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Biomedical subjects

R S Pumphrey

Publications and source records attributed to R S Pumphrey.

At least 37 records · Page 2Linked to original sources

Soluble CD23 levels are elevated in the serum of patients with primary Sjögren's syndrome and systemic lupus erythematosus.

The low affinity IgE receptor Fc epsilon RII (CD23) is important in several aspects of T and B cell function. In this study serum levels of soluble CD23 (sCD23) were measured in three groups: 26 female patients with systemic lupus erythematosus (SLE), 21 females with primary Sjögren's syndrome (pSS) and 25 normal healthy females. The concentration of sCD23 was determined using an enhanced chemiluminescent sandwich ELISA developed in this laboratory. Increased levels of sCD23 were observed in pSS and in SLE patients compared with controls (median 23.0 versus 8.6, P less than 0.0002 and 18.1 versus 8.6, P less than 0.002 respectively). While the median level of sCD23 was found to be higher in pSS than in SLE the difference was not statistically significant. Patients with SLE and pSS on glucocorticoid treatment had significantly lower levels of sCD23 than patients not on this treatment (median 28.9 versus 14.4, P less than 0.05). Amongst the control patients sCD23 was inexplicably lower in the female members relative to the males (median 8.5 versus 12.3, P less than 0.05). Although serum IgG and IgA levels were significantly elevated in pSS and SLE patients relative to controls there was no direct correlation between sCD23 and the serum levels of these immunoglobulins. We conclude that B cell hyperactivity which occurs in both pSS and SLE is associated with raised levels of sCD23.

Adult↗

An abnormal T cell repertoire in hypergammaglobulinaemic primary Sjögren's syndrome.

T cell antigen specificity is determined by the products of the genes which encode the variable regions of their receptors. Of the T cell receptor (TCR) variable region gene products examined, only V beta 6.7a TCR-positive lymphocytes were reduced in primary Sjögren's syndrome patients with IgG1 hypergammaglobulinaemia compared with an age-, sex- and HLA-matched control population. The levels of V beta 6.7a T cells were also significantly reduced when these patients were compared with an age- and sex-matched but HLA-unmatched control group and non-tissue typed normal people of both sexes. Since published studies show no such abnormality in rheumatoid arthritis, systemic lupus erythematosus or other autoimmune diseases, this abnormality may reflect a pathogenic process specific to primary Sjögren's syndrome.

Adult↗

Large granular T lymphocytes, neutropenia and polyarthropathy: an underdiagnosed syndrome?

Thirteen patients with expansion of an unusual subset of T lymphocytes, defined by large size, cytoplasmic granularity and CD3+ CD8+ Leu 7+ surface phenotype, are reported. Although morphologically and/or phenotypically abnormal lymphocytes were found in all patients, only five had an absolute peripheral blood lymphocytosis. Ten patients had a bone marrow lymphocytosis. As in previous series, there was a strong association with neutropenia (12 patients) and polyarthropathy (seven patients). The latter group displayed a wide range of articular disease: classical or definite rheumatoid arthritis in four patients and milder non-erosive disease in the remainder. All 13 patients showed evidence of abnormal B cell function: IgM rheumatoid factor was present in nine patients, neutrophil-specific antibodies in six and all showed an increased level of at least one immunoglobulin isotype. These patients may be difficult to distinguish from those with idiopathic neutropenia and Felty's syndrome. Such a distinction may not be made on clinical grounds alone: critical assessment of lymphocyte morphology, bone marrow examination and analysis of lymphocyte phenotype should be considered in all patients with unexplained neutropenia, particularly in the context of arthritis. It is suggested that the true prevalence of this syndrome may have been greatly underestimated.

Aged↗

C-reactive protein levels in serum: a rapid enzyme immunoassay.

A simple and rapid competitive-inhibition enzyme linked immunoassay for serum C-reactive protein (C-RP) is described. The assay has a working range of 4.4-700 mg/l of C-RP, uses two serum dilutions and requires only 90 min to perform. Comparisons are presented between this assay and three commercially-available kits. The assay performs as well as the best of these kits but with added advantages of speed, ease of use and increased working range.

Binding, Competitive↗

Selective polyclonal increase of immunoglobulin G1 subclass: a link with Sjögren's syndrome.

A selective polyclonal increase in IgG1 has been described previously in a group of patients with connective tissue disease; nine of the 16 patients had a prior diagnosis of systemic lupus erythematosus (SLE). A detailed clinical and serological study of 32 patients with this immunoglobulin abnormality has now been made. Most cases showed a characteristic autoantibody profile of antinuclear antibody, rheumatoid factor, and antibodies to Ro and La. Sjögren's syndrome was diagnosed as 'definite' in 16 cases and 'possible' in seven cases by Fox's criteria. The remainder had unclassified connective tissue disease (three), rheumatoid arthritis with dry eyes (two), SLE (one), scleroderma (two), and Raynaud's disease (one). Extraglandular features were invariably present in patients with primary Sjögren's syndrome. The highest concentrations of IgG1 were found in patients with the shortest disease duration. Selective polyclonal increase of IgG1 should alert the doctor to the development of Sjögren's syndrome, usually with extraglandular disease and antibodies to Ro and La.

Acute-Phase Reaction↗

Antiphospholipid antibodies and Mycoplasma pneumoniae infection.

Anticardiolipin antibody levels were measured in 57 patients with Mycoplasma pneumoniae infection and 21 patients with other infections. Significantly more patients in the mycoplasma group had increased IgM and IgG anticardiolipin. Within the mycoplasma group significantly higher titres were found in patients with severe infection (assessed by need for hospital admission) and in patients with cold agglutinins. A tendency for particularly high titres to occur in patients with extra-pulmonary complications was identified.

