Rheumatoid Arthritis: Rahman P

Rahman P, Greenwood C. · No affiliation provided · J Rheumatol. · Pubmed #15940752 links to  free full text

This publication has no abstract.

O'Rielly DD, Roslin NM, Beyene J, Pope A, Rahman P. · Department of Rheumatology, Memorial University of Newfoundland, Newfoundland, Canada. · Pharmacogenomics J. · Pubmed #19365401 No free full text.

Abstract: Although tumor necrosis factor-alpha (TNF-alpha) blockade is a very effective therapy for rheumatoid arthritis (RA), not all patients achieve a favorable outcome. The objective of this study was to determine if the common TNF-alpha variant -308(A) predicts poor response to TNF-alpha inhibitors in RA patients using meta-analysis. Studies were identified using MEDLINE and EMBASE. Data were extracted based on DAS28 or achieving at least American College of Rheumatology 20 response. A total of nine studies met the inclusion criteria representing a total of 692 RA patients. There was no significant heterogeneity among study effect sizes (P=0.36). The frequency of the A allele was 22% (119/531) in responders and 37% (60/161) in non-responders. The odds of having the A allele was lower in responders versus non-responders (odds ratio (OR)=0.43, 95% confidence intervals (CI): 0.28-0.68, P=0.000245), irrespective of the TNF-alpha inhibitor prescribed, indicating that the -308(A) variant predicts poor response to TNF-alpha inhibitors. The clinical utility of prospectively genotyping for this variant when initiating anti-TNF-alpha therapy for RA should now be formally assessed.

Russell A, Beresniak A, Bessette L, Haraoui B, Rahman P, Thorne C, Maclean R, Dupont D. · University of Alberta, Edmonton, Canada. · Clin Rheumatol. · Pubmed #19089488 No free full text.

Abstract: To assess the cost-effectiveness of abatacept compared to different biologic treatment strategies for moderate to severe rheumatoid arthritis based on current medical practices in Canada. A model was constructed to assess the cost-effectiveness of various biologic treatments over a 2-year time horizon, using two effectiveness endpoints: "low disease activity state" (LDAS) and "remission". Abatacept, as first biologic agent after an inadequate response to DMARDs, provides greater treatment success rate for achieving LDAS (29.4% versus 15.6%) and remission (14.8% versus 5.2%), and appears significantly more cost-effective compared to the sequential use of anti-TNF agents (p<0.001). Abatacept, as second biologic agent after an inadequate response to one anti-TNF agent, provides greater treatment success rate for achieving LDAS (17.1% versus 10.2%) and remission (7.4% versus 3.9%) and appears significantly more cost-effective compared to the sequential use of anti-TNF agents (p<0.001). Abatacept is a cost-effective strategy in patients with an inadequate response to DMARDs or to one anti-TNF agent.

Heale CE, Fåhraeus-Van Ree GE, Rahman P, Richardson VJ. · Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada. · J Histochem Cytochem. · Pubmed #17242466 links to  free full text

Abstract: Rheumatoid arthritis (RA) is a relatively common autoimmune disease with strong genetic and environmental determinants. The disease manifests itself as inflammation of the synovia and usually progresses to joint erosion and destruction. The disease can also be considered as a systemic disease because extra-articular manifestations are often observed throughout many organs and tissues of the body. Patients with severe RA have altered peripheral blood monocytes (PBM) that express activation markers. Two such markers, PKC-eta and iNOS, were studied using confocal laser scanning microscopy to determine how these markers are expressed during disease progression. Healthy individuals expressed neither of the two markers, but there was an elevated level of PKC-eta observed as the disease progressed (40% in mild RA and 100% in severe RA patients). Concordant expression of the two markers was observed in only 3% of PBM from mild RA patients, reaching 38% in severe RA patients. No cells expressing iNOS alone were observed in any of the patients studied. These data support the hypothesis linking PKC-eta expression with the regulation and predisposition to the development of the iNOS phenotype in severe RA patients. PKC-eta may therefore be a key regulator in the production of elevated plasma nitric oxide (NO) and corresponding circulating reactive nitrogen intermediates in severe RA and may be a possible target to regulate iNOS induction and NO production by monocytic cells in RA patients and possibly other inflammatory diseases.

