Genetic variation in the SLC19A1 gene and methotrexate toxicity in rheumatoid arthritis patients.

Aim: We investigated the clinical relevance of SLC19A1 genetic variability for methotrexate (MTX) toxicity in rheumatoid arthritis patients using a haplotype-based approach.

Patients & Methods: Two hundred and twelve unrelated rheumatoid arthritis patients and 89 lymphoblastoid cell lines were used to investigate the effect of SLC19A1 SNPs and haplotypes on MTX adverse events and treatment discontinuation.

Results: Two putatively functional SNPs in high linkage disequilibrium, rs1051266 and rs1131596, were associated with protection (hazard ratio: 0.

Autoimmune response following influenza vaccination in patients with autoimmune inflammatory rheumatic disease.

Vaccines have undoubtedly brought overwhelming benefits to mankind and are considered safe and effective. Nevertheless, they can occasionally stimulate autoantibody production or even a recently defined syndrome known as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). There is scarce data regarding autoimmune response after seasonal/influenza A (H1N1) vaccine in patients with autoimmune inflammatory rheumatic disease (AIRD).

Osteoblastogenesis and adipogenesis are higher in osteoarthritic than in osteoporotic bone tissue.

Background And Aims: New data show that increased adipogenesis in bone marrow may decrease osteoblastogenesis, resulting in osteoporosis (OP). Runt-related transcription factor 2 (RUNX2) and peroxisome proliferator-activated receptor γ (PPARγ) are two main transcriptional regulators controlling osteoblastogenesis and adipogenesis from the same precursor cell in bone-the mesenchymal stem cell. Because osteoarthritis (OA) and OP present the opposing bone phenotype, our aim was to determine whether the expression of selected adipogenic genes is lower in OA compared to OP bone tissue.

A microarray based identification of osteoporosis-related genes in primary culture of human osteoblasts.

Genetic factors influencing the pathogenesis of osteoporosis are still largely unknown. We employed genome-wide gene expression approach in order to discover novel genes involved in the pathogenesis of osteoporosis. To this end, primary cultures of osteoblasts isolated from osteoporotic and non-osteoporotic human bone tissue samples were prepared.

Investigation of the influence of CYP1A2 and CYP2C19 genetic polymorphism on 2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide (A77 1726) pharmacokinetics in leflunomide-treated patients with rheumatoid arthritis.

Leflunomide is a disease-modifying antirheumatic drug used for the treatment of rheumatoid arthritis (RA). Cytochromes P450, mainly CYP1A2 and CYP2C19, may be involved in the transformation of leflunomide to leflunomide metabolite (A77 1726, 2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]-2-butenamide). The aim of this study was to investigate whether genetic polymorphisms in CYP1A2 and CYP2C19 influence leflunomide pharmacokinetics, treatment response, and the occurrence of adverse drug reactions (ADRs).

Genetic polymorphisms of glutathione S-transferases and disease activity of rheumatoid arthritis.

Objectives: Glutathione S-transferases (GST); GST-mu1 (GSTM1), GST-pi1 (GSTP1) and GST-theta1 (GSTT1) have peroxidase activity towards cytotoxic metabolites produced in inflammatory reactions, the main feature of rheumatoid arthritis (RA). Genetic polymorphisms in GSTM1, GSTP1 and GSTT1 modify the enzyme conjugation capacity and may be associated with the activity of RA.

Methods: A genotyping approach was used to analyze GSTM1-0, GSTT1-0 and GSTP1 Ile105Val and Ala114Val polymorphisms in 213 RA patients.

Genetic polymorphisms modifying oxidative stress are associated with disease activity in rheumatoid arthritis patients.

Reactive oxygen and nitrogen species are involved in the pathology of rheumatoid arthritis (RA). Polymorphisms in genes coding for superoxide dismutases (SOD2 and SOD3), catalase (CAT), tumor necrosis factor-alpha (TNFA) and inducible NO synthase (NOS2A) may influence RA activity. We determined SOD2 Ala-9Val, SOD3 Arg213Gly, CAT C-262T, TNFA G-308A, TNFA C-857T and NOS2A (CCTTT) (n)polymorphisms in 327 RA patients.

Genetic determinants of methotrexate toxicity in rheumatoid arthritis patients: a study of polymorphisms affecting methotrexate transport and folate metabolism.

Objective: Methotrexate (MTX) is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 A80G), P-glycoprotein (MDR1 G2677T>A/C and C3435T), 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TS 2R-->3R), methionine synthase (MS A2756G) and methionine synthase reductase (MTRR A66G) modify MTX transport and metabolic effects and may influence the treatment response.

Methods: A genotyping approach was used to determine the studied polymorphisms in 213 RA patients.

Genetic polymorphism of CYP1A2 and the toxicity of leflunomide treatment in rheumatoid arthritis patients.

Objective: Leflunomide is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA). In vitro studies demonstrated that cytochromes P450 (CYPs), mainly CYP1A2 and CYP2C19, might be involved in leflunomide activation. The aim of our study was to investigate whether genetic polymorphisms of CYP1A2, CYP2C19, and CYP2C9 influence leflunomide toxicity.

Cathepsin K predicts femoral neck bone mineral density change in nonosteoporotic peri- and early postmenopausal women.

Objective: Cathepsin K is a cysteine protease that plays an essential role in organic bone matrix degradation. The aim of our study was to seek correlation of serum cathepsin K levels and a change in bone mineral density (BMD) over a 3-year period in a population of healthy nonosteoporotic women. The secondary end points were the correlations of serum cathepsin K with cross-sectional BMD and with other serum bone turnover markers and age.

