PubMed Health⌕ Search

Biomedical subjects

Derek L Mattey

Publications and source records attributed to Derek L Mattey.

15 recordsLinked to original sources
PubMed2005

Polymorphism in the tumour necrosis factor receptor II gene is associated with circulating levels of soluble tumour necrosis factor receptors in rheumatoid arthritis.

Levels of soluble tumour necrosis factor receptors (sTNFRs) are elevated in the circulation of patients with rheumatoid arthritis (RA). Although these receptors can act as natural inhibitors of tumour necrosis factor-alpha, levels of sTNFRs in RA appear to be insufficient to prevent tumour necrosis factor-alpha induced inflammation. The factors that regulate circulating levels of sTNFRs are unclear, but polymorphisms in the tumour necrosis factor receptor genes may play a role. We investigated the relationship between polymorphisms in the tumour necrosis factor receptor I (TNF-RI) and II (TNF-RII) genes and levels of sTNFRs in two groups of Caucasian RA patients: one with early (disease duration < or = 2 years; n = 103) and one with established disease (disease duration > or = 5 years; n = 151). PCR restriction fragment length polymorphism analysis was used to genotype patients for the A36G polymorphism in the TNF-RI gene and the T676G polymorphism in TNF-RII. Levels of sTNFRs were measured using ELISA. We also isolated T cells from peripheral blood of 58 patients with established RA with known TNF-R genotypes, and release of sTNFRs into the culture medium was measured in cells incubated with or without phytohaemagglutinin. Serum levels of the two sTNFRs (sTNF-RI and sTNF-RII) were positively correlated in both populations, and the level of each sTNFR was significantly higher in the patients with established disease (P < 0.0001). Multiple regression analyses corrected for age, sex and disease duration revealed a significant trend toward decreasing sTNF-RI and sTNF-RII levels across the TNF-RII genotypes (TT > TG > GG) of patients with established disease (P for trend = 0.01 and P for trend = 0.03, respectively). A similar nonsignificant trend was seen for early disease. No relationship with the TNF-RI A36G polymorphism was observed. sTNFRs released by isolated T cells exhibited a similar trend toward decreasing levels according to TNF-RII genotype, although only the association with levels of sTNF-RII was significant. Strong correlations were found between levels of circulating sTNFRs and levels released by T cells in vitro. Our data indicate that the T676G polymorphism in TNF-RII is associated with levels of sTNFRs released from peripheral blood T cells, and with circulating levels of sTNFR in patients with RA.

Arthritis, Rheumatoid↗
PubMed2005

Anemia in rheumatoid arthritis: association with polymorphism in the tumor necrosis factor receptor I and II genes.

OBJECTIVE: To investigate whether polymorphisms in the tumor necrosis factor receptor I (TNFRSF1A) and receptor II (TNFRSF1B) genes are associated with the anemia observed in rheumatoid arthritis (RA). METHODS: We studied a group of Caucasian patients (n = 160) with established RA on whom longitudinal data of hemoglobin (Hb) levels over 5 years were recorded. A second group of patients (n = 102) with early RA was used for a confirmation study. Polymerase chain reaction restriction fragment length polymorphism analysis was used to genotype patients for the A36G polymorphism in the TNFRSF1A gene, and the T676G polymorphism in TNFRSF1B. Serum levels of ferritin were determined by ELISA and used to differentiate between iron deficiency anemia (IDA) and anemia of chronic disease (ACD). Data were analyzed by Kruskal-Wallis analysis of variance and logistic regression analysis. RESULTS: The TNFRSF1A GG genotype was associated with lower 5-year mean area under the curve Hb levels compared with other genotypes (p = 0.01). Analysis of anemic status showed an increased frequency of anemia in patients carrying a G allele, with the highest frequency in GG homozygotes. The TNFRSF1A GG genotype was significantly associated with IDA in established RA (OR 4.3, p = 0.01), and this was confirmed in a group of patients with early RA (OR 4.8, p = 0.04). Analysis of the combined groups also showed a weak association of the G allele with ACD (OR 2.2, p = 0.04). No association was found between TNFRSF1B variants and anemia when the cohorts were analyzed separately, but an association between carriage of the T allele and ACD was found when the 2 groups were combined (OR 11.5, p = 0.01). CONCLUSION: Our data suggest that polymorphisms within the TNFRSF1A and TNFRSF1B genes are associated with IDA and/or ACD in patients with RA.

