Associations of HLA‐DRB1 alleles with anti‐citrullinated protein antibody‐positive and anti‐citrullinated protein antibody‐negative rheumatoid arthritis in northern east part of Turkey

Aim: The aim of this study was to investigate the associations between human leukocyte antigen (HLA)‐DRB1 alleles with genetic susceptibility to rheumatoid arthritis (RA) and production of antibodies against cyclic citrullinated peptide (anti‐CCP antibody) and rheumatoid factor (RF) in Turkish RA patients. Methods: We studied 291 RA patients and 253 controls. Genotyping was performed by polymerase chain reaction with sequence‐specific oligonucleotide probes hybridization method. Serum levels of anti‐CCP antibody, IgM‐RF and high sensitive C‐reactive protein titers were measured by commercial kits using immunological methods. Results: We found that HLA‐DRB1*04 and *09 alleles were associated in anti‐CCP+ and anti‐CCP+ RA patients (P < 0.0001 and P < 0.001, respectively), while DRB1*01 and *04 were determined to be higher in RF+ RA patients (P < 0.001 and P < 0.0001, respectively). Moreover, DRB1*11 and DRB1*13 alleles were determined to be lower in RF and anti‐CCP/RF+ RA patients (P < 0.001 for both). HLA‐DRB1*04 was identified as a common responsible allele for susceptibility to the disease in anti‐CCP, RF and anti‐CCP/RF? RA patients (P = 0.0018, P = 0.0004 and P = 0.0023, respectively). HLA‐DRB1*13 allele alone was found to be protective against to anti‐CCP+ and RF? RA (P = 0.0003 and P = 0.006, respectively). On the contrary, there was no protective allele in anti‐CCP/RF? RA as well as anti‐CCP? RA patients. Conclusion: This study indicates that associate and protective HLA‐DRB1 allele distributions are different in autoantibody (anti‐CCP or RF or anti‐CCP/RF)+ RA and autoantibody? RA patients, with exceptions of DRB1*04 and DRB1*13.     

Melatonin attenuates TNF‐α and IL‐1β expression in synovial fibroblasts and diminishes cartilage degradation: Implications for the treatment of rheumatoid arthritis

The hormone melatonin has many properties, including antioxidant, anti‐inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose‐dependently inhibits tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β expression through the PI3K/AKT, ERK, and NF‐κB signaling pathways. We also identified that melatonin inhibits TNF‐α and IL‐1β production by upregulating miR‐3150a‐3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast‐like synoviocytes confirmed that the MT1 receptor is needed for the anti‐inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen‐induced arthritis mouse model. Our results indicate that melatonin ameliorates RA by inhibiting TNF‐α and IL‐1β production through downregulation of the PI3K/AKT, ERK, NF‐κB signaling pathways, as well as miR‐3150a‐3p overexpression. The role of melatonin as an adjuvant treatment in patients with RA deserves further clinical studies.     

Genotyping for disease associated HLA DR β1 alleles and the need for early joint surgery in rheumatoid arthritis: a quantitative evaluation

OBJECTIVE: To determine the value of HLA DR beta 1 disease associated epitope (DAE) and erythrocyte sedimentation (ESR) in predicting the need for major joint replacement in rheumatoid arthritis (RA). METHODS: Sixty five RA patients who had undergone hip, knee or shoulder arthroplasty within 15 years of disease onset and 65 who had not. HLA DR beta 1 genotype was determined by polymerase chain reaction. ESR at first hospital visit was noted. RESULTS: Significantly more patients with two DAE required surgery, (32% v 9%), chi 2 = 13.9, p = 0.001, odds ratio = 5.4 (95% CI: 1.8, 16). Sensitivity was poor, 32%, specificity high, 91%. Presentation ESR was higher in surgery patients compared with non-surgery patients, 52 mm 1st h v 25 mm 1st h, p < 0.001, but was independent of DAE status. Sensitivity of an ESR of 30 mm 1st h was 75%, specificity 53%. CONCLUSION: The presence of two DAE is a risk factor for major joint surgery in RA and is independent of ESR, whereas in those with one or no DAE, a high ESR is an important predictor.     

Experience of antitumor necrosis factor‐α therapies in Taiwan

Background: Etanercept (Enbrel), was the first approved biologics in Taiwan for rheumatoid arthritis (RA), juvenile RA (JRA), psoriatic arthritis and ankylosing spondylitis. Approximately 500 patients with RA were under etanercept therapy by April 2006. Aim: We aimed to review the current status of biological agents use in the treatment of rheumatic diseases in Taiwan. Methods: MEDLINE database (January 1966 to February 2006) was searched by MeSH terms, limited to Taiwan by author affiliations. All known principal clinical investigators and pharmaceutical companies in Taiwan were contacted for unpublished information about this issue. Results: Six articles including two clinical trials, two case series and two preclinical studies were found in MEDLINE since January 1966. A 12‐week double‐blind placebo‐controlled study of 58 patients with active adult RA in Taiwan revealed better efficacy than results in Western countries. For JRA, two studies reported good results in polyarticular type JRA but fair response in systemic type. Adalimumab (Humira, Abbott) and Alefacept (Ameviev, Biogen) had completed their local trials in RA and psoriasis but they are not yet available in Taiwan. Widespread usage of biologics has been limited due to restricted insurance coverage policy only to the refractory patients with RA. Some herbs demonstrating TNF‐α inhibition properties are under exploratory clinical trials. Conclusions: Etanercept showed better efficacy in patients with adult RA in Taiwan than Western countries. Some herbs demonstrated TNF‐α inhibition and are under laboratory and clinical investigations.     

Prevalence of allo‐immunization anti‐HLA and anti‐integrin αIIbβ3 in Glanzmann Thromboasthenia patients

Summary. Platelet transfusions, main therapy of Glanzmann Thromboasthenia (GT), can induce an allo‐immunization against human leucocyte antigen and integrin αIIbβ3. We have investigated in our GT patients the rate of allo‐immunization and of refractoriness to platelet transfusions. From 1975 until December 2005, we have followed 17 GT patients: 14 type 1, 3 variant type; nine females, eight males; median age at diagnosis 9.8 years (range 1–44.5); median age at the time of the study 35.5 years (range 23.6–68.5). In our patients, 121 bleeding episodes occurred (24 severe, 37 moderate, and 60 mild). Ten major and 22 minor surgical procedures have been performed. Two spontaneous deliveries and three caesarian sections with five live births were performed; moreover, one late foetal loss occurred, and one voluntary abortion was performed. Sixteen of 17 patients have been transfused at least once in life with platelets and/or red blood cells (RBC). All transfused patients have been investigated for the presence of anti‐HLA and anti‐integrin αIIbβ3 allo‐antibodies. The positiveness of allo‐antibodies has been demonstrated in 4/16 transfused patients (25%): isolated for anti‐HLA in two; isolated for anti‐integrin αIIbβ3 in one; and combined in one. In spite of the presence of allo‐antibodies, platelet transfusions have always been effective and the haemostasis was not compromised.     

Self‐reported outcomes during treatment with tumour necrosis factor α inhibitors in patients with rheumatoid arthritis

Objective: To study how patients with rheumatoid arthritis (RA) self‐report their experience of disease‐related symptoms (fatigue, morning stiffness, pain) and their ability to cope with everyday life (capacity) using a nurse‐led structured follow‐up during the first year after starting treatment with tumour necrosis factor α (TNF‐α) inhibitors. Methods: Thirty‐nine patients, who were being treated for their RA in our outpatient rheumatology clinic and were beginning treatment with TNF‐α inhibitors, agreed to evaluate and self‐report their experience of fatigue, morning stiffness, pain, and capacity using the visual analogue scale (VAS) every third month during their first year of treatment. A quantitative method was used to study the changes in these four variables. In addition, at the same time, we studied the relationship between self‐reported capacity and each of the three symptoms. Results: After 12 months' treatment with TNF‐α inhibitors, the change (median interquartile range [IQR]) measured with VAS was ?14 (?38, ?7) mm for fatigue, ?22 (?47, ?4) mm for morning stiffness, ?28 (?50, 0) mm for pain and ?27 (?48, ?6) mm for capacity. All changes were statistically significant (p < 0.001). Baseline and 12 months' capacity correlated significantly with fatigue, morning stiffness and pain (all p < 0.01). In addition, the median change in self‐reported capacity correlated significantly with the median change in each of the three symptoms (p < 0.01). Conclusion: During the first year of treatment with TNF‐α inhibitors, patients reported decreased fatigue, morning stiffness and pain, while their capacity increased. The increased capacity rate closely followed the decrease in symptom rate. Copyright © 2009 John Wiley & Sons, Ltd.     

Laboratory diagnosis of a compound heterozygosity for Hb Hekinan [α27(B8) Glu‐Asp] and a deletional α‐thalassaemia 2 in Thailand

We report the haematological and molecular characterization of a previously undescribed condition of compound heterozygosity for haemoglobin (Hb) Hekinan [α27(B8) Glu‐Asp] and a deletional α‐thalassaemia 2 detected in a Thai individual. Hb analysis demonstrated that although this Hb variant co‐migrates with Hb A on cellulose acetate electrophoresis and cation‐exchange high‐performance liquid chromatography (HPLC), the HPLC procedure using a weak cation‐exchange material with polyaspartic acid could clearly differentiate the two Hb. The variant could then be confirmed using the polymerase chain reaction‐restriction fragment‐length polymorphism (PCR‐RFLP) analysis of the amplified α1‐globin gene.