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W Thomson

Publications and source records attributed to W Thomson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dog MHC alleles containing the human RA shared epitope confer susceptibility to canine rheumatoid arthritis.

To determine whether canine rheumatoid arthritis (CRA) is associated with dog MHC (DLA-DRB1) alleles which contain the QRRAA/RKRAA conserved third hypervariable region (3HVR) sequence, DNA samples were extracted from 61 dogs with clinically diagnosed small-joint polyarthritis and from 425 controls. Breed-matched controls were available for 41 cases. DLA-DRB1 genotypes were identified using molecular typing methods. Phenotype frequencies were compared between cases and controls and odds ratios with 95% confidence intervals calculated. Several DLA-DRB1 alleles were associated with increased risk for CRA: DLA-DRB1*002, DRB1*009, and DRB1*018. This was also observed for the presence of any shared epitope (SE)-bearing allele. The associations with DLA-DRB1*002 and the SE were maintained when only breed-matched cases and controls were compared. This study suggests that a conserved amino acid motif in the 3HVR present in some DRB1 alleles of both dogs and humans is associated with rheumatoid arthritis in both species.

Alleles↗
PubMed2001

Mannose-binding lectin gene polymorphisms as a susceptibility factor for chronic necrotizing pulmonary aspergillosis.

It was investigated whether a deficiency of mannose-binding lectin (MBL), which binds Aspergillus species avidly in vitro, could account for chronic necrotizing pulmonary aspergillosis (CNPA), which is seen most commonly in nonimmunocompromised patients. Blood samples were obtained from 11 patients (10 white) with CNPA and were compared with blood samples from 82 white control subjects. MBL haplotype profiles were determined by polymerase chain reaction, using sequence-specific primers and sequence-specific oligonucleotide probing techniques. Seven of the 10 white patients with CNPA had MBL haplotypes that encode for low levels of the protein, compared with 25.6% of the white control subjects (P=.004). Presence of the codon 52 mutation was particularly common in patients with CNPA (P=.015), which suggests a greater involvement of this mutation.

Alleles↗
PubMed2001

Cytokine gene polymorphisms and susceptibility to juvenile idiopathic arthritis. British Paediatric Rheumatology Study Group.

OBJECTIVE: To investigate the involvement of candidate cytokine genes in the pathogenesis of juvenile idiopathic arthritis (JIA). METHODS: Single nucleotide polymorphisms and intragenic microsatellite markers within 8 candidate cytokine genes (interleukin-1alpha [IL-1alpha], IL-2, IL-4, IL-6, IL-10, interferon-alpha1 [IFNA1], interferon-gamma [IFNG], and interferon regulatory factor 1 [IRF-1]) were investigated in 417 Caucasian patients with clinically characterized JIA and a panel of 276 unrelated, healthy Caucasian controls, all from the United Kingdom. RESULTS: A novel 3'-untranslated region (3'UTR) polymorphism in IRF-1 was found to be associated with susceptibility to JIA (corrected P = 0.002). No significant association with IL-1alpha, IL-2, IL-4, IL-6, IL-10, IFNA1, or IFNG was observed. CONCLUSION: An association between JIA and a previously unreported 3'UTR polymorphism of IRF-1 was observed. This association was not found to be specific to any particular JIA subgroup. This suggests that IRF-1 may contribute to a common pathogenesis shared by all JIA patients, regardless of clinical phenotype. This is most likely to be a genetic contribution to the chronic inflammatory process that underlies JIA pathology.

3' Untranslated Regions↗
PubMed2001

Independent association of rheumatoid factor and the HLA-DRB1 shared epitope with radiographic outcome in rheumatoid arthritis.

