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Biomedical subjects

J Ilonen

Publications and source records attributed to J Ilonen.

At least 145 records · Page 8Linked to original sources

Effect of measles virus infection on MHC class II expression and antigen presentation in human monocytes.

We studied the effect of measles virus (MV) infection on the expression of MHC class II molecules and on the antigen-presenting function in human peripheral blood monocytes in vitro. The expression of HLA-DR, -DQ, and -DP molecules was up to 10-fold higher in MV-infected than that in uninfected monocytes. This effect did not change upon stimulation of monocytes with LPS, and was not mediated by IFN-gamma. In contrast to results obtained with peripheral monocytes, MV infection in a human monocytic cell line, THP-1, did not enhance the basic MHC class II expression, but strongly inhibited the IFN-gamma-induced expression. High levels of MHC class II expression in MV-infected monocytes were associated with capacity to present MV antigens, but the capacity to present unrelated antigens was strongly reduced. These results indicate how MV infection in monocytes may suppress the antigen-mediated T cell proliferation, still allowing the expansion of MV-specific T cell clones.

Antigen-Presenting Cells↗

Clinical characteristics and circulating collagen and laminin metabolites in insulin-dependent diabetic children with joint and skin manifestations.

One hundred seventy-four children and adolescents with insulin-dependent diabetes mellitus were examined for joint contractures and skin manifestations in their hands. Joint contractures were found in 52 (29.8%) and skin manifestations in 29 (16.6%) patients. To eliminate the possible confounding effects of age and duration of diabetes on the variables to be studied, patients younger than 7 y and with a duration of diabetes shorter than 3 y were excluded from the subsequent analyses. Of the remaining 108 children, those with joint contractures had lower serum concentrations of the 7-S domain of type IV collagen and the P1 fragment of laminin than the other patients (p = 0.033) but higher mean glycated Hb levels (p = 0.048). A clear association was noted between the occurrence of joint contractures and skin changes (p = 0.007). Background retinