Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding β (S100β) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100β, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100β levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51 ± 1.36 vs. 5.24 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/mL), and S100β protein (2.24 ± 0.50 vs. 0.47 ± 0.06) than controls (all p < 0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100β levels than healthy controls (all p < 0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r = ?0.42, p = 0.005), Stroop Color-Word (r = ?0.48, p = 0.004), and N-Back Total scores (r = ?0.59, p < 0.0001) and positively with Trail Making Test B (TMB, r = 0.53, p = 0.001). Negative correlation was found between levels of anti-MOG and DVR (r = ?0.64, p < 0.0001), N-Back Total scores (r = ?0.35, p = 0.03), Stroop Color-Word (r = ?0.51, p = 0.001), and positively with TMB (r = 0.50, p = 0.003). S100β levels were associated with DVR (r = ?0.51, p = 0.002), TMB (r = 0.46, p = 0.008), Stroop Color-Word (r = ?0.67, p < 0.0001), and N-Back Total (r = ?0.52, p = 0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100β levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.     

HLA-DRB1 alleles genotyping in patients with rheumatoid arthritis in Chinese.

Objective: To explore the role of HLA-DRB_1 genes in the development of rheumatoid arthritis (RA) and the correlations between HLA-DR alleles and clinical manifestations of patients with RA. Methods: 86 patients and 106 race matched controls in whom HLADR typing was performed by the method of DNA amplification with sequence-specific primers (PCR-SSP)     

Sauvé–Kapandji procedure with headless compression screw in patients with rheumatoid arthritis

Objective: We examined the surgical outcomes of the Sauvé–Kapandji (S–K) procedure using a headless compression screw and a metal cancellous screw in patients with rheumatoid arthritis (RA).

Methods: This retrospective study included 41 RA patients who underwent the S–K procedure for distal radioulnar joint disorders with two screws: headless compression screws (HCS group, n?=?20) and cannulated cancellous screws (CCS group, n?=?21). Clinical and radiographic outcomes were assessed 1 year after surgery. Radiographic outcomes included bony union of the distal radioulnar joint (DRUJ), bone resorption around the screw, a screw back-out, and use of additional K-wire. We investigated any complications related to the screw head.

Results: All 20 patients in the HCS group showed bone fusion of the DRUJ. In the CCS group, an asymptomatic non-union was observed in one patient and additional K-wire was needed to stabilize the DRUJ in three patients. No patients complained of any complications related to the screw head in the HCS group, while the CCS group demonstrated the hardware protrusion in two patients who complained of tenderness or discomfort at the screw head.

Conclusions: The use of a headless compression screw in the S–K procedure is useful in patients with RA.     

Leflunomide in dialysis patients with rheumatoid arthritis—a pharmacokinetic study

Pharmacokinetic data of disease modifying antirheumatic drugs during hemodialysis are limited to sulfasalazine, methotrexate, and cyclosporine. Only respective anecdotal data have been reported on leflunomide. We repeatedly measured teriflunomide (A77-1726), the active metabolite of leflunomide, during standard hemodialysis sessions and calculated teriflunomide clearances in five patients with rheumatoid arthritis (RA) and end-stage renal disease. The calculated teriflunomide clearances during a standardized dialysis session of 3–4.5 h at a blood flow rate of 160–300 ml/min were between 0 and 4.3 ml/min, the mean clearances of the total dialysis ranged between 1.1 and 3.4 ml/min. Total amount of teriflunomide removed was 5.8–8.8 μg per dialysis session. Dialytic removal of the active metabolite of leflunomide, teriflunomide (A77-1726), is negligible. Leflunomide can be used for RA patients on chronic dialysis without any dosage modification.     

Gold metabolism in patients with rheumatoid arthritis treated with gold compounds—reinvestigated

Absorption of gold from injected sites occurs rapidly, reaching its peak in blood between 4 and 6 hours. In plasma, 95% of gold is bound to albumin. Three patients that were studied from the beginning of weekly therapy showed a progressive stepwise rise in plasma gold levels up to the sixth week. Urinary excretion was greatest during the first day postinjection while fecal excretion was greatest during the middle of the week. The blood levels, as well as excretion, varied from patient to patient. Patients on maintenance therapy excreted 39, 16, 12 and 10% of the injected dose in the first, second, third and fourth weeks postinjection, respectively. There were no significant differences in blood gold levels in patients who showed a good therapeutic response, no therapeutic benefit or toxicity.     

Evaluation of abatacept in biologic-naïve patients with active rheumatoid arthritis

This article reviews the efficacy, safety, and tolerability of abatacept plus methotrexate in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate who are naïve to biologic disease-modifying antirheumatic drugs (DMARDs). Data from the randomized, double-blind, placebo-controlled Abatacept in Inadequate Responders to Methotrexate, Abatacept or Infliximab vs Placebo, a Trial for Tolerability, Efficacy, and Safety in Treating Rheumatoid Arthritis, and phase IIb dose-finding trials and their long-term extensions are reviewed. Abatacept plus methotrexate significantly improved clinical responses, physical function, and health-related quality of life compared with methotrexate alone. More patients receiving abatacept plus methotrexate than methotrexate monotherapy achieved a low disease activity state or remission. Radiographic progression of the disease was significantly slowed in the abatacept plus methotrexate arms. Abatacept plus methotrexate was generally well tolerated with no clinically significant safety issues identified. The beneficial effects of abatacept plus methotrexate were sustained long term in extension studies, and no new tolerability or safety issues were evident. Abatacept in combination with methotrexate is an effective, safe, and well-tolerated long-term therapy in biologic-naïve patients with active RA and an inadequate response to methotrexate. Abatacept could be considered as a first-line biologic DMARD in the treatment of RA.     

The −590 IL-4 promoter polymorphism in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines play an important role. The aim of the present study was to evaluate the –590 IL-4 promoter polymorphism in patients with RA and its association with disease activity and severity. We enrolled 94 patients with RA diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction amplification was used for analysis of the polymorphism at position –590 of the promoter of the IL-4 gene. The distribution of IL-4 genotypes in RA patients did not differ from control subjects. Nevertheless, the active form of RA was more frequently diagnosed in patients with T allele (genotypes CT and TT) as compared with homozygous CC patients. Moreover, in carriers of the T allele, parameters of disease activity (DAS 28 score, ESR, number of swollen and tender joints) were significantly increased. We suggest that the IL-4 –590 promoter polymorphism may be a genetic risk factor for RA severity.     

Pharmacokinetic study and Fcγ receptor gene analysis in two patients with rheumatoid arthritis controlled by low-dose infliximab

The main aim of this study is to investigate the pharmacokinetics of infliximab and Fcγ receptor (FcγR) polymorphism in two patients with rheumatoid arthritis (RA) who were well controlled by low-dose infliximab. A 57-year-old woman (Patient 1) and a 67-year-old woman (Patient 2) had active RA despite methotrexate and prednisolone treatments. They improved after the addition of infliximab (3 mg/kg), but developed pneumonia and sepsis, respectively. Although the infliximab doses were reduced to 1.5 mg/kg and 1 mg/kg, respectively, clinical improvements were maintained. Blood samples were obtained at 1 h after infliximab administration and at eight weeks (just before the next dose). The elimination half-life was determined by the serum concentration of infliximab. We also analyzed the polymorphisms of FcγRIIA, FcγRIIIA, and FcγRIIIB for the genomic DNA samples from the two patients and three controls. Amplification of the FcγR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. Decresed clearance of infliximab was proven by a pharmacokinetic study of these patients under low-dose infliximab therapy. 131H/H (FcγRIIA) and 176F/F (FcγRIIIA) were detected in both patients. NA1/NA2 and NA2/NA2 (FcγRIIIB) were detected in Patients 1 and 2, respectively. These patients were well controlled over the long term by low-dose infliximab. The mechanism of the reduced clearance of infliximab might possibly be explained in part by the FcγR polymorphisms.     

