Rheumatoid Arthritis: Calgary

Luft LM, Barr SG, Martin LO, Chan EK, Fritzler MJ. · Department of Medicine, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. · J Rheumatol. · Pubmed #14719202 No free full text.

Abstract: OBJECTIVE: Sjögren's syndrome (SS) has been reported in up to 15% of patients with biopsy proven celiac disease (CD). The diagnosis of CD in the setting of SS and other systemic rheumatic diseases can be difficult because they are often associated with a number of gastrointestinal symptoms and diseases. Although the diagnosis of CD is often confirmed by a small bowel biopsy, marker autoantibodies directed against the endomysium of transitional epithelium (EMA) and tissue transglutaminase (tTG) are highly correlated with biopsy-proven disease and serve as a valuable screening test. We used an IgA-anti-tissue transglutaminase antibody (anti-tTG) ELISA to assess the prevalence of anti-tTG in an unselected cohort of patients with SS and other systemic rheumatic diseases. METHODS: Sera from 50 patients with SS, 50 with systemic lupus erythematosus (SLE), 50 with rheumatoid arthritis (RA), 30 with systemic sclerosis (SSc), and 50 healthy controls were tested for autoantibodies to tTG. A comparison group of 40 sera from patients with biopsy-confirmed CD was also included. IgA anti-tTG was measured by a commercially available ELISA kit (Inova, San Diego, CA) that employs purified tTG. RESULTS: Six of the 50 (12%) IgA sufficient SS patients had anti-tTG compared to 2 (4%) normal sera, 3 (6%) SLE, 2 (7%) SSc, and 1 (2%) RA. By comparison, in the CD cohort, 33 (83%) had anti-tTG. Five of 6 SS patients with anti-tTG had symptoms, signs, or small bowel biopsy findings consistent with a diagnosis of CD. IgA anti-tTG and EMA were accompanied by other IgA autoantibodies in SS sera. CONCLUSION: Anti-tTG ELISA is a reliable method to indicate a coexisting diagnosis of CD in patients with SS. Interestingly, the frequency of false positive tTG tests in any of the systemic rheumatic diseases is not significantly greater than in controls. Further, our study shows that anti-tTG is more prevalent in SS than in other systemic rheumatic diseases. The tTG ELISA may be used as a screening test to identify patients with SS who are at risk and require further evaluation for the presence of CD.

Turchin I, Adams SP. · Faculty of Medicine, University of Calgary, Alberta. · Can Fam Physician. · Pubmed #14649981 links to  free full text

This publication has no abstract.

Eystathioy T, Chan EK, Takeuchi K, Mahler M, Luft LM, Zochodne DW, Fritzler MJ. · Department of Medicine, University of Calgary, 3330 Hospital Dr. N.W., Calgary, AB, T2N-4N1, Canada. · J Mol Med. · Pubmed #14598044 No free full text.

Abstract: A novel autoantigen named GW182 was recently identified when the serum from a patient with a sensory ataxic polyneuropathy was used to immunoscreen a HeLa cDNA library. Unique features of the GW182 protein include 39 repeats of glycine (G) and tryptophan (W) residues, binding to a subset of messenger RNA and localization to unique structures within the cytoplasm that were designated GW bodies (GWBs). The goal of the present study was to identify the clinical features of patients with anti-GW182 antibodies and to characterize the B cell anti-GW182 response by defining the epitopes bound by human autoantibodies. The most common clinical diagnosis of patients with anti-GW182 antibodies was Sjögren's syndrome followed by mixed motor/sensory neuropathy, and systemic lupus erythematosus. Of interest, 5 (28%), 9 (50%), and 3 (17%) of the 18 sera that react with GWBs had autoantibodies to the GW182 and the 52 kDa and 60 kDa SS-A/Ro autoantigens, respectively. Epitopes bound by the human autoantibodies were mapped to the GW-rich middle part of the protein, the non-GW rich region, and the C-terminus of GW182 protein. None of the GW182 epitopes had significant sequence similarities to other known proteins. GW182 represents a new category of ribonucleoprotein autoantigens.

Westaway MD, Stratford P, Symons B. · Faculty of Kinesiology, University of Calgary, Alberta, Canada. · Man Ther. · Pubmed #12890441 No free full text.

This publication has no abstract.

Hanley DA, Brown JP, Tenenhouse A, Olszynski WP, Ioannidis G, Berger C, Prior JC, Pickard L, Murray TM, Anastassiades T, Kirkland S, Joyce C, Joseph L, Papaioannou A, Jackson SA, Poliquin S, Adachi JD, Anonymous00168. · Department of Medicine, University of Calgary. Calgary, Alberta, Canada. · J Bone Miner Res. · Pubmed #12674340 No free full text.