Age Distribution↗
PubMed2004

Circulating cytokines and chemokines in acute symptomatic parvovirus B19 infection: negative association between levels of pro-inflammatory cytokines and development of B19-associated arthritis.

The aim of the study was to characterise the profile and clinical correlates (arthritis, rash, and fatigue) of cytokines, chemokines, and other mediators in symptomatic acute parvovirus B19 infection. Serum was examined from cases of acute B19 infection (as defined by serum anti-B19 IgM positivity) (n = 84), and in normal persons (n = 43) for B19 markers (serum B19 antibodies and DNA), rheumatoid factor (RF), and antinuclear antibody (ANA). A panel of cytokines/chemokines was measured in duplicate using the Bioplex Protein Array system (BioRad Hemel Hempstead, UK). These included interleukin-1 beta (IL-1 beta), IL-4, IL-5, IL-6, IL-8, IL-13, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), macrophage chemoattractant protein-1 (MCP-1), granulocyte-monocyte colony stimulating factor (GM-CSF), transforming growth factor-beta1 (TGF-beta 1), endothelin-1 (ET-1), and neopterin. Acute symptomatic infection was characterised by specific IgG positivity (83%), serum B19 DNA positivity (96%), and raised levels of IL-4, IL-6, IL-8, TNF-alpha, IFN-gamma, MCP-1, GM-CSF, TGF-beta 1, and ET-1. Patients with acute B19-associated arthritis were found to have lower levels of IL-6, TNF-alpha, and GM-CSF than patients without arthritis, while those with rash had lower levels of TGF-beta 1. It is concluded that cytokine levels following acute symptomatic infection with parvovirus B19 indicate a state of immune activation. The profile of circulating mediators may provide insights into the possible pathogenesis of particular clinical manifestations of this infection.

Adolescent↗
PubMed2004

Can gold therapy be used more safely in rheumatoid arthritis? Adverse drug reactions are more likely in patients with nodular disease, independent of HLA-DR3 status.

OBJECTIVE: . To investigate whether features associated with severe rheumatoid arthritis (RA) are predictive of adverse drug reactions (ADR) to gold salts, independent of HLA-DR3 status. METHODS: A cohort of patients with RA (n = 41) who developed thrombocytopenia (platelets < 100 10(6)/l) or proteinuria (> 1.0 g/24 h) upon treatment with gold sodium thiomalate was identified from patient records and matched for age, sex, and disease duration with 41 RA controls treated with gold without development of ADR. A second group of 161 random RA patients that had received gold therapy for at least as long without development of an ADR was also compared. All patients were typed for HLA-DRB1, and the presence of rheumatoid factor (RF), antinuclear antibodies (ANA), and nodules before initiation of therapy was recorded. Association of clinical or genetic factors with ADR was investigated using the McNemar test and logistic regression analysis. RESULTS: Patients with ADR were more likely to have nodular disease than their matched controls (51.3% vs 25.6%; odds ratio, OR = 3.0, p = 0.02) and more likely to be HLA-DR3 positive (41.2% vs 17.6%; OR = 3.0, p = 0.045). No difference between the groups was found for RF or ANA. Nodular disease was associated with development of ADR independently of HLA-DR3, although a combination of both factors significantly increased the likelihood of an ADR. CONCLUSION: Our data suggest that nodular disease may be a predictor of gold-induced ADR independent of HLA-DR3.

Adult↗
PubMed2003

HLA-DRB1 status affects endothelial function in treated patients with rheumatoid arthritis.

