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Biomedical subjects

K Gelsthorpe

Publications and source records attributed to K Gelsthorpe.

At least 37 records · Page 2Linked to original sources

Factors governing the human immune response to injected insulin.

Seventy-nine patients were observed prospectively during their initial period of treatment with conventional bovine insulins. Insulin antibody levels 6 months after starting insulin therapy did not correlate with age, gender or beta cell function at onset of treatment. Patients who required soluble insulin in addition to isophane insulin developed higher levels of insulin antibody. Patients bearing the HLA-B8, DR3 and C4AQO alleles had lower levels of insulin antibody, whereas those bearing DR7 produced significantly higher levels. Other alleles at the C4A, C4B, C2, factor B or Gm loci did not appear to have a significant effect on insulin antibody production. The hyporesponsiveness of B8/DR3/ C4AQO -positive individuals probably reflects a non-specific abnormality of immunity whereas the enhanced responsiveness of those positive for DR7 suggests the presence of a specific immune response gene for insulin.

Adolescent↗

Histocompatibility antigen frequencies in patients with chronic lymphocytic leukaemia: possible identification of a subgroup with relatively benign disease.

A series of 57 patients with chronic lymphocytic leukaemia was typed for HLA-A, B and DR antigens and compared with a control population of equal size. There was an increased frequency of HLA-A1 and B8 in the patient group, although it was not statistically significant after allowance for the number of specificities tested. A subgroup of patients lacking both A1 and B8 differed from the others in sex ratio, degree of lymphocytosis and incidence of hypogammaglobulinaemia at presentation. This subgroup also had less need for treatment within 6 months of presentation. While these findings must be considered preliminary, it is possible that tissue typing may help to identify patients with a relatively benign form of the disease.

Aged↗

HLA phenotype and insulin antibody production.

HLA phenotypes have been determined in 79 patients as part of a prospective study of factors governing the immune response to injected insulin. IgG insulin antibody levels 6 months after starting treatment with bovine insulin were significantly higher in patients bearing HLA-DR7 and this in conjunction with the lack of a similar pattern in the IgG response to Helix pomatia haemocyanin, suggests the presence of an immune response gene for insulin. The hyporesponsiveness of HLA-B8/DR3/C4AQ0 positive individuals is more likely to reflect a non-specific abnormality of immunity.

Adolescent↗

Antibody-dependent and phytohaemagglutinin-induced lymphocyte cytotoxicity in systemic lupus erythematosus.

An investigation of cell-mediated cytotoxicity in 22 patients with systemic lupus erythematosus (SLE), using both whole blood and purified peripheral blood mononuclear cells (PBM) to measure antibody-dependent (ADCC) and phytohaemagglutinin (PHA)-induced lymphocyte cytotoxicity for Chang liver cells, has revealed 2 distinct abnormalities in patients with active disease. PHA-induced cytotoxicity was found to be selectively reduced in whole blood assays only (P less than 0.05), whereas ADCC was impaired in both whole blood (P = 0.02) and PBM (P less than 0.05) assays, when comparison was made with 52 normal controls. The addition of patients' sera to corresponding assays utilizing control PBM confirmed that the impaired PHA-induced cytotoxicity resulted from circulating inhibitory serum factors. Surprisingly little effect, however, was exerted on ADCC assays. These findings suggest that there is a reduction in numbers and/or functional capacity of Fc-receptor cells in active SLE, which may have pathogenetic implications.

Adult↗

Location of the gene for 21-hydroxylase deficiency.

HLA typing of 33 families with one or more children suffering from congenital adrenal hyperplasia confirmed that the gene for 21-hydroxylase deficiency is closely associated with the HLA region. Analysis of two families in which recombination of chromosome 6 had occurred indicated that the gene locus is between the A and D loci of the HLA region. The rare allele Bw47 was observed in 18 parents and was always associated with the carrier state for 21-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital↗

Clinical and immunological associations in myasthenia gravis. 1: Autoantibodies.