Expression of bone resorption genes in osteoarthritis and in osteoporosis.

Cathepsin K and MMP-9 are considered to be the most abundant proteases in osteoclasts. TRAP is a marker for osteoclasts, and there is increasing evidence of its proteolytic role in bone resorption. RANKL is a recently discovered regulator of osteoclast maturation and activity and induces expression of many genes.

Subcutaneous infection with Pseudallescheria boydii in an immunocompromised patient.

With the broad employment of immunosuppressive therapy, the incidence of Pseudallescheria boydii infections is rising. We report a first case of the localized subcutaneous P. boydii infection in a patient with microscopic polyangiitis.

EULAR response criteria for polymyalgia rheumatica: results of an initiative of the European Collaborating Polymyalgia Rheumatica Group (subcommittee of ESCISIT).

Objective: To develop response criteria for polymyalgia rheumatica (PMR) for monitoring treatment and comparing alternative treatments regimens.

Methods: 76 patients, mean (SD) age 68.7 (7.

The contribution of HLA-DQB1 coding and QBP promoter alleles to anti-Ro alone autoantibody response in systemic lupus erythematosus.

Objective: To analyse the influence of HLA-DR, DQ and corresponding DQA1 and DQB1 promoter alleles (QAP and QBP) on the anti-Ro alone autoantibody response in systemic lupus erythematosus (SLE).

Methods: Sixty-five unrelated anti-La antibody-negative SLE patients, 37 of them with and 28 without anti-Ro antibodies, were included. Anti-Ro antibodies were determined by both counter-immunoelectrophoresis and enzyme-linked immunosorbent assay.

Systemic lupus erythematosus. Disease outcome in patients with a disease duration of at least 10 years: second evaluation.

Data related to the disease course of patients with systemic lupus erythematosus (SLE) with special attention to the persistence of disease activity in the long term are scarce. At this moment reliable figures are only known about the survival rate as a measure of outcome. The aim of this multicenter study was to describe the outcome of SLE patients with a disease duration of greater than 10 y.

Incomplete lupus erythematosus: results of a multicentre study under the supervision of the EULAR Standing Committee on International Clinical Studies Including Therapeutic Trials (ESCISIT).

Objective: Patients characterized with antinuclear antibodies (ANA) and disease symptoms related to one organ system can be described as having incomplete systemic lupus erythematosus (SLE). The aim of this multicentre study was to describe the outcome of these so-called incomplete SLE patients. Two aspects of the outcome were studied: (i) the disease course, defined by the presence or absence of clinical symptoms; and (ii) the number of patients that eventually developed full SLE.

Recurrent sepsis and seronegative arthritis in a patient with a selective IgG3 deficiency.

In a sixty-one-year-old patient with chronic polyarthritis, two life-threatening septic events were observed over a period of 6 months. The patient also had a selective IgG3 deficiency. The susceptibility to infection and chronic polyarthritis observed in this patient were very likely a consequence of the selective IgG3 deficiency.

Systemic lupus erythematosus: clinical features in patients with a disease duration of over 10 years, first evaluation.

Objective: Most information available about the disease course of patients with systemic lupus erythematosus (SLE) is restricted to the first 5 yr after disease onset. Data about the disease course 10 yr after disease onset are rare. The aim of this multicentre study was to describe the outcome of SLE patients with a disease duration of >10 yr.

Prevalence of Sjögren's syndrome in Slovenia.

Objective: The aim of our study was to determine the prevalence of Sjögren's syndrome (SS) in Slovenia.

Methods: A total of 889 randomly selected adults were invited to take part in our study. The classification of SS was based on the validated criteria reported by a multicentre study performed in Europe.

Contrast enhanced Gd-DTPA magnetic resonance imaging in the evaluation of rheumatoid arthritis during a clinical trial with DMARDs. A prospective two-year follow-up study on hand joints in 31 patients.

Objective: The aim of this prospective 24-month follow-up study was to compare clinical features with radiological and magnetic resonance imaging (MRI) findings in evaluating synovial proliferation in the hand joints of 31 patients with rheumatoid arthritis (RA). A single joint was used for the follow-up of each patient.

Methods: Thirty-one small hand joints were examined by conventional radiography and MRI before and after 24 months of treatment.

Prognostic value of contrast enhanced Gd-DTPA MRI for development of bone erosive changes in rheumatoid arthritis.

Conventional radiograms have been used to quantitate the progression of rheumatoid arthritis, mainly through the assessment of bone erosions, but this approach has many limitations. It has been suggested that an advantage of contrast-enhanced Gd-DTPA MRI over radiography may be its prognostic value due to its ability to show the natural history of active destructive to inactive fibrous pannus. The aim of this study was to evaluate the possible prognostic value of MRI for future development of bone erosive changes in small hand joints in patients with RA.

[Gold salt alveolitis in 3 patients with rheumatoid arthritis].

Background: When the characteristic symptoms for an interstitial pulmonary disease arise in patients with rheumatoid arthritis, a drug-induced alveolitis should be considered in the differential diagnosis. In such cases, the administration of the drug and gold salts should be stopped.

Patients And Methods: The cases of three patients with rheumatoid arthritis (RA) who had been treated with gold salts for 2 months (A), 23 months (B), and 36 months (C) are presented.