PURPOSE: To examine endothelial function in rheumatoid arthritis patients and to assess whether clinical or genetic factors affect the development of endothelial dysfunction. METHODS: Fifty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with one or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, or cardiovascular disease were excluded. Thirty-one age-, sex-, and ethnically matched controls were also studied. Endothelium-dependent (postischemia) and -independent (postnitroglycerin) vasodilatation were measured by brachial ultrasonography. Patients were genotyped for human leukocyte antigen (HLA)-DRB1. RESULTS: Patients had decreased endothelium-dependent vasodilatation (mean [+/- SD], 3.8% +/- 4.9%) compared with controls (8.0% +/- 4.5%; P <0.001). There were no differences in endothelium-independent vasodilatation. Clinical features were not associated with endothelial dysfunction. Endothelium-dependent vasodilatation was lower in the 30 rheumatoid arthritis patients with the HLA-DRB1*04 shared epitope alleles (2.4% +/- 4.1%) than in the remaining patients (5.5% +/- 5.3%; P = 0.01). Similar results were seen for patients with the HLA-DRB1*0404 shared epitope allele (-0.4% +/- 2.5%) compared with other patients (4.4% +/- 4.9%; P = 0.01). CONCLUSION: Patients with chronically treated rheumatoid arthritis had evidence of endothelial dysfunction, especially those with certain HLA-DRB1 genotypes. If confirmed, our results suggest that HLA-DRB1 status may be a predictor of cardiovascular risk in these patients.

Adult↗
PubMed2003

No association of polymorphisms in the tumor necrosis factor receptor I and receptor II genes with disease severity in rheumatoid arthritis.

OBJECTIVE: A recent Italian study found that homozygosity for the G allele of the +196 single nucleotide polymorphism (SNP) of the tumor necrosis factor receptor II (TNFRSF1B) gene was more prevalent in patients with severe rheumatoid arthritis (RA). We investigated whether this particular SNP, and also one at position +36 in exon 1 of the TNF receptor I (TNFRSF1A) gene, are associated with disease severity. METHODS: A group of 181 Caucasian patients with RA was studied. DNA was isolated from patient blood samples and subsequently used to genotype both the exon 1 TNFRSF1A SNP and the exon 6 TNFRSF1B SNP by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Radiographic damage was measured by the Larsen score, and functional outcome was assessed by the Health Assessment Questionnaire (HAQ). Data were analyzed by multiple regression analysis, with correction for age, sex, and disease duration. RESULTS: The mean Larsen and HAQ scores did not differ significantly between each of the genotypes from the 2 TNFR SNP. No significant associations between the +36 TNFRSF1A SNP or the +196 TNFRSF1B SNP genotypes and disease severity were found after correcting for age, sex, and disease duration. CONCLUSION: Our data suggest that neither the +36 TNFRSF1A SNP nor the +196 TNFRSF1B SNP is associated with RA severity in a population of Caucasian patients with RA.

Antigens, CD↗
PubMed2002

Association of symptomatic acute human parvovirus B19 infection with human leukocyte antigen class I and II alleles.

To determine the effect of the major histocompatibility complex on the development of symptoms during acute human parvovirus B19 infection, we compared human leukocyte antigen (HLA) class I and II alleles in 36 patients with symptomatic acute B19 infection with those in >900 control subjects from northwestern England. The frequency of each of HLA-DRB1*01 (P=.016), DRB1*04 (P=.007), and DRB1*07 (P<.0001) alleles was significantly higher in parvovirus B19 patients than in control subjects. In the parvovirus group, 63.9% carried the rheumatoid arthritis-associated shared epitope sequence, compared with 45% of control subjects (odds ratio [OR], 2.2; 95% confidence interval [CI], 0.97-4.8; P=.04), and carriage was associated with fatigue during the acute phase (OR, 4.2; 95% CI, 0.8-23.9; P=.047). All symptomatic parvovirus-associated HLA-DRB1 molecules carry a neutrally charged glutamine at position 10 and a positively charged lysine at position 12 of the first hypervariable region. HLA-B49 was associated with parvovirus infection independently of HLA-DRB1*01, DRB1*04, and DRB1*07.

Acute Disease↗
PubMed2002

Smoking and disease severity in rheumatoid arthritis: association with polymorphism at the glutathione S-transferase M1 locus.

OBJECTIVE: To determine whether the relationship between smoking and disease severity in women with rheumatoid arthritis (RA) is associated with polymorphism at the glutathione S-transferase (GST) M1 locus. METHODS: Genotyping for GSTM1 was carried out using polymerase chain reaction methodology on 164 women with established RA. Smoking history was obtained on each patient. Radiographic damage was measured by the Larsen score, and functional outcome was assessed by the Health Assessment Questionnaire (HAQ). Data were analyzed by multiple regression analyses, with correction for age and disease duration. RESULTS: Ever having smoked was associated with a worse radiographic and functional outcome than was never having smoked. Both past and current smoking were associated with increased disease severity. Stratification by GSTM1 status revealed that polymorphism at this locus affected the relationship between smoking and disease outcome measures. Patients who lacked the GSTM1 gene and had ever smoked had significantly higher Larsen and HAQ scores than did those who lacked the gene and had never smoked. Radiographic outcome in these patients was worse than that in patients who had the GSTM1 gene and who had smoked. The associations were not affected by correction for socioeconomic status. Rheumatoid factor (RF) production was found to be associated with smoking in only the GSTM1-null patients. CONCLUSION: Our data suggest that disease outcome in female RA patients with a history of smoking is significantly worse than in those who have never smoked. Smoking was associated with the most severe disease in patients who carried the GSTM1-null polymorphism. This association may be due in part to a relationship between the GSTM1 polymorphism and RF production in smokers.

Adult↗
PubMed2002

Relationship among the HLA-DRB1 shared epitope, smoking, and rheumatoid factor production in rheumatoid arthritis.

OBJECTIVE: Rheumatoid factor (RF) production in rheumatoid arthritis (RA) is generally associated with more severe disease. In some studies, RF production has been associated with carriage of HLA-DRB1 alleles encoding the RA-associated shared epitope (SE). Patients who smoke are also more likely to be RF positive. In this study, we investigated whether the association between RF production and smoking was influenced by carriage of the SE. METHODS: The smoking histories of 371 RA patients attending a hospital clinic were recorded. RF levels and SE status were determined for every patient, and the associations between the SE, smoking, and RF production were examined. HLA-DRB1 typing was performed using polymerase chain reaction. Results were analyzed using chi-square tests and logistic regression analysis. RESULTS: Patients who had ever smoked were significantly more likely to be RF positive than nonsmokers (odds ratio 2.2, P < 0.0001). This remained significant (P = 0.003) after correction for age, sex, and disease duration in a logistic regression model. An association was also found between RF positivity and carriage of the SE (P = 0.03, after correction for age, sex, and disease duration), but significance was reduced or lost after correction for previous or current smoking (P = 0.05 and 0.09, respectively). Examination of the major SE phenotypes in this RA population by multivariate logistic regression analysis revealed that only DRB1*0401 was associated with RF positivity, and that this was independent of the influence of smoking. CONCLUSION: Our data confirm that RF production in RA patients is associated with smoking. This does not appear to depend on an HLA-DR-restricted immune response. The association of the SE with RF positivity is primarily due to HLA-DRB1*0401. This appears to be independent of the association with smoking, although smoking further increases the likelihood of RF production in DRB1*0401 patients.