OBJECTIVE: Findings of a recent study suggested that HLA-DRB1 alleles encoding the rheumatoid arthritis (RA) "shared epitope" (SE) were not predictive of erosive damage at 2 years in patients with early inflammatory arthritis who were rheumatoid factor (RF) positive, but were predictive in those who were RF negative. The present study was undertaken to determine whether RF status was also important in the association between the SE and radiographic outcome in patients with longstanding RA. METHODS: The association between radiographic outcome, HLA-DRBI, and RF status was examined in 299 RA patients with established disease (5-30 years). Radiographic outcome was measured by scoring radiographs of the hands and feet using the standard radiographs of Larsen. HLA-DRB1 typing was performed using polymerase chain reaction methodology. Results were stratified by RF status and analyzed by multiple regression. RESULTS: An association between radiographic severity and the SE was found in RF-, but not RF+, patients. RF- patients carrying an SE allele had higher Larsen scores than RF- patients lacking the SE, although there was no association with SE dosage. The mean Larsen score was significantly higher in RF+ patients than in RF- patients, but there were no differences between RF+ patients with 0, 1, or 2 SE alleles. Multiple regression analysis confirmed independent associations of RF and SE positivity with radiographic outcome. No significant associations were found between RF and the SE, or RF and individual SE alleles. CONCLUSION: Our data indicate that RF and the SE are independently associated with radiographic outcome in RA. In RF+ patients with longstanding RA, there is no apparent association between the presence of the SE and radiographic damage. However, in RF-patients, although radiographic outcome is generally less severe, there is an association between severity and presence of the SE.

Adult↗
PubMed2001

A novel 5'-flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic-onset juvenile idiopathic arthritis.

OBJECTIVE: To determine if polymorphisms of the macrophage migration inhibitory factor (MIF) gene are associated with systemic-onset juvenile idiopathic arthritis (JIA). METHODS: Denaturing high-performance liquid chromatography was used to screen for the MIF gene in 32 healthy Caucasian subjects. One hundred seventeen UK Caucasian patients with systemic-onset JIA and 172 unrelated healthy UK Caucasian controls were genotyped for a single-nucleotide polymorphism (SNP) identified in the 5'-flanking region of the gene, using polymerase chain reaction-restriction fragment length analysis. RESULTS: A G-to-C transition was identified at position -173 of the MIF gene. The presence of a C at -173 creates an activator protein 4 transcription factor binding site. Allele and genotype frequencies differed significantly between the patients and controls for the MIF-173 polymorphism. Individuals possessing a MIF-173*C allele have an increased risk of systemic-onset JIA (36.8% versus 20.3%) (odds ratio 2.3, 95% confidence interval 1.34-3.86; P = 0.0005). CONCLUSION: This is the first report of a SNP in the MIF gene. This polymorphism is associated with systemic-onset JIA.

5' Untranslated Regions↗
PubMed2001

Characterization of a prolactin gene polymorphism and its associations with systemic lupus erythematosus.

OBJECTIVE: Hyperprolactinemia is associated with systemic lupus erythematosus (SLE), but the mechanism is unknown. Prolactin is expressed in T lymphocytes and is under the control of an alternative promoter region. We characterized a G/T single-nucleotide polymorphism (SNP) at position -1149 of this promoter and assessed its prevalence in patients with SLE. METHODS: Electrophoretic mobility shift assays (EMSAs) were performed to determine DNA protein complex formation in the prolactin promoter. Transient transfection of reporter gene constructs containing the G/T promoter alleles into the Jurkat T cell line were used to determine transcription activity. Peripheral blood lymphocytes (PBLs) were treated in vitro with phytohemagglutinin (PHA) to determine levels of prolactin messenger RNA (mRNA). RESULTS: EMSAs indicated that binding of a GATA-related transcription factor was altered by the G/T SNP at position -1149. Transient transfection studies in Jurkat cells showed that the G allele consistently produced higher promoter activity. PHA treatment of PBLs in vitro induced a greater increment of prolactin mRNA from patients with the GG(-1149) genotype than from those with the TT(-1149) genotype. Disease association studies in a cohort of SLE patients demonstrated an increased frequency of the prolactin -1149 G allele compared with control subjects. CONCLUSION: We found a functionally significant polymorphism that alters prolactin promoter activity and mRNA levels in the lymphocytes. Altered local prolactin production by immune cells may contribute to disease progression by affecting T cell function.

