeutic response is influenced by tight control of the patients, evaluation of efficacy and tolerability and change of therapeutic strategy as needed. For the patients refractory to standard disease modifying drugs anti-TNFa drugs can be added. The choice of anti-TNFalpha drug should be done regarding efficacy, tolerability and method of drug administration. In a patient who is failing to respond after 3 months to one anti-TNFalpha we can try other one or rituximab.
17298211 Advanced glycation end-product pentosidine is not a relevant marker of disease activity in 2007 Advanced glycation end-product (AGE) pentosidine has previously been demonstrated in different tissues and body fluids. It was suggested as a novel marker for evaluating the pathologic activity in rheumatoid arthritis (RA). In this study we analyzed the relation between pentosidine and markers of inflammation, cartilage turnover, immune response, and disease status of RA. Using HPLC, we analyzed pentosidine in serum and synovial fluid from 39 patients with RA and in serum from 38 healthy controls. Cartilage oligomeric matrix protein (COMP) and antibodies to CCP (anti-CCP) were measured by ELISA. Clinical disease status was assessed by Disease Activity Score 28 (DAS 28) and functional status by Health Assessment Questionnaire (HAQ). We demonstrated significantly higher serum levels of pentosidine in RA patients in comparison with controls. Pentosidine in serum significantly correlated with pentosidine in synovial fluid. Serum pentosidine levels were associated with erythrocyte sedimentation rate (p<0.03) but not with CRP, COMP, anti-CCP antibodies, DAS 28, or HAQ. In contrast to previous studies, we could not show any correlation of pentosidine levels with inflammatory status, clinical disease activity, markers of immune response, or cartilage breakdown. However, AGEs can be suggested as important players participating in joint destruction rather than markers of disease activity.
16845709 Indications for lowering LDL cholesterol in rheumatoid arthritis: an unrecognized problem. 2006 Sep OBJECTIVE: To evaluate the prevalence of patients with rheumatoid arthritis (RA) in whom lowering low density lipoprotein cholesterol (LDL-C) should be considered in accord with the ATPIII guidelines. The treatment goals are based on the number of risk factors (RF) other than LDL-C. The goal for 0-1 RF is < 160 mg/l, for multiple RF < 130 mg/l, and < 100 mg/l for coronary heart disease (CHD) or CHD risk equivalent (other clinical atherosclerotic diseases and diabetes mellitus). METHODS: A cross-sectional study was conducted in 145 patients with RA. We recorded the patients' characteristics, the potential risk factors for CHD, and results of lipid profile tests [total cholesterol (TC), high density lipoprotein cholesterol, and LDL-C]. RESULTS: Of the 145 patients recruited, 23 had LDL-C lowering therapy. Of the remaining 122 patients (mean age 54 +/- 15 years), of whom 101 (83%) were women, 109 were taking a disease modifying antirheumatic drug. At the time of the study, disease duration was 12 +/- 10 years. Twenty-seven (22%) of the 122 patients needed lowering of LDL-C. If RA was considered as an additional risk factor or a major risk factor, like diabetes mellitus, 35 patients (29%) and 86 (70%) patients, respectively, needed lowering therapy. CONCLUSION: Our study shows the high percentage of patients with RA for whom LDL-C intervention should be considered. As cardiovascular morbidity and mortality is increased in patients with RA, it would be useful to determine whether RA should be considered as an independent cardiovascular risk factor or as a major risk factor like diabetes that warrants more aggressive cardiac prevention measures.
25160808 Validation of the Comprehensive ICF Core Set for rheumatoid arthritis: the perspective of 2008 The 'Comprehensive ICF Core Set for rheumatoid arthritis (RA)' is an application of the International Classification of Functioning, Disability and Health (ICF) and represents the typical spectrum of problems in functioning of patients with RA. The objective of this study was to validate this ICF Core Set from the perspective of psychologists. Psychologists experienced in RA treatment were asked about the problems of RA patients, treated by psychologists, in a three-round survey using the Delphi technique. Responses were linked to the ICF. Twenty psychologists in five countries gave a total of 303 responses that were linked to 65 different ICF categories. Fifteen responses were linked to the not yet developed ICF component personal factors and nine were not covered by ICF. Overall, 66% of the ICF categories linked to the responses of the psychologists were represented by the Comprehensive ICF Core Set for RA. Several responses that were not covered need to be investigated further.
17223651 Characterisation of a dendritic cell subset in synovial tissue which strongly expresses Ja 2007 Aug OBJECTIVES: To characterise the phenotype of the putative dendritic cells strongly expressing Jak3 and STAT4, which have been previously identified in the synovial tissue of patients with active rheumatoid arthritis (RA). METHODS: Synovial biopsy specimens were obtained at arthroscopy from 30 patients with active RA (42 synovial biopsies). Immunohistological analysis was performed using monoclonal antibodies to detect dendritic cell subsets, including activation markers and cytokines relevant to dendritic cell function. Co-localisation of cell surface markers and cytokines was assessed primarily using sequential sections, with results confirmed by dual immunohistochemistry and immunofluorescence with confocal microscopy. RESULTS: The dendritic cells identified in RA synovial tissue that strongly express Jak3 also strongly express STAT4 and STAT 6 and are correlated with the presence of serum rheumatoid factor. These cells are not confined to a single dendritic cell subset, with cells having phenotypes consistent with both myeloid- and plasmacytoid-type dendritic cells. The activation status of these dendritic cells suggests that they are maturing or mature dendritic cells. These dendritic cells produce IL12 as well as interferon alpha and gamma. CONCLUSIONS: The close correlation of these dendritic cells with the presence of serum rheumatoid factor, a prognostic factor for worse disease outcome, and the strong expression by these cells of components of the Jak/STAT transcription factor pathway suggest a potential therapeutic target for the treatment of RA.
17882240 What can be learned using microarrays? 2007 Oct Whole-genome microarrays identify large numbers of gene expression changes that appear specifically related to disease states such as antineutrophil cytoplasmic autoantibody (ANCA) and systemic lupus erythematosus. Although understanding this enormous volume of esoteric data is difficult, a few basic concepts regarding microarray studies can significantly improve the general reader's comprehension.
18322644 Efficacy and safety of tacrolimus treatment for rheumatoid arthritis patients undergoing h 2008 Rheumatoid arthritis (RA) is an autoimmune disorder characterized by progressive joint destruction that requires aggressive treatment using appropriate disease-modifying antirheumatic drugs (DMARDs). RA patients with renal failure, however, are intolerant to most DMARDs due to the potential toxicity. In Japan, tacrolimus was approved for the treatment of RA in 2005. Based on its pharmacokinetics, tacrolimus may be administered to the patients undergoing hemodialysis. We report two cases of RA patients on hemodialysis treated effectively and safely with tacrolimus.
18160851 Association of FOXJ1 polymorphisms with systemic lupus erythematosus and rheumatoid arthri 2007 Dec 31 The forkhead-box J1 (FOXJ1) transcription factor could suppress a spontaneous activation of T cells and B cells through an induction of IkappaBbeta that results in repression of NF-kappaB activity. In Foxj1 deficiency mice, systemic autoimmune inflammation is quite common symptom. Therefore, deregulated Foxj1 is supposed to be associated with autoimmune diseases and/or other inflammatory diseases. Previously, we identified that polymorphisms of human FOXJ1 gene (g.??460C>T, g.1805G>T and g.3375G>C) are associated with allergic rhinitis in a Korean population. In present study, we compared the genotype and allele frequencies of these SNPs between healthy controls and systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) patients. We also investigated the relationships between each genotype and the expression levels of anti- nuclear antibodies in SLE patients, and rheumatoid factor and anti-cyclic citrullinated peptide in RA patients. The frequencies of haplotypes constructed by these FOXJ1 SNPs were compared between controls and SLE (or RA) patients. The results of genotype and allele analysis showed that the prevalence of polymorphism g.3375G>C was associated with the susceptibility of SLE (P = 0.0072 and 0.0042, respectively). But no significant association was found with RA. In the haplotype analysis, however, the main CGG showed a weak association between controls and RA patients (P = 0.048).
18163491 Differences in synovial tissue infiltrates between anti-cyclic citrullinated peptide-posit 2008 Jan OBJECTIVE: To compare synovial tissue infiltrates from patients with anti-cyclic citrullinated peptide (anti-CCP)-positive rheumatoid arthritis (RA) with those from patients with anti-CCP-negative RA. METHODS: Synovial tissue samples were obtained arthroscopically from the inflamed knee joints of 57 patients with RA (34 of whom were anti-CCP positive) and examined for several histologic features along with immunohistologic expression of cell markers. Joint damage was assessed using the Kellgren/Lawrence (K/L) scale (range 0-4) on standard anteroposterior radiographs. In 31 patients (18 of whom were anti-CCP positive), synovial tissue was available from an earlier time point, allowing analysis of temporal changes. RESULTS: Synovial tissue from anti-CCP-positive patients was characterized by a higher mean number of infiltrating lymphocytes (61.6 versus 31.4/high-power field [hpf] [400x]; P=0.01), less extensive fibrosis (mean score of 1.2 versus 2.0; P=0.04), and a thinner synovial lining layer (mean score of 2.1 versus 3.3; P=0.002) compared with synovial tissue from anti-CCP-negative patients. Anti-CCP-positive patients expressed more CD3, CD8, CD45RO, and CXCL12. More anti-CCP-positive patients had a K/L score >1 compared with anti-CCP-negative patients. The difference in the mean lymphocyte counts was already present a mean of 3.8 years before the index biopsy (76.7 lymphocytes/hpf and 26.7 lymphocytes/hpf in anti-CCP-positive patients and anti-CCP-negative patients, respectively; P=0.008) and was independent of disease duration and K/L score. CONCLUSION: Synovitis in patients with anti-CCP-positive RA differs from that in patients with anti-CCP- negative RA, notably with respect to infiltrating lymphocytes, and is associated with a higher rate of local joint destruction.