Adult↗
PubMed2002

Patients chosen for treatment with cyclosporine because of severe rheumatoid arthritis are more likely to carry HLA-DRB1 shared epitope alleles, and have earlier disease onset.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) selected for treatment with cyclosporin A (CSA) because of severe disease are more likely to carry HLA-DRB1 alleles encoding the conserved "shared epitope" (SE) sequence. METHODS: The majority of patients (n = 178) were currently being treated with methotrexate (MTX), either alone or in combination with chloroquine and/or CSA. In about 30% of patients, treatment with CSA had been initiated because of limited response to MTX or MTX and chloroquine. Patients were treated as clinically indicated without knowledge of their HLA-DRB1 status. HLA-DRB1 typing was by a reverse dot blot method. RESULTS: Patients that had been treated with CSA were significantly more likely to carry an SE allele than patients not treated with CSA (81.5% vs 60.5%; OR 2.9, p = 0.006). Patients with 2 SE alleles were the most likely to have been treated with CSA. Results were still significant after correction for age, sex, and disease duration in a logistic regression model. There was no association between rheumatoid factor positivity and requirement for CSA therapy. Examination of individual SE alleles by multiple logistic regression analysis indicated that the strongest association was with presence of HLA-DRB1**0401 (p = 0.004). The DRB1*0401/*0404 genotype provided the greatest risk of requiring CSA treatment. Patients selected for CSA treatment had developed RA at a significantly earlier age than those not requiring CSA (44.4 vs 51.3 yrs; p = 0.004). CONCLUSION: Patients requiring treatment with CSA because of severe RA were significantly more likely to carry an SE allele than patients not requiring such treatment. CSA treated patients were also more likely to have had earlier age of disease onset. These data provide further evidence that bearing the SE (particularly 2 alleles) is associated with development of severe RA.

Adult↗
PubMed2002

Intercellular adhesion molecule-1 gene polymorphisms in isolated polymyalgia rheumatica.

OBJECTIVE: In untreated polymyalgia rheumatica (PMR), high levels of circulating soluble intercellular adhesion molecule-1 (ICAM-1) have been observed. To investigate the clinical implication of ICAM-1 polymorphisms in isolated PMR, we examined their potential influence in an unselected series of patients. METHODS: We studied 72 patients with isolated PMR and 129 ethnically matched controls from Lugo, Spain. Patients and controls were genotyped for HLA-DRB1 and ICAM-1 polymorphism at codons 241 and 469 by molecular methods. RESULTS: The distribution of alleles and genotypes for each ICAM-1 polymorphism did not show significant differences between patients with isolated PMR and controls. There were also no associations between ICAM-1 polymorphisms and relapses of the disease. The latter was primarily associated with carriage of an HLA-DRB1*0401 allele (OR 7.2, p = 0.01), although all relapsed patients with HLA-DRB1*0401 also carried the GG genotype of the ICAM-1 polymorphism at codon 241. The presence of both HLA-DRB1*0401 and the GG241 ICAM-1 genotype gave an OR of 15.2 (p = 0.005) after correction for age and sex. CONCLUSION: Although ICAM-1 polymorphisms alone do not appear to be associated with disease severity in isolated PMR, the presence of both HLA-DRB1*0401 and the ICAM-1 codon 241 GG homozygosity was significantly associated with increased risk of relapses in these patients.

Gene Frequency↗
PubMed2002

Chronic fatigue syndrome and arthralgia following parvovirus B19 infection.

OBJECTIVE: To determine the incidence of arthralgia and fatigue complicating B19 infection, along with associated B19 markers and autoantibodies. METHODS: We studied patients with acute B19 infection (n = 51), patients followed from the time of acute B19 infection (mean 22.5 mo) (n = 39), and healthy controls (n = 50). Clinical details were collected using a questionnaire and blood was tested for B19 markers and autoantibodies. RESULTS: Acute B19 arthralgia occurred in 31 patients and was associated with female sex (p = 0.007) and age > 20 years (p = 0.02). Acute B19 fatigue occurred in 8 patients and was not significantly associated with any marker. At followup, symptoms consisted of arthralgia (n = 5), arthralgia and fatigue (n = 6), fatigue (n = 7), lymphadenopathy (n = 1), and purpura due to thrombocytopenia (n = 2). Chronic B19 arthralgia was associated with persistent B19 viremia (p = 0.029). Comparison of the B19 followup group with the controls revealed a significantly increased prevalence of arthralgia (p = 0.0002), fatigue (p < 0.0001), and all other markers. Chronic B19 arthralgia was associated with both acute B19 arthralgia (p = 0.0168) and positive ANA at acute infection (p = 0.0043). Chronic B19 fatigue was associated with acute B19 fatigue (p = 0.011). Five patients fulfilled the Centers for Disease Control criteria for a diagnosis of chronic fatigue syndrome (CFS) and one of these was negative for serum anti-B19 IgG at followup by both Western blot and immunofluorescence. However, there was no characteristic pattern of B19 markers/autoantibodies in patients with B19 associated chronic fatigue. CONCLUSION: CFS may follow acute parvovirus B19 infection; however, attribution of a case of CFS to B19 infection may be extremely difficult in the absence of serological confirmation of acute infection at fatigue onset.

