Biomedical subjects
W Thomson
Publications and source records attributed to W Thomson.
Haplotypes bearing HLA-A, -B, and -DR: Bf and C4 genes in rheumatoid arthritis families.
We have compared haplotypes bearing HLA-A, -B, -DR; Bf and C4 genes in 54 rheumatoid arthritis (RA) and 24 control families. There was no statistically significant differences in C4A or C4B gene frequencies between RA and control groups, although there were trends for C4B*Q0 to be reduced and C4B2 to be increased in DR4 positive RA compared with DR4 positive controls. The lack of any strong association between C4 variants and RA overall makes it unlikely that the association between RA and genes within the MHS represents a direct effect of variants within the C4A or C4B loci themselves. On comparison of DR4-bearing haplotypes, the haplotype B15-BfS-DR4 was increased fourfold and the B44-Bfs-DR4 haplotype was less frequent in the RA group. When C4 variants were also considered, the haplotype B44-C4B*Q0-C4A3-BfS-DR4 was nine times less frequent in RA patients than in controls. The observation that different DR4 bearing haplotypes may confer either increased or decreased susceptibility to RA suggests either that it is unlikely that DR4 itself is involved in the disease process or that specific haplotypic combinations are important. Thirty-two RA patients were HLA-DR4 negative. No single DR4 negative haplotype was found to confer significantly increased susceptibility to RA.
The contribution of direct immunofluorescence to the diagnosis of lupus erythematosus.
The contributions of direct immunofluorescence, light microscopy and serology to the investigation of 52 patients with possible lupus erythematosus were studied. Direct immunofluorescence was found to be most valuable in the investigation of possible systemic lupus erythematosus whilst only of supportive value in the investigation of possible chronic discoid lupus erythematosus. The importance of performing light microscopy before direct immunofluorescence in cases of possible chronic discoid lupus erythematosus is shown.
Complement C4B-null alleles in Felty's syndrome.
C4A and C4B allotypes were compared in 20 patients with Felty's syndrome (FS), 52 patients with rheumatoid arthritis (RA), and 55 control subjects. Nineteen of the FS patients had HLA-DR4. A C4B-null allele was more frequent in the patients with FS (60%) than in either the RA patients (15%) or the control subjects (26%). Only the differences between patients with FS and those with RA remained statistically significant when DR4 positive subjects were compared. The C4B null allele may identify individuals within the rheumatoid population who are at risk of developing particular systemic complications.
Control of iron absorption in hemochromatosis. Mucosal iron kinetics in vivo.
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Chromosome 14 markers in rheumatoid arthritis.
Phenotype frequencies for variants of the chromosome 14 markers, alpha 1 antitrypsin (protease inhibitor--Pi), and immunoglobulin heavy chain gene allotypes (Gm and Am) were examined in affected and unaffected members of multicase rheumatoid arthritis (RA) families and compared with published population data. Significantly higher frequencies of phenotypes containing Pi*Z and Pi*S were observed in unrelated index RA cases compared with UK population data. There was also a higher frequency of Pi*Z in family members without RA than in population controls but no such difference for the frequency of Pi*S. No difference in the frequency of PiM1M2 heterozygotes was seen between patients with RA and population controls. An examination of clinical data failed to show any relation between any particular feature of RA and positivity for Pi*Z or Pi*S. No significant differences in frequency of Gm phenotypes were observed between patients with RA and controls. Significant association was found, however, between Pi*Z and Gm phenotypes containing Gm(zax;g). These associations are interpreted as indicating linkage disequilibria between these alleles. No interactions between DR4 and either G1m(z), (a), or (x) allotypes were apparent in patients with RA. A significant association was seen in the index RA cases between DR4 and Pi phenotypes carrying Z or S alleles. Observations from this study provide evidence for the existence of a genetic component for RA susceptibility encoded on chromosome 14. An interactive effect of these genes with DR4 towards susceptibility appears likely.
Calcific valvular aortic stenosis with and without mitral anular calcium.
Seventy-six consecutive patients, mean age 66 +/- 9 years (+/- standard deviation), with isolated aortic valve replacement for calcific valvular aortic stenosis (AS) were studied. Mitral anular calcium (MAC) was detected by echocardiography in 45 patients (59%). Patients with MAC were older (p less than 0.01), had greater peak systolic aortic valve gradients (p less than 0.025), lower cardiac indexes (p less than 0.025) and smaller valve areas (p less than 0.05) than patients without MAC. Thirty-three percent of patients (15 of 45) with MAC required permanent pacemaker implantation after aortic valve replacement, compared with only 10% of patients (3 of 31) without MAC (p less than 0.025). During the follow-up of 7 years (mean 3.8 +/- 1.6), 27% of patients (12 of 45) with MAC died from cardiac causes, compared to only 7% (2 of 31) without MAC (p less than 0.025). Thus, patients with AS and MAC are older, have more severe AS, more frequently undergo permanent pacemaker implantation after aortic valve replacement and more frequently die of cardiac causes than patients with AS and no MAC during follow-up.
Echocardiographic and electrocardiographic characteristics of patients with hypertrophic cardiomyopathy with and without mitral anular calcium.
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Deaths from meningococcal infection in Lanarkshire 1984-1986.
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A comparison of clinical and immunogenetic features in familial and sporadic rheumatoid arthritis.