Abstract: This cross-sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population-based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self-reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Paget's disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments. The differences were most notable at the lumbar spine (+0.053 g/cm2), femoral neck (+0.028 g/cm2), and trochanter (+0.025 g/cm2) in women, and at the femoral neck (+0.025 g/cm2) in men. Hypertension was also associated with higher bone mineral density measurements for both women and men. The differences were most pronounced at the lumbar spine (+0.022 g/cm2) and femoral neck (+0.007 g/cm2) in women and at the lumbar spine (+0.028 g/cm2) in men. Although results were statistically inconclusive, men reporting versus not reporting past nephrolithiasis appeared to have clinically relevant lower bone mineral density values. Bone mineral density differences were -0.022, -0.015, and -0.016 g/cm2 at the lumbar spine, femoral neck, and trochanter, respectively. Disease conditions were not strongly associated with vertebral deformities. In summary, these cross-sectional population-based data show that type 2 diabetes and hypertension are associated with higher bone mineral density in women and men, and nephrolithiasis may be associated with lower bone mineral density in men. The importance of these associations for osteoporosis case finding and management require further and prospective studies.

Arbillaga HO, Montgomery GP, Cabarrus LP, Watson MM, Martin L, Edworthy SM. · Department of Medicine, University of Calgary, Calgary, Alberta, Canada. · BMC Musculoskelet Disord. · Pubmed #11980582 links to  free full text

Abstract: BACKGROUND: The objective of the study is to examine the reliability of erosion and joint space narrowing scores derived from hand x-rays posted on the Internet compared to scores derived from original plain x-rays. METHODS: Left and right x-rays of the hands of 36 patients were first digitized and then posted in standard fashion to a secure Internet website. Both the plain and Internet x-rays were scored for erosions and joint space narrowing using the Sharp/Genant method. All scoring was completed in a blind and randomized manner. Agreement between plain and Internet x-ray scores was calculated using Lin's concordance correlations and Bland-Altman graphical representation. RESULTS: Erosion scores for plain x-rays showed almost perfect concordance with x-rays read on the Internet (concordance 0.887). However, joint space narrowing scores were only "fair" (concordance 0.365). Global scores demonstrated substantial concordance between plain and Internet readings (concordance 0.769). Hand x-rays with less disease involvement showed a tendency to be scored higher on the Internet versions than those with greater disease involvement. This was primarily evident in the joint space narrowing scores. CONCLUSIONS: The Internet represents a valid medium for displaying and scoring hand x-rays of patients with RA. Higher scores from the Internet version may be related to better viewing conditions on the computer screen relative to the plain x-ray viewing, which did not include magnifying lens or bright light. The capability to view high quality x-rays on the Internet has the potential to facilitate information sharing, education, and encourage collaborative studies.

Fritzler MJ, Hanson C, Miller J, Eystathioy T. · McCaig Center for Joint Injury and Arthritis Research, Faculty of Medicine, University of Calgary, Alberta, Canada. · J Clin Lab Anal. · Pubmed #11948800 No free full text.

Abstract: The objective of this study was to analyze apparently discrepant results that arose during the use of an indirect immunofluorescence (IIF) assay using transfected HEp-2 cells to detect anti-SS-A/Ro autoantibodies in human sera. Fourteen sera that had SS-A/Ro antibodies as detected on this commercial substrate, but did not have antibodies to SS-A/Ro as determined by double immunodiffusion (ID) or enzyme-linked immunosorbent assay (ELISA), were studied by immunoprecipitation (IP) of radiolabeled cell extracts and full-length recombinant SS-A/Ro. A multi-antigen strip immunoblotting (IB) assay containing both the 52- and 60-kDa antigens was included in the analysis. We confirmed that 12 of 14 of the sera under study had antibodies to SS-A/Ro protein antigens as determined by at least one other immunoassay. One serum had antibodies to hyRNA but no detectable reactivity with the 52- or 60-kDa antigens. One serum remained negative in all assays for SS-A/Ro autoantibodies.

Hart DA, Reno C. · McCaig Centre for Joint Injury and Arthritis Research, Faculty of Medicine, University of Calgary, Alberta, Canada. · J Rheumatol. · Pubmed #10451077 No free full text.

Abstract: OBJECTIVE: To determine whether pregnancy leads to changes in mRNA levels for molecules in normal synovium in an experimental model. METHODS: Total RNA was isolated from synovium of primigravida adolescent and skeletally mature rabbits, multiparous adult rabbits, and age matched controls. mRNA levels for cytokines, COX-2, iNOS, growth factors, proteinases and inhibitors, and matrix molecules were assessed by semiquantitative reverse transcription polymerase chain reaction. RESULTS: Pregnancy led to significant alterations in mRNA levels for 14/17, 6/17, and 5/17 genes in the 3 pregnant groups, respectively, compared to their controls. The only mRNA levels significantly depressed in all 3 groups were for collagen I and III, a finding consistent with a role for relaxin in the observed changes. CONCLUSION: Pregnancy can affect the molecular biology of the normal synovium and thus pregnancy associated hormones such as relaxin may also affect the inflamed synovium. The effect of relaxin in models of rheumatoid arthritis should be evaluated.