Adolescent↗

An IgG subclass imbalance in connective tissue disease.

A group of 16 patients with a disproportionate polyclonal increase in their serum IgG1, resulting in raised concentrations of total IgG immunoglobulin, has been discovered. The other IgG subclasses in these patients are either normal or slightly reduced, resulting in an IgG1:IgG2 ratio of at least 10:1. Most cases are marked by the presence of anti-extractable nuclear antigen (anti-ENA) antibodies and high titres of rheumatoid factor and antinuclear antibody. All but one patient has a connective tissue disease, nearly twice the prevalence found in similarly hypergammaglobulinaemic patients without this IgG subclass imbalance. Among patients with systemic lupus erythematosus (SLE), those with the IgG1 disorder have a higher prevalence of high titre rheumatoid factor and antinuclear antibody, but a lower prevalence of anti-double-stranded DNA (anti-dsDNA) antibodies above 30 U/ml. It is suggested that this immunoglobulin abnormality may reflect a unique immunoregulatory dysfunction in these patients.

Adolescent↗

Investigation of IgG4 levels in atopic patients using a competitive inhibition assay employing biotinylated IgG4 myeloma and avidin peroxidase.

Modification of a 'sandwich' ELISA assay developed for the determination of serum IgE levels proved to be unsatisfactory for the measurement of IgG4. This was attributed to the limited capacity of the microtitre plate solid phase which required high serum dilutions in order to measure IgG4 levels. To overcome this problem a competitive inhibition assay was developed with monoclonal anti-IgG4 attached to the plate. In this system biotinylated IgG4 myeloma and sample IgG4 compete for the limited antibody binding sites present on the solid phase. The attached biotinylated myeloma is detected by addition of avidin conjugated with peroxidase and following development with substrate, IgG4 levels are calculated by reference to a calibrated inhibition curve. The inhibition ELISA assay has been used clinically to measure IgG4 levels in atopic and normal individuals and the values obtained correlated closely (r = 0.99) with the IgG4 levels determined by radial immunodiffusion. For 43 atopic dermatitis patients investigated the median IgG4 level was 1.1 g/l which was significantly elevated when compared to a median of 0.385 g/l for 60 blood donors (P less than 0.0001, Mann-Whitney U). Among the 47 hay fever patients investigated the median was 0.6 g/l which, although lower than in atopic dermatitis, was again significantly increased (P less than 0.025). Within this latter group, 25 patients were investigated for the effects of desensitization with commercial grass pollen injections. The total IgG4 showed a variable but significant rise between the start and finish of treatment (P less than 0.01 Wilcoxon signed ranks test).

Binding, Competitive↗

Peritoneal endometriosis in women requesting reversal of sterilization.

Seventy-six women requesting reversal of sterilization underwent at least 1 operative procedure during a 27-month period, and 14 (18.4%) were found to have pelvic endometriosis. The endometriosis patients were noted to have had significantly fewer pregnancies (1.8 versus 2.9, P less than 0.01) before sterilization than those without endometriosis, but the two groups did not differ significantly in mean age (30.8 versus 30.3 years), type of sterilization or in mean number of years since sterilization (5.0 versus 5.5 years). In only two individuals were proximal tubal segment fistulas found at the time of reversal, and neither had endometriosis. We conclude that pelvic endometriosis is more common in patients with bilateral tubal occlusion than previously suspected and that its presence indicates that endometriosis implants can persist for prolonged periods of time, can give rise to new implants, or do not require the tubal reflux of menstrual debris to form.

Adult↗

Cyclical eosinophilia: a manifestation of periodic haemopoiesis?

A patient is described who has had a marked eosinophilia of unknown cause for 9 years in association with episodic facial swelling. Weekly blood counts for 8 months showed cyclical variations in eosinophils, neutrophils and monocytes (mean cycle length 35 d). Marrow culture studies showed fluctuation in the incidence of granulocyte-macrophage colonies (GM-CFC), and the proportion of eosinophil colonies was higher than the values reported for normals. The blood lymphocyte T4/T8 ratio was reversed, due to an increase of T8+ cells. It is suggested that this condition is a rare form of periodic haemopoiesis.

Aged↗

Evidence for circulating complexes containing IgE in patients with atopic dermatitis.

18 out of 34 patients with atopic dermatitis were shown to have 5-32% of their serum IgE present in a high molecular weight (HMW) form (470,000 daltons). There was no simple correlation between the amount of HMW and the total serum IgE. The HMW peak was not affected by freezing and thawing the serum, but the complexes could be split by lowering the pH of serum fractionation. Some patients were tested sequentially on different occasions and although their clinical status may have altered during this time, there was no marked alteration of the HMW fraction. Results are compared with patients with raised IgE due to parasitic infections. Anti-IgE antibodies have been demonstrated in the HMW fraction.

Adult↗

Failure of delayed hypersensitivity skin testing to predict postoperative sepsis and mortality.

Delayed hypersensitivity skin reactions to a battery of recall antigens, haemoglobin and albumin concentrations, arm-muscle circumference, and percentage of ideal weight were determined before operation in 244 patients undergoing elective major surgery. Depressed skin reactions were found in 70 patients (28%), but this group did not have significantly higher sepsis or mortality rates when compared with patients with normal reactions. Significant associations were found between depressed skin reactions and increasing age, anaemia, hypoalbuminaemia, low arm-muscle circumference, and low weight. Patients with benign and malignant disease had similar distributions of skin reactions. Hypoalbuminaemia was associated with a higher rate of serious postoperative sepsis, and hypoalbuminaemia, low arm-muscle circumference, and low weight were all associated with a higher mortality. These results suggest that the routine use of delayed hypersensitivity skin testing in the preoperative assessment of surgical patients is not justified.

Abdomen↗