Associations between female sex, HLA B8, positive anti-thyroid microsomal antibody and, to a lesser extent, antinuclear antibody were seen in 34 patients with myasthenia gravis. This supports the concept that the disease is heterogeneous. Anti-DNA antibodies, which were present in 62% of the patients, did not show such associations.

Adult↗

The association of HLA-B8 with visceral disease in systemic sclerosis.

Seventy-one patients with systemic sclerosis (SS) were typed for twenty-seven HLA alleles of the A and B loci, and the findings were related to both the extent of visceral disease and tests of cellular immune competence in a subgroup of fifty-two of these patients. Nineteen pa;ients with widespread visceral involvement and more rapidly progressive disease had an increased frequency of HLA-B8 (relative risk = 4.14; P less than 0.05) when compared to thirty-three less severely affected patients and 3000 controls. Patients with severe and progressive disease also had defective cell-mediated immunity with reductions in both the numbers of circulating thymus-dependent (T) lymphocytes and in the lymphocyte transformation response to phytohaemagglutinin. These findings suggest that a genetic factor, such as an abnormal immune response gene, may be involved in the progression of the disease.

Adult↗

A relation between HLA antigens and clinical features in patients with acquired valvular heart disease.

Analysis of the HLA antigen patterns in patients with acquired valvular heart disease showed that antigens A29 and AW30/31 occurred more often in those patients whose valvular disease was not preceeded by a history of rheumatic fever or chorea. Patients with no rheumatic history but with antigen A29 or AW30/31 had clinical features that distinguished them from others with valvular disease--namely, (a) isolated mitral valve disease and (b) the need for surgery, often at an early age, after a relatively short duration of symptoms.

Adult↗

Some parameters of lymphocyte antibody activity through pregnancy and further eluates of placental material.

One hundred and sixty-nine pregnancies with lymphocyte cytotoxic antibody activity were found out of 851 full term pregnancies. A rise in incidence of antibody activity was found through first, second and third pregnancies. The average scores for antibody titre and avidity were similar for antibodies to the A and B loci in first, second and third pregnancies though individual scores varied greatly. Five cases are reported where antibody activity was not detectable till the 6-month post-natal stage. ABO compatibility did not have any effect on antibody production. A further 40 placental eluates are reported with the same findings as reported previously.

ABO Blood-Group System↗

Serological identification of Ia antigens: report of a British region Ia workshop.

In preparation for the 7th International Histocompatibility Workshop 13 laboratories in the British Region participated in a local workshop. One hundred and twenty-three sera which had been previously shown to have activity on either normal B cells, CLL cells or B cell lymphoid lines in the absence of HLA-A, B or C activity were exchanged between the laboratories. These sera were tested on a total of 212 B cells, 101 CLL cells, 76 T cells and 76 lymphoid cell lines. The data was collected and analyzed in Oxford. The analysis showed that six groups of sera could be distinguished. When these groups were compared with the D locus typing of some of the lymphoid lines which were derived from individuals used as MLC typing cells, they were seen to have significant associations with D locus antigens. The serological groups defined were therefore given numbers corresponding to the D locus numbers they associate with, i.e. UK1 is associated with DW1 and so on for UK2, 3, 4, 5 and 7. Comparison of typing techniques showed that long incubation both with antiserum and then with complement, 1 hour + 2 hours gave the best and most reproducible reactions on normal B cells. Residual anti-HLA-A, B or C activity in some of the sera even after platelet absorption showed the importance of adequate checking on T cells after absorption.

Antibody Specificity↗

HLA antigens and acquired valvular heart disease.

The frequency of HLA antigens was determined in 133 patients with acquired valvular heart disease and compared with the frequency of HLA antigens in 1,000 normal individuals by the relative incidence ratio method of Woolf (1955). No significant increases were observed. However, when the patients were divided into those with no rheumatic history and those who have had rheumatic fever or chorea, a significant increase in AW 30/31 and A29 was observed in the group with no rheumatic history.

Chorea↗