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M Honeyman

Publications and source records attributed to M Honeyman.

At least 19 recordsLinked to original sources
PubMed2000

Islet autoimmunity in infants with a Type I diabetic relative is common but is frequently restricted to one autoantibody.

AIMS/HYPOTHESIS: To determine the sequence of development of islet autoantibodies and their relation to HLA genes in infants at risk for Type I diabetes followed from birth. METHODS: We followed 357 (189 male, 168 female) infants, with a first degree relative with Type I diabetes for a mean of 3 years from birth. Human leukocyte antigen typing and assays for insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADAb) and tyrosine phosphatase IA2 (IA2Ab) antibodies were done on cord blood, and venous blood was sampled every 6 months for IAA, GADAb and IA2Ab. RESULTS: We did not find any antibodies in 263 (73%) infants; 50 (14%) were positive for a single antibody once, 19 (5%) for a single antibody more than once and 25 (7%) for two or more antibodies. Of the latter, 10 (2.8% overall) were persistently positive; they had higher frequencies of HLA DR4 (p < 0.01) and HLA DR3, 4 (p < 0.05). Of the group persistently positive for two or more antibodies four infants developed diabetes. Insulin autoantibodies were the first ones to develop in 64% of infants with two or more antibodies. CONCLUSION/INTERPRETATION: Infants with high risk HLA-DR alleles and multiple antibodies at high risk for diabetes were identified. A much larger group of infants had transient low level increases usually of a single antibody. Whereas transient low level positivity could be attributed to difficulties with assay technique and cut off levels for normality, the results overall support the phenomenon of transient 'self limited' islet autoimmunity in at risk infants.

Aging↗
PubMed2000

Toxic shock syndrome associated with newly diagnosed type I diabetes.

Studies of two post-mortem pancreata of children at the onset of type I diabetes have suggested activation and expansion of islet infiltrating T cells by a superantigen. We present the first reported case of a superantigen mediated disease, toxic shock syndrome (TSS), occurring at the diagnosis of type I diabetes. A 12-year-old girl presented with TSS and newly diagnosed diabetes with ketoacidosis. At presentation she was unconscious, febrile and hypotensive, with a desquamating erythematous rash and Kussmaul breathing. During resuscitation, her renal impairment, diarrhoea, thrombocytopaenia and ketoacidosis resolved. Vaginal discharge and blood cultures grew Staphylococcus aureus. T cell studies at 2 weeks after diagnosis detected a high level of spontaneous and islet antigen-specific proliferation with associated interleukin-10 production compared to human leucocyte antigen DR matched controls.

Anti-Bacterial Agents↗
PubMed1994

Assessment of CD4 expression by early T precursor cells and by dendritic cells in the human thymus.

The adult mouse thymus contains a minute population of early lymphoid precursor cells that express moderate levels of CD4. We searched for a corresponding population of early T precursors in the infant human thymus, by first depleting the majority of more mature thymocytes, then using immunofluorescence and flow cytometry to analyze cells bearing a range of early T lineage markers. No discrete population of early T precursors expressing CD4 was observed, in contrast to the murine thymus. Most putative very early human thymocytes were CD4-8-3-1-2lo44+34+7hi class I MHChi class II MHC-. However, a distinct population of human thymic dendritic cells expressing high levels of CD4 was isolated. These were CD4hi8-3-1-2-44+34-7- class I MHChi class II MHChi, and lacked markers of B cells, NK cells, or myeloid cells. They were large cells that exhibited dendritic morphology after brief periods of culture, and they were efficient stimulators of allogeneic T cells. The biologic implications of CD4 expression by thymic dendritic cells are discussed.

Adolescent↗
PubMed1992

Failure of Epstein-Barr virus-specific cytotoxic T lymphocytes to lyse B cells transformed with the B95-8 strain is mapped to an epitope that associates with the HLA-B8 antigen.

There are two types, A and B, of Epstein-Barr virus (EBV) and B95-8 represents the common type A laboratory strain. Herein, we show in a family study that paternal EBV-specific cytotoxic T lymphocytes (CTL) generated in short-term cultures following stimulation with the autologous B95-8-transformed lymphoblastoid cell line (LCL) or B cells freshly infected with the B95-8 isolate did not lyse haploidentical B95-8 LCL expressing the HLA-A1, -B8, -DR3 paternal haplotype. In contrast, the haploidentical B95-8 LCL expressing the HLA-A11, -B51, -DR7 paternal haplotype was strongly lysed. Moreover, paternal CTL generated in response to stimulation with the B95-8 LCL expressing the haploidentical HLA-A1, -B8, -DR3 paternal haplotype included an allogeneic response against the maternal haplotype but no EBV-specific response as shown by the poor lysis of the autologous LCL target cells. However, stimulation with the haploidentical HLA-A11, -B51, -DR7 paternal haplotype resulted in the generation of both an allogeneic and an EBV-specific response. CTL clones were generated from two HLA-B8+ donors in response to stimulation with the autologous type A LCL transformed with wildtype EBV. The clones were cross-reactive for an immunodominant B95-8-associated peptide epitope that interacted with the HLA-B8 allele but failed to lyse B95-8-transformed LCL targets unless the targets were pre-coated with the exogenous peptide. A CTL clone that was initially stimulated with the autologous BL74 LCL lysed the spontaneous autologous LCL and spontaneous LCL from an HLA-B8+ donor, but failed to lyse the B95-8 LCL from that donor. The observed haplotype preference can be explained in terms of sequence variation between the B95-8 and the corresponding wildtype epitope. Our findings may help to clarify the role of EBV in the pathogenesis of primary Sjögren's syndrome which is closely associated with HLA-B8.