Alleles↗
PubMed2001

HLA-DRB1 and disease outcome in multiple sclerosis.

The association between susceptibility to multiple sclerosis (MS) and the class II MHC allele HLA-DRB1*15 is well established although a possible relationship between this allele and outcome in MS is less clear. HLA-DRB1 typing was performed on 375 unrelated white patients with clinically definite MS and on 367 healthy controls. Putative associations of the gene with outcome were examined by dividing patients into two groups: those with an EDSS of 0-5.5 (mild/moderate disease) and those with an EDSS of 6-10 (severe disease). In order to minimise the effects of disease variability patients with a disease duration of at least 10 years or 15 years were examined. As subsidiary HLA-DRB1*03 and HLA-DRB1*04 associations have been previously reported, the effect of these alleles was also examined. As expected, HLA-DRB1*15 was found more frequently in patients than in controls (P < 0.000001). HLA-DRB1*15 positive patients had a significantly earlier age at onset than HLA-DRB1*15 negative patients. No significant associations were noted between HLA-DRB1*15 and outcome in the total patient group or in patients with a disease duration of 10 years or longer. In patients with a disease duration of at least 15 years HLA-DRB1*15 negative status was associated with a worse prognosis, although this did not remain significant after correction for multiple testing. It is thus likely that the contribution of HLA in MS is primarily towards onset and initial triggering mechanisms rather than influencing disease progression, chronicity and severity.

Adult↗
PubMed2001

Nomenclature for factors of the dog major histocompatibility system (DLA), 2000: second report of the ISAG DLA Nomenclature Committee.

The International Society for Animal Genetics (ISAG) Dog Leukocyte Antigen (DLA) Nomenclature Committee met during the "Comparative Evolution of the Mammalian major Histocompatibility Complex (MHC)" meeting in Manchester, UK on 10 September 2000. The main points discussed were the naming of class I genes and alleles, and the inclusion of alleles from other canidae.

Alleles↗
PubMed2001

Mannose binding lectin and FcgammaRIIa (CD32) polymorphism in Spanish systemic lupus erythematosus patients.

OBJECTIVE: Mannose binding lectin (MBL) and FcgammaRII (CD32) polymorphisms have both been implicated as candidate susceptibility genes in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the relationship of these polymorphisms with SLE. METHODS: We studied a cohort of 125 SLE patients from Barcelona, Spain and 138 geographically matched controls. Sequence-specific primer-polymerase chain reaction (SSP-PCR) amplification was used to determine CD32 and MBL structural polymorphisms. MBL haplotypes were established using sequence-specific oligonucleotide probing techniques. RESULTS: Patients carried the MBL codon 54 mutant allele more frequently than controls [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.2-4.0; P=0.007] and the haplotype HY W52 W54 W57 was found to be significantly lower in cases compared with controls (OR 0.6; 95% CI 0.4-0.9; P=0.016). CONCLUSION: The MBL gene codon 54 mutant allele appears to be a risk factor for SLE, whilst haplotypes encoding for high levels of MBL are protective against the disease. Differences between controls and patients were not significant when considering the FcgammaRIIa polymorphisms; similar results were observed for renal affectation.

Acute-Phase Proteins↗
PubMed2001

Seronegative rheumatoid arthritis in elderly and polymyalgia rheumatica have similar patterns of HLA association.

OBJECTIVE: To examine whether polymyalgia rheumatica (PMR) and late onset rheumatoid arthritis have identical or similar HLA-DRB1 genetic associations. METHODS: Seventy five PMR cases without evidence of giant cell arteritis were available for study. One hundred seven RA cases were investigated, of which 62 had disease onset after age 60 years. All cases were compared with 145 ethnically matched controls. All cases and controls originated from Lugo, NW Spain. HLA-DRB1 typing was performed on DNA samples using PCR based molecular methods. RESULTS: Early onset RA (< or =40 yrs) was strongly associated with DRB1*04 (DRB1*0401 and *0404). In contrast late onset RA (> or = 60 yrs) was not associated with DRB1*04 but was associated with DRB1*01. Stratification of late onset RA cases by rheumatoid factor status revealed that DRB1*01 was only increased in seropositive RA cases. Late onset seronegative RA cases exhibited increased frequency of DRB1*13/*14; this was also observed in PMR cases where coexistence of GCA had been excluded. CONCLUSION: These data indicate that (1) HLA associations with RA differ with respect to age at disease onset; and (2) seronegative late onset RA and "isolated" PMR have a similar HLA-DRB1 association and may have an identical etiological basis.

Adolescent↗
PubMed2001

HLA-DRB1 alleles encoding an aspartic acid at position 70 protect against development of rheumatoid arthritis.

OBJECTIVE: To determine whether the association between rheumatoid arthritis (RA) and HLA-DRB1 is influenced by the amino acid residue encoded at position 70 (beta70) of the third hypervariable region (HVR3) of the HLA-DRbeta chain. METHODS: The frequencies of HLA-DRB1 alleles encoding different amino acid residues at beta70 were compared between patients with RA and controls in a population from the UK and in a confirmatory population from northwestern Spain. HLA-DRB1 typing was done by polymerase chain reaction methods on 476 clinic based patients with RA and 180 healthy controls from Staffordshire and Cheshire in the UK, and on 179 clinic patients and 145 controls from Lugo, Spain. Associations were investigated using chi-square analyses and regression analyses. The extended Mantel-Haenszel procedure was used for trend analysis. RESULTS: Carriage of 2 shared epitope (SE)+ alleles encoding a glutamine at beta70 (Q70SE+/Q70SE+) was associated with the greatest risk of RA in the UK and Spanish population (odds ratios 7.93 and 4.66, respectively), while possession of 2 SE- alleles encoding an aspartic acid at beta70 (D70SE-D70SE-) was associated with the lowest risk (OR 0.23 and 0.34, respectively). In individuals carrying one SE+ allele and an accompanying D70SE- allele there was no increased risk of developing RA [OR 0.93 (UK) and 1.30 (Spain)]. Possession of D70SE- was more strongly protective than possession of Q70SE. Analysis of trend indicated that the strength of association of different DRB1 genotypes with RA could be ranked in order (from Q70SE+/Q70SE+ to D70SE-/D70SE-) according to which amino acid residues were encoded at beta70, and whether or not they formed part of a SE sequence. The severity of radiographic damage could not be ranked in the same fashion. CONCLUSION: The amino acid residue at position 70 of the HVR3 in HLA-DRbeta molecules influences susceptibility to RA. The strength of the association of DRB1 genotypes with RA is dependent not only on SE status, but also on which amino acid residues are encoded at beta70 of the DRB1 alleles. Presence of an aspartic acid residue at beta70 protects against development of RA. However, the severity of erosive damage does not appear to be associated with the amino acid substitution at 1370.

Alleles↗
PubMed2001

Polymorphism at codon 469 of the intercellular adhesion molecule-1 locus is associated with protection against severe gastrointestinal complications in Henoch-Schönlein purpura.

OBJECTIVE: Henoch-Schonlein purpura (HSP) is a small sized vasculitis affecting mainly children. Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have recently been implicated in the susceptibility to some vasculitides. To further investigate the clinical implication of ICAM-1 polymorphisms in HSP, we examined their potential association and influence in the development of severe complications in an unselected series of patients with HSP. METHODS: Fifty-two patients, of which 41 were children, were diagnosed with HSP using classification criteria of Michel, et al at the Hospital Xeral-Calde (Lugo, Spain); 129 ethnically matched controls were included. Patients had at least one year of followup. Patients and controls were genotyped by allelic oligonucleotide techniques for ICAM-I polymorphism at codon 241 and 469. RESULTS: The frequency distribution of the alleles and genotypes for each ICAM-1 polymorphism did not show significant differences between HSP patients and controls. Also, no differences between patients with or without renal manifestations were found. However, the frequency of the codon 469 K/E genotype was significantly decreased in patients without severe gastrointestinal manifestations compared to those with them (22.29 vs 65%, OR 0.1, p = 0.02, after correction for age, sex, and disease duration). None of the 11 adults exhibited the R/G genotype at codon 241 compared with 7 of 41 children (OR 0.0, 95% CI 0.0-2.9, p = 0.14). Patients with the R/G genotype were associated with low incidence of renal manifestations and none developed permanent renal involvement (renal sequelae); however, this finding did not achieve statistical significance. CONCLUSION: ICAM-1 polymorphisms alone are not associated with development of HSP, but patients not carrying the codon 469 K/E genotype are at decreased risk of developing severe gastrointestinal complications. The R/G polymorphism at codon 241 may reduce the risk of renal sequelae in the development of HSP in adulthood.

Adolescent↗
PubMed2001

HLA-DRB1*01 association with Henoch-Schönlein purpura in patients from northwest Spain.

OBJECTIVE: To examine the HLA-DRB1 phenotypes of patients with Henoch-Schönlein purpura (HSP) and determine if associations exist with disease susceptibility, clinical heterogeneity, or severe systemic complications. METHODS: A retrospective study was performed on an unselected population of patients from Northwest Spain with HSP classified according to proposed criteria. Patients were included in this study if they had at least one year of followup. Fifty Caucasian patients (25 women), 11 of them older than 20 years, were studied. Patients and ethnically matched controls were HLA-DRB1 genotyped from DNA using molecular based methods. RESULTS: During the course of the disease, renal manifestations, especially hematuria, and severe gastrointestinal (GI) manifestations (bowel angina or GI bleeding) were observed in more than 60% of the patients. Twenty percent of patients had persistent renal involvement (renal sequelae). Patients with HSP had a significantly higher frequency of the HLA-DRB1*01 phenotype compared to matched controls. The HLA-DRB1*07 phenotype was also significantly reduced compared with controls. Patients with severe GI manifestations or with persistent renal involvement did not exhibit any specific HLA-DRB1 association other than the underlying association with HLA-DRB1*01. CONCLUSION: HSP in a population from Northwest Spain is significantly associated with HLA-DRB1*01.

Adolescent↗
PubMed2001

Lack of association between intercellular adhesion molecule-1 gene polymorphisms and giant cell arteritis.

OBJECTIVE: Studies have shown an association between HLA-DRB1*04 and giant cell arteritis (GCA). Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms were reported to contribute susceptibility to GCA in Italian patients where susceptibility to GCA is not associated with HLA-DRB1*04 alleles. ICAM-1 is also highly expressed within inflammatory infiltrates of the blood vessels of GCA patients. To investigate the clinical implications of ICAM-1 polymorphisms in GCA, we examined their potential association and influence in the development of visual ischemic complications in a series of patients with GCA from Northwest Spain where GCA susceptibility is associated with HLA-DRB1*04. METHODS: Fifty-eight biopsy proven GCA and 129 ethnically matched controls were studied. Patients and controls were genotyped for ICAM-1 polymorphism at codons 241 and 469 by PCR-RFLP. RESULTS: The distribution of the alleles and genotypes for each ICAM- polymorphism did not show significant differences between GCA patients and controls. Although visual manifestations were significantly more likely to occur in men than women (OR 5.2, p = 0.018), allele and genotype frequencies of ICAM-1 polymorphisms in patients with GCA were not associated with development of visual complications or anemia. Visual complications in GCA were primarily associated with carriage of an HLA-DRB1*04 allele. No evidence was found for interaction between HLA-DRB1*04 and ICAM-1 polymorphism. CONCLUSION: ICAM-1 polymorphisms are not genetic risk factors for the susceptibility and severity of GCA in Northwest Spain.

Aged↗
PubMed2001

HLA-DRB1 associations in biopsy proven erythema nodosum.