Pharmacokinetic study and Fcγ receptor gene analysis in two patients with rheumatoid arthritis controlled by low-dose infliximab

Abstract

The main aim of this study is to investigate the pharmacokinetics of infliximab and Fcγ receptor (FcγR) polymorphism in two patients with rheumatoid arthritis (RA) who were well controlled by low-dose infliximab. A 57-year-old woman (Patient 1) and a 67-year-old woman (Patient 2) had active RA despite methotrexate and prednisolone treatments. They improved after the addition of infliximab (3 mg/kg), but developed pneumonia and sepsis, respectively. Although the infliximab doses were reduced to 1.5 mg/kg and 1 mg/kg, respectively, clinical improvements were maintained. Blood samples were obtained at 1 h after infliximab administration and at eight weeks (just before the next dose). The elimination half-life was determined by the serum concentration of infliximab. We also analyzed the polymorphisms of FcγRIIA, FcγRIIIA, and FcγRIIIB for the genomic DNA samples from the two patients and three controls. Amplification of the FcγR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. Decresed clearance of infliximab was proven by a pharmacokinetic study of these patients under low-dose infliximab therapy. 131H/H (FcγRIIA) and 176F/F (FcγRIIIA) were detected in both patients. NA1/NA2 and NA2/NA2 (FcγRIIIB) were detected in Patients 1 and 2, respectively. These patients were well controlled over the long term by low-dose infliximab. The mechanism of the reduced clearance of infliximab might possibly be explained in part by the FcγR polymorphisms.     

Allelic frequency of the MCP-1 promoter −2518 polymorphism in the Turkish population and in Turkish patients with juvenile rheumatoid arthritis

Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene −2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the −2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the −2518 (G/A) MCP-1 gene polymorphism (p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA (p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the −2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis (p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference.     

How should we manage low-dose methotrexate-induced pancytopenia in patients with rheumatoid arthritis?

Clinical Rheumatology - Low-dose methotrexate (ld-MTX) that is administered during rheumatoid arthritis (RA) treatment has hematological adverse effects such as pancytopenia, although rare....     

Is dermatomyositis in patients with rheumatoid arthritis induced by anti-TNF-α therapy?

Clinical Rheumatology -     

QT Dispersion in rheumatoid arthritis patients with and without sjögren's syndrome

The aim of this study was to assess the effect of secondary Sjögren's syndrome (SjS) on QT dispersion and corrected QT dispersion in patients with rheumatoid arthritis (RA). We performed electrocardiography and Doppler echocardiography on 58 patients with RA whom we divided into two groups according to the presence of secondary SjS, and on 29 healthy controls. All patients revealed significantly longer QT dispersion and corrected QT dispersion values (P < 0.05). Diastolic function variables were significantly different in all patients compared to controls. QT dispersion and corrected QT dispersion values were significantly longer in RA patients with secondary SjS than in those without. We concluded that secondary SjS could be a cardiovascular risk factor contributing to the well documented cardivascular disease in RA patients.     

Tumour necrosis factor a −308 promoter polymorphism in patients with rheumatoid arthritis

There are controversial reports that TNF-a promoter polymorphism may be an independent marker of susceptibility to rheumatoid arthritis (RA). We used Polymerase chain reaction amplification and Restriction fragment length polymorphism for analysis of the polymorphism at position -308 in promoter of TNF-α gene in 34 patients with RA and 30 healthy individuals. Distribution of TNF-genotypes in RA patients did not differ from that in controls. Moreover, there was apparent association between the -308 TNF-α polymorphism and erosions in hand x-Ray was found (P value = 0.043). We suggest that TNF-α -308 promoter polymorphism is not a genetic risk factor for RA susceptibility but may be associated with radiographic damage in rheumatoid patients. All work was funded by the Chancellor for Research of Mashhad University of Medical Science.