Adult↗
PubMed2002

Nodular disease in rheumatoid arthritis: association with cigarette smoking and HLA-DRB1/TNF gene interaction.

OBJECTIVE: To investigate the association of nodular disease in rheumatoid arthritis (RA) with smoking, seropositivity, and polymorphisms at HLA-DRB1 and TNF loci. METHODS: Consecutive patients with RA (n = 420) attending a hospital clinic were examined for the presence of subcutaneous nodules. Rheumatoid factor (RF) status and HLA-DRB1 genotype were determined on every patient, and their smoking history was recorded. TNFa microsatellite polymorphisms were examined in a subgroup of 144 patients. The relationships between smoking, RF status, HLA-DRB1 genotype, TNFa microsatellite polymorphism, and the presence of nodules were examined using chi-square tests and logistic regression analyses. RESULTS: Current smokers were more likely to have nodular disease than those who had never smoked (OR 1.8, 95% CI 1.0-2.9). An association was also found between RF positivity and nodular disease (OR 2.2, 95% CI 1.2-3.8) that remained significant after correction for current smoking. A combination of current smoking and seropositivity increased the risk of nodular disease (OR 3.9, 95% CI 1.7-9.1). Analysis of HLA-DRB1 genotypes in this RA population revealed that only DRB1*0401 homozygotes were associated with nodular disease, and that this was independent of the influence of smoking and seropositivity. Individual TNFa microsatellite alleles were not associated with the presence of nodules, but an interactive effect was found between the TNF a6 allele and homozygosity for DRB1*0401. CONCLUSION: Our data indicate that nodular disease in RA is independently associated with current cigarette smoking, seropositivity, and homozygosity for HLA-DRB1*0401. The latter association involves a possible interaction with the TNF a6 microsatellite allele.

Adult↗
PubMed2001

Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue.

To investigate whether cytokine responses may have a bearing on the symptoms and outcome of parvovirus B19 infection, circulating cytokines were measured during acute infection (n=51), follow-up of acute infection (n=39) and in normal healthy controls (n=50). At acute B19 virus infection (serum anti-B19 IgM-positive), patients ranged in age from 4 to 54 years, with a mean age of 28.2 years. The male:female ratio was 1:4.1 and symptoms were rash (n=15), arthralgia (n=31), fatigue (n=8), lymphadenopathy (n=4), foetal hydrops (n=3), transient aplastic crisis (n=2), neutropenia (n=2), myelodysplasia (n=1), thrombocytopenia (n=1) and pancytopenia (n=1). Of these patients, 39 were contacted after a follow-up period of 2-37 months (mean of 22.5 months). In comparison with normal controls, detectable IL-6 was associated with acute B19 virus infection (26%; P=0.0003), but not with follow-up (6%; P=0.16). Detection of interferon (IFN)-gamma was associated with acute B19 virus infection (67%; P<0.0001) and follow-up (67%; P<0.0001). Detection of tumour necrosis factor (TNF)-alpha was associated with acute B19 virus infection (49%; P<0.0001) and follow-up (56%; P<0.0001). IL-1beta was detected in acute infection (20%), but not at follow-up. At acute B19 virus infection, detection of serum/plasma IL-6 was associated with rheumatoid factor (P=0.038) and IFN-gamma (> or =7 pg/ml) was associated with fatigue in those patients of > or =15 years of age (P=0.022). At follow-up, fatigue was associated with IFN-gamma (> or =7 pg/ml) and/or TNF-alpha (> or =40 pg/ml) (P=0.0275). Prolonged upregulation of serum IFN-gamma and TNF-alpha appears to represent a consistent host response to symptomatic B19 virus infection.

Acute Disease↗