Cell Transformation, Viral↗
PubMed1992

Searches for matched and closely matched related and unrelated bone marrow donors undertaken in a single paediatric unit.

Information regarding the likelihood of finding suitable marrow donors is limited. In order to determine this potential, all patients who received their primary care at a single paediatric institution over a 9 year period and in whom tissue typing studies were initiated are reviewed. Forty-five (31.3%) of 144 patients had a sibling who was human leucocyte antigen (HLA) identical. A further 16 (11.2%) patients had immediate or more distant relatives who were either HLA identical (2.7%) or matched for five of six HLA antigens (8.3%). The possibility that a parent was closely matched with the patient was suggestive from the typing of siblings alone in only half the cases. Unrelated HLA matched donors were identified in four (27%) of 17 bone marrow bank searches. Overall, a potential related donor was identified within the family for 42% of patients and this figure rose to 45% when successful marrow bank searches were included. It can be concluded that initial typing should include both the parents and siblings. If a suitable donor is not found then an extended family and/or bone marrow bank search will identify additional suitable donors in a significant number of families.

Bone Marrow Transplantation↗
PubMed1991

Bone marrow transplantation in children using closely matched related and unrelated donors.

Seventeen bone marrow transplants were undertaken on 15 patients with leukemia or aplastic anemia using marrow from closely matched (phenotypic or five out of six HLA-A, B and DR antigen matched related and unrelated) donors. Donors were siblings (four), parents (seven), aunt (one), great aunt (one) or matched unrelated (two). When compared with transplants using matched sibling donors, survival was not different (51.4 +/- 13.4% vs. 48.1 +/- 9.6%; p = 0.87) but transplant-related complications and morbidity were higher as follows: graft-versus-host disease (GVHD) (87% vs. 15%; p less than 0.001), interstitial pneumonitis (59% vs. 14%; p less than 0.003), days in hospital (51 vs. 26; p less than 0.001), and chronic transplant related morbidity 50% vs. 11%; p + 0.033). The age of donors who were closely matched was significantly greater than that of their recipients (29.7 +/- 13.9 years vs. 8.1 +/- 3.1 years; p less than 0.001) and was associated with poorer transplant outcome. Median transplant-related complication-free survival for patients receiving transplants from age non-disparate donors was 53 months (range 18-86 months) compared with 12 months (range 2-42 months) for age disparate donors (p = 0.028). Transplants from closely matched donors were undertaken in the ratio of one to every three matched donors, indicating the importance of this source of marrow in a transplant program.

Adult↗
PubMed1989

Analysis of human T cell response to two Plasmodium falciparum merozoite surface antigens.

Eight novel human T cell epitopes were identified within the two major merozoite surface antigens (MSA1 and MSA2) of Plasmodium falciparum using synthetic peptides. All except one of the peptides conformed structurally to an amphipathic alpha helix and three out of the four MSA1 peptides also contained sequences containing the Rothbard motif. Peptide MSA2/2, which fitted none of these criteria, was recognized by our donors to a similar degree as the other peptides. This peptide also contains a B cell epitope. Proliferative responses were obtained in both immune and nonimmune donors, however, the number of responses in the immune donor group was significantly higher. There was no correlation between the level of proliferation and antibody titers to these antigens. No peptides were preferentially recognized in association with specific HLA class II antigens.

Animals↗
PubMed1988

Homozygous osteogenesis imperfecta unlinked to collagen I genes.

In a consanguineous pedigree in which a severe type of osteogenesis imperfecta was segregating as an autosomal recessive trait, analysis of genetic markers for both collagen I structural loci COL1A1 and COL1A2 showed that the phenotype was unlinked to either locus.

Collagen↗
PubMed1985

Prenatal x-ray exposure and childhood cancer in twins.

We conducted a case-control study to investigate the relation between prenatal exposure to x-rays and childhood cancer, including leukemia, in over 32,000 twins born in Connecticut from 1930 to 1969. Twins as opposed to single births were chosen for study to reduce the likelihood of medical selection bias, since twins were often exposed to x-rays to diagnose the twin pregnancy or to determine fetal positioning before delivery and not because of medical conditions that may conceivably pre-dispose to cancer. Each of 31 incident cases of cancer, identified by linking the Connecticut twin and tumor registries, was matched with four twin controls according to sex, year of birth, and race. Records of hospitals, radiologists, and private physicians were searched for histories of x-ray exposure and other potentially important risk factors. Documented prenatal x-ray exposures were found for 39 per cent of the cases (12 of 31) and for 26 per cent of the controls (28 of 109). No other pregnancy, delivery, or maternal conditions were associated with cancer risk except low birth weight: 38 per cent of the cases as compared with 25 per cent of the controls weighed under 2.27 kg at birth. When birth weight was adjusted for, twins in whom leukemia or other childhood cancer developed were twice as likely to have been exposed to x-rays in utero as twins who were free of disease (relative risk, 2.4; 95 per cent confidence interval, 1.0 to 5.9). The results, though based on small numbers, provide further evidence that low-dose prenatal irradiation may increase the risk of childhood cancer.

Adolescent↗