Butt C, Lim S, Greenwood C, Rahman P. · Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada. <> · BMC Musculoskelet Disord. · Pubmed #17204151 links to  free full text

Abstract: BACKGROUND: Angiogenesis appears to be a first-order event in psoriatic arthritis (PsA). Among angiogenic factors, the cytokines vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and fibroblast growth factors 1 and 2 (FGF1 and FGF2) play a central role in the initiation of angiogenesis. Most of these cytokines have been shown to be upregulated in or associated with psoriasis, rheumatoid arthritis (RA) or ankylosing spondylitis (AS). As these diseases share common susceptibility associations with PsA, investigation of these angiogenic factors is warranted. METHODS: Two hundred and fifty-eight patients with PsA and 154 ethnically matched controls were genotyped using a Sequenom chip-based MALDI-TOF mass spectrometry platform. Four SNPs in the VEGF gene, three SNPs in the EGF gene and one SNP each in FGF1 and FGF2 genes were evaluated. Statistical analysis was performed using Fisher's exact test, and the Cochrane-Armitage trend test. Associations with haplotypes were estimated by using weighted logistic models, where the individual haplotype estimates were obtained using Phase v2.1. RESULTS: We have observed an increased frequency in the T allele of VEGF +936 (rs3025039) in control subjects when compared to our PsA patients [Fisher's exact p-value = 0.042; OR 0.653 (95% CI: 0.434, 0.982)]. Haplotyping of markers revealed no significant associations. CONCLUSION: The T allele of VEGF in +936 may act as a protective allele in the development of PsA. Further studies regarding the role of pro-angiogenic markers in PsA are warranted.

Butt C, Peddle L, Greenwood C, Hamilton S, Gladman D, Rahman P. · Memorial University of Newfoundland, Hospital for Sick Children, Department of Public Health Sciences, University of Toronto, Toronto, Canada. · Arthritis Res Ther. · Pubmed #16507123 links to  free full text

Abstract: Recent studies have implicated PTPN22 and tp53 in susceptibility to several autoimmune diseases, including rheumatoid arthritis, suggesting that these genes are important in maintaining immune homeostasis. Because autoimmune diseases may share similar susceptibility loci, investigation of these genes in psoriatic arthritis (PsA) is of potential relevance. As a result we investigated known coding polymorphisms in PTPN22 and tp53 in a homogenous Caucasian PsA cohort from Newfoundland, Canada and an admixed Caucasian PsA cohort from Toronto, Canada. We observed a moderate association of the R620W variant of PTPN22 with PsA in the Toronto population only. Because of the conflicting findings reported regarding the association of PTPN22 with PsA, further studies in other PsA populations are warranted.

Pham TN, Rahman P, Tobin YM, Khraishi MM, Hamilton SF, Alderdice C, Richardson VJ. · Faculty of Medicine, Memorial University of Newfoundland and Rheumatology Research, St. Clare's Mercy Hospital, St. John's, Newfoundland A1B 3V6, Canada. · J Rheumatol. · Pubmed #14719189 No free full text.