18388525 Association of infections and tuberculosis with antitumor necrosis factor alpha therapy. 2008 May PURPOSE OF REVIEW: Rheumatoid arthritis patients have higher risk for infections due to comorbidities, underlying immunosuppression and use of glucocorticoids and disease modifying antirheumatic drugs. The association between treatment with antitumor necrosis factor alpha agents and serious infections, including opportunistic infections such as tuberculosis, in rheumatoid arthritis patients remains controversial. We present recent literature on this topic with a focus on clinical applications of this new data. RECENT FINDINGS: Prospective cohort studies and population-based registries have described the incidence and risk of serious infections in large rheumatoid arthritis patient populations of antitumor necrosis factor alpha users. Although some studies have suggested a one and one-half to two-fold increased risk, especially immediately after initiating the treatment, not all have shown an elevated risk for serious bacterial infections or tuberculosis. SUMMARY: Although antitumor necrosis factor alpha agents may be independent risk factors for infections there is an absolute low rate of infection in those treated with these agents (approximately 5 per 100 patient-years). Screening for latent tuberculosis with tuberculin skin testing is effective, and compliance with the recommendations for preventing this disease in recipients of antitumor necrosis factor alpha agents has partially decreased the risk of infections. Clinical suspicion toward developing infection in those being treated with antitumor necrosis factor alpha agents, particularly earlier in the treatment course, is important for effective management of patients.
18177923 Characteristics and outcome of connective tissue diseases in patients with sickle-cell dis 2008 Dec OBJECTIVES: To analyze the main characteristics of adults with sickle cell disease (SCD) and concurrent connective tissue disease (CTD). METHODS: A retrospective investigational study was performed. CTD was diagnosed according to standard international criteria. Severity of SCD was assessed by a clinical severity score. RESULTS: Thirty patients, 23 women (76%) and 7 men, with hemoglobin S/S (n = 25) or S/C (n = 5) SCD were included. The subtypes of CTD were rheumatoid arthritis (RA) (n = 15), definite systemic lupus erythematosus or "incomplete lupus" requiring treatment (n = 13), primary Sjögren's syndrome with central nervous system involvement (n = 1), and systemic sclerosis (n = 1). Twenty-five of the 30 patients (83%) received steroid treatment, and 15 (50%) received at least 1 immunosuppressive agent (methotrexate in 14 cases) to control CTD. Four RA patients were given antitumor necrosis factor (TNF)alpha and 1 was treated with rituximab without SCD exacerbation. After a median follow-up of 4.5 years [range: 6 months to 30 years] from CTD diagnosis, 11 of the 25 (44%) patients receiving steroids had at least 1 episode of severe infection (mostly due to Staphylococcus aureus or Escherichia coli). SCD exacerbated in 13 of the 30 (43%) patients after CTD onset; 12 of these patients were receiving prednisone and/or methotrexate. Six patients (20%) had died from sepsis (n = 2), stroke (n = 2), or acute chest syndrome (n = 2). CONCLUSIONS: CTD-related clinical manifestations and outcome were not particularly severe in patients with SCD. However, those with active CTD and undergoing steroid +/- methotrexate treatment had more serious SCD-related manifestations, a higher rate of severe infections, and an overall patient mortality rate of 20%. Thus, the management of patients with CTD and underlying SCD should consider the risk/benefit ratio of each treatment and steroid-sparing strategies should be implemented.
18328148 No influence of SLC22A4 C6607T and RUNX1 G24658C genotypic variants on the circulating car 2008 Jan OBJECTIVE: In a Japanese study, the C6607T SNP mapping to intron 1 of the SLC22A4 gene encoding the OCTN1 protein was found to be associated with rheumatoid arthritis. Similarly, a G24658C transversion in intron 6 of the gene encoding the RUNX1 transcription factor that regulates OCTN1 and also likely OCTN2 expression was also found to confer susceptibility to the disease. METHODS: We investigated the prevalence of these two SNPs by RFLP analysis in a cohort of 209 Hungarian rheumatoid arthritis patients, and 217 healthy controls. Since both the OCTN1 and OCTN2 play a central role in the transmembrane transport of carnitine, we also determined the quantitative serum carnitine ester profile by ESI tandem mass spectrometry. RESULTS: No statistically significant differences were found comparing the genotype prevalence rates between the patients and the controls for either the SLC22A4 genotypes or for the RUNX1 SNPs. There was no significant difference in the serum carnitine ester profile when the rheumatoid arthritis patients were compared with the controls; furthermore, no significant difference in the carnitine esters could be detected when genotype specific subgroups of the patients and the controls were studied. CONCLUSION: Data of the current study do not confirm the universal and population independent susceptibility role of the SLC22A4 C6607T and RUNX1 G24658C variants for rheumatoid arthritis; furthermore, the data presented here show, that there are no significant carnitine-metabolism associated functional consequences of the different genotypes evidenced by the lack of detectable differences in the carnitine ester profiles.