Clinical and immunogenetic factors were compared in 214 patients with sporadic rheumatoid arthritis (RA) and 117 patients from 52 multiplex families. Sex distribution, articular disease severity and seropositivity for rheumatoid and antinuclear factors were similar in familial and sporadic disease. There was a trend for Sjögren's and Felty's syndromes to be more frequent in familial RA but extraarticular disease features were otherwise similar in the 2 RA disease groups. Mean age of onset was 41.1 years in familial and 46.5 years in sporadic RA (p less than 0.0006); 67% of family probands, 74% of affected relatives and 57% of sporadic patients were HLA-DR4 positive (p less than 0.05 affected relatives vs sporadic). The similarity of clinical features found in familial and sporadic RA justifies the use of families with RA to study aspects of disease pathogenesis.
Genetic variants of complement component 3 (C3) in DR4 positive and DR4 negative rheumatoid arthritis.
C3 allotypes were defined in 86 Caucasoid patients with rheumatoid arthritis living in the north west of England and in 80 local, healthy controls. C3 allotype and phenotype frequencies were similar in RA (whether DR4 positive or negative) and control groups.
alpha 1 Antitrypsin (PI) allotypes in rheumatoid arthritis.
alpha 1 Antitrypsin (PI) phenotypes were defined in 144 patients with rheumatoid arthritis (RA) and in 223 normal controls. The frequencies of the rare F, S, and Z variants were similar in RA and control groups. No relationships were found between PI allotypes and rheumatoid disease severity or autoantibody titre. The PI M1M2 phenotype was increased in frequency in the RA group, and phenotype frequencies in DR4 positive and negative disease were similar. These results support the suggestion that genes on the 14th chromosome which are linked to PI predispose to RA.
C3, Gm, and Pi polymorphisms in rheumatoid arthritis.
This paper reviews the associations between RA and three non-MHS genetic markers: C3, Gm, and Pi. There is no evidence to suggest that genes linked to C3 predispose to RA. However, there is evidence to suggest that genes on chromosome 14, linked to both Gm and Pi, do influence susceptibility to RA and further studies of this chromosome are indicated.
Are major histocompatibility system class III products independent markers for susceptibility to rheumatoid arthritis?
Three components of the complement pathway C2, Factor B, and C4 are coded for by four genes C2, Bf, C4A, and C4B in the class III region of the major histocompatibility system in man. Studies of the polymorphism of these plasma proteins have shown associations of BfS, C2C, and C4B3 (2.9) with RA. Family studies have shown that these markers occur together, usually on DR4 positive haplotypes and in particular on the A2-Cw3-Bw62-C4B3-C4A3-BfS-C2C-DR4 haplotype. It is argued that Class III gene products are unlikely to be independent markers of susceptibility to RA.
Rheumatoid arthritis: inheritance and association with other autoimmune diseases.
This paper reviews the significance of the associations between rheumatoid arthritis (RA) and both diabetes mellitus and autoimmune thyroid disorders (ATD). All three disorders are thought to result from an interaction between genetic susceptibility and environmental factors. There is a probable real but not dramatic aggregation of insulin-dependent diabetes mellitus (IDDM) in the families of RA probands and a significant aggregation of ATD in both first- and second-degree relatives of RA probands. HLA-linked genes predispose to all three disorders while genes linked to Gm have been implicated in predisposition to RA and ATD. Within the HLA region two or more genes may predispose independently to RA; one of these genes is in linkage disequilibrium with HLA-DR4 and a second is in linkage disequilibrium with DR1 and 3. The familial aggregation of RA and IDDM is at least partially attributable to a single gene linked to HLA-DR4 predisposing to both disorders. By contrast, although 'DR4 negative RA' seems more frequent in sibships containing members with ATD, the familial aggregation of RA and ATD cannot be accounted for by a single gene linked to HLA predisposing to both disorders. Neither can this familial aggregation be accounted for by a single gene linked to Gm predisposing to RA and ATD so that any genetic predisposition common to both disorders is likely to involve at least a third locus which is still to be defined. A simple model with an interaction between at least three independent genetic loci and genetic heterogeneity is proposed to account for the known facts concerning the genetic susceptibility to RA.
Rubella: immunity and vaccination in schoolgirls.
Of 191 schoolgirls, 128 volunteered to take part in a feasibility study of serotesting before and after rubella vaccination, and all responded to RA 27/3 vaccine. Had the serum samples been taken by a fingerprick method the number of volunteers would probably have increased considerably. A change in policy for rubella vaccination to testing both before and after vaccination would cost no more than the existing policy, would ensure primary response, and would differentiate those women who were protected by the vaccine from those with antibody to wild virus.
Clinical characteristics of patients younger than 60 years with mitral anular calcium: comparison with age- and sex-matched control subjects.
The clinical characteristics of 107 patients younger than 60 years with mitral anular calcium (MAC) were compared with those of 107 age- and sex-matched control subjects. The patients with MAC included 55 men and 52 women, mean age 51 years. The control group included 55 men and 52 women, mean age 51 years. Patients with MAC had a higher prevalence of cardiomegaly on chest x-ray (p less than 0.0001), left atrial and left ventricular enlargement by echocardiography (p less than 0.0001), precordial murmurs (p less than 0.0001), diabetes mellitus (p less than 0.0001), systemic hypertension (p less than 0.025) and total conduction defects on surface electrocardiograms (p less than 0.0001) compared with the age- and sex-matched control subjects. The mean serum phosphorus and product of serum calcium and phosphorus were higher in patients with MAC (p less than 0.0025) than in the control subjects. The prevalence of coronary heart disease, aortic stenosis and hypertrophic cardiomyopathy and the mean serum cholesterol, triglyceride, total protein, albumin, creatinine, alkaline phosphatase and calcium levels were not significantly different between patients with MAC and the control subjects.
Prognostic significance of exercise-induced complex ventricular arrhythmias in coronary artery disease with normal and abnormal left ventricular ejection fraction.
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