Abstract: OBJECTIVE: To quantify circulating nitric oxide (NO) levels and inducible NO synthase (iNOS) expression in peripheral blood monocyte-derived macrophages (PB-MDM) from patients with inflammatory arthritis (IA) as a measure of disease activity, and to determine if there is a correlation between expression of iNOS and protein kinase C-eta (PKC-eta). METHODS: PB-MDM were isolated from whole blood of 20 patients with IA (14 rheumatoid arthritis and 6 peripheral spondyloarthropathies). Thirteen patients with osteoarthritis (OA) and 9 healthy individuals were controls. Serum NO levels were measured by indirect determination of nitrite and nitrate. Expression of PKC-eta and iNOS was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. RESULTS: Serum NO (189.9 +/- 49.7 microM) was significantly higher (p < 0.0028) in IA patients than in controls (131.1 +/- 18.5 microM) or patients with OA (126.9 +/- 37.1 microM). IA patients with severe inflammation had highest levels of NO, while those with mild inflammation had normal levels of NO. RT-PCR showed that PB-MDM from IA patients with active disease co-expressed iNOS and PKC-eta. This was observed in 15 out of 16 cases. All other groups with normal plasma NO expressed neither gene. CONCLUSION: Our findings show that elevated plasma NO levels were only present in IA patients with severe disease activity. We show for the first time a positive correlation between PKC-eta and iNOS expression in arthritis, supporting our earlier in vitro findings that PKC-eta expression was essential for lipopolysaccharide-mediated iNOS induction and NO production in human monocytes. PKC-eta may be important for the development of IA-induced iNOS positive phenotype in human PB-MDM.

Gladman DD, Farewell VT, Rahman P, Schentag CT, Pellett F, Ng CM, Wade JA. · University of Toronto, Toronto, Canada. · Hum Immunol. · Pubmed #11704286 No free full text.

Abstract: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor. An increased frequency of HLA-DR4 has been noted in PsA, particularly among patients with a rheumatoid arthritis like (RA) arthritis. The aim of the current investigation was to compare HLA-DRB1*04 alleles in patients with PsA, patients with RA, and healthy controls. Sample size calculations based on the frequency of HLA-DR4 suggested that 90 individuals in each patient group would be sufficient to address our question. Therefore, 90 HLA-DRB1*04 positive patients from each patient group underwent high resolution molecular typing and were included in this study. Although HLA-DRB1*0401 was the most frequent allele in all groups, its frequency among the PsA patients was lower than that of RA patients and controls. HLA-DRB1*0402 was higher among patients with PsA. Patients with RA were more likely to have more than one shared epitope allele than either PsA or the healthy control group. HLA-DQB1 alleles did not contribute further information. We suggest that the differences in the class II HLA epitope(s) may also be related to interaction specificity with another molecule functioning in the immune response to a putative arthritogenic antigen and result in differences in disease expression.

Rahman P, Nguyen E, Cheung C, Schentag CT, Gladman DD. · University of Toronto Psoriatic Arthritis Clinic, University of Toronto, Toronto Western Hospital, Ontario, Canada. · J Rheumatol. · Pubmed #11361186 No free full text.

Abstract: OBJECTIVE: To compare the radiological severity of patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Patients were identified from the University of Toronto PsA and RA databases. Using the earliest available radiographs, each RA patient was matched to a single PsA patient on the basis of sex, age, and disease duration. Two rheumatologists blinded to the patient's diagnosis scored the radiographs using the modified Steinbrocker method. RESULTS: PsA and RA groups were similar with respect to demographics as well as the use of disease modifying antirheumatic medications. No significant difference in Steinbrocker score for the hands and feet or the hands only was noted. Patients with RA had a higher radiological score in the feet. The 2 groups were similar in the number of joints with significant radiological damage (Steinbrocker 3 and 4). CONCLUSION; Overall the radiological severity in the hands and feet of patients with PsA was comparable to that of patients with RA.

Rahman P, Schentag CT, Beaton M, Gladman DD. · University of Toronto Psoriatic Arthritis Clinic, University of Toronto, Toronto Hospital, Canada. · Clin Exp Rheumatol. · Pubmed #10728438 No free full text.

Abstract: OBJECTIVE: To compare patients with familial versus sporadic psoriatic arthritis (PsA) with respect to clinical, radiological and immunogenetic features. METHODS: All patients were identified from the University of Toronto Psoriatic Arthritis Clinic. Familial and sporadic PsA were distinguished based on the proband's self-reported history. The probands were compared at presentation to clinic with respect to: demographic information, age of onset of psoriasis and inflammatory arthritis, disease activity, disease damage, laboratory variables, functional class and HLA antigens. The two groups were compared using a univariate analysis. RESULTS: In total 407 patients were included. Thirty-six patients (8.8%) were eliminated as they reported a family history of arthritis in the absence of psoriasis. Of the remaining 371 patients, 150 patients reported a positive family of either PsA or psoriasis. 221 patients (54.2%) had no family history of psoriatic arthritis, psoriasis, or "arthritis". The familial group were younger at presentation to clinic (p = 0.003), had an earlier age of onset of psoriasis (p = 0.001) and inflammatory arthritis (p = 0.001) and were more likely to be receiving treatment (p = 0.001). The mean number of actively inflamed joints was higher in the sporadic group (p = 0.035), along with a higher frequency of rheumatoid factor positivity (p = 0.04). Only the age of onset variables and medication use retained significance after correction for multiple comparisons. CONCLUSIONS: In comparing probands with familial versus sporadic PsA, we noted a marked difference in the age of onset of psoriasis and inflammatory arthritis, along with other differences in several clinical variables. These differences may be helpful in identifying PsA patients with a stronger genetic predisposition.

Paterson AD, Rahman P, Petronis A. · Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Ontario, Canada. · Hum Immunol. · Pubmed #10527397 No free full text.

Abstract: Markers near a locus for type 1 diabetes on chromosome 3q22-q25 (IDDM9) demonstrate linkage to rheumatoid arthritis, however it is not clear whether these two loci overlap. Sex-specific linkage analysis may be of interest for rheumatoid arthritis on chromosome 3q since linkage of type 1 diabetes to IDDM9 derives predominantly from affected female sibpairs, and rheumatoid arthritis is more common in females than males. Using data from a recent genome scan for rheumatoid arthritis and sex-specific linkage analysis we show that linkage of rheumatoid arthritis to chromosome 3q peaks approximately 30 cM centromeric to IDDM9. Furthermore, there is no evidence for linkage to IDDM9 in females with rheumatoid arthritis.

Rahman P, Gladman DD, Schentag CT, Petronis A. · University of Toronto, Ontario, Canada. · Arthritis Rheum. · Pubmed #10366116 links to  free full text

Abstract: OBJECTIVE: The differential expression of a disease according to the sex of the disease-transmitting parent has been demonstrated in several autoimmune disorders. The purpose of the present study was to determine whether there are differences in the transmission and expression of psoriatic arthritis (PsA) that are dependent on the sex of the affected parent. METHODS: All probands (patients with PsA) were identified from among the patients attending the University of Toronto Psoriatic Arthritis Clinic. A self-reported family history of psoriasis or PsA was noted for each proband. Differences in parental and offspring transmission with respect to the proband were evaluated. In addition, the expression of PsA according to the sex of the affected parent was assessed at the time of the proband's presentation to the clinic. RESULTS: Ninety-five probands had affected parents: 62 (65%) had an affected father, and 33 (35%) had an affected mother. Thus, the proportion of paternal transmission (0.65) was significantly greater than was expected (0.5) (P = 0.001). Twelve of 74 offspring from male probands (16.2%) were affected with psoriasis or PsA, as compared with 9 of 108 offspring from female probands (8.3%) (P = 0.10). Probands whose fathers were affected had a higher frequency of skin lesions prior to arthritis (P = 0.047), an erythrocyte sedimentation rate > 15 mm/hour (P = 0.044), and a lower incidence of rheumatoid factor (P = 0.044). No differences were noted with respect to age at the onset of psoriasis or PsA, the severity of the PsA, or the frequency of HLA antigens. CONCLUSION: There appears to be excessive paternal transmission in PsA. Further clinical confirmation and elucidation of its genetic basis is warranted.

Rahman P, Hefferton D, Robb D. · No affiliation provided · Arthritis Rheum. · Pubmed #10902777 links to  free full text

This publication has no abstract.