OBJECTIVE: To examine the HLA-DRB1 associations of patients with erythema nodosum (EN), establish HLA-DRB1 differences among patients with idiopathic and secondary EN, and identify the HLA-DRB1 associations with specific conditions presenting with EN. METHODS: We conducted a retrospective study of 100 patients (83 women) with biopsy proven EN diagnosed for a defined population in Northwest Spain. Patients were classified into idiopathic or secondary if skin nodules occurred in the context of a well defined disease, or there was a precipitating event in close temporal relationship with the onset of EN. Patients and controls were HLA-DRB1 genotyped from DNA using molecular based methods. RESULTS: At the time of diagnosis no precipitating events or underlying diseases were identified in 35 cases and, due to this, they were considered to be idiopathic. Although strong associations do not appear to exist between HLA-DRB1 and unstratified EN, the idiopathic group showed a significantly lower frequency of HLA-DRB1*04 phenotype compared with controls. Among the patients with secondary EN, the patient subgroup with sarcoidosis exhibited a significantly increased frequency of HLA-DRB1* 13 compared with healthy controls. CONCLUSION: Idiopathic and some groups of secondary EN seem to have different HLA-DRB1 associations. These differences may have prognostic value in identifying patients with specific conditions associated with this syndrome.

Adolescent↗
PubMed2001

Breast cancer audit: adapting national audit frameworks for local review of clinical practice.

OBJECTIVE: To assess the value of using a nationally devised data set for breast cancer audit at a local level for reviewing clinical practice. DESIGN: Audit proforma based on the Scottish Cancer Therapy Network (SCTN) minimum data set and database completed prospectively from January 1999. SETTING: Hairmyres Hospital, a district general hospital within Lanarkshire Acute Services NHS Trust. SUBJECTS: The inclusion criteria were those developed by SCTN for the core minimum data set for breast cancer (SCTN 1999). RESULTS: The results indicate that the SCTN minimum data set can be usefully employed to collect prospective data on breast cancer. The data set is sensitive enough to identify any problem areas, which can be reviewed at greater detail when required. This datset is a robust mechanism for collecting meaningful and comparable data both at a local and national level. CONCLUSIONS: The use of SCTN's minimum data set has been successful for local review of practice. This has led to the identification of "out-liers" from the normal range of process indicators and further internal examination of these at a local level by individual clinicians is under way. This exercise has also proved fruitful in identification of other fields, which can be added to the data set to refine the data collected. The database provided by SCTN is easily manipulated allowing for refinement where required. Breast cancer audit carried out in this way is a useful way of reflecting on clinical practice throughout the multidisciplinary team.

Breast Neoplasms↗
PubMed2000

Subtyping of juvenile idiopathic arthritis using latent class analysis. British Paediatric Rheumatology Group.

OBJECTIVE: To use statistical techniques to identify underlying subtypes of juvenile idiopathic arthritis (JIA) that best explain the observed relationships of clinical and laboratory variables, and to compare the statistically derived subtypes with those defined by the International League of Associations for Rheumatology (ILAR) criteria and examine them for HLA associations. METHODS: Information on 572 patients diagnosed as having JIA was summarized by 10 clinical and laboratory categorical variables (age at onset, large joint involvement, small joint involvement, polyarthritis, symmetric arthritis, spinal pain, fever, psoriasis, antinuclear antibodies [ANA], and rheumatoid factor). Latent class analysis (LCA) was used to identify underlying ("latent") classes that explained the relationships among the observed variables. Statistical models incorporating 5-8 latent classes were applied to the data. RESULTS: The 7-class model was the most appropriate. Patterns of joint involvement and the presence of ANA were influential in determining latent classes. There was some correspondence between the latent classes and the ILAR categories, but they did not coincide completely. Significant differences between the latent classes were seen for 3 HLA haplotypes (DRB1*04-DQA1*03-DQB1*03, DRB1*13-DQA1*01-DQB1*06, and DRB1*08-DQA1*0401-DQB1*0402). CONCLUSION: LCA provides a novel approach to the task of identifying homogeneous subtypes within the umbrella of JIA. In further work, the identified latent classes will be examined for associations with other candidate genes and for differences in outcome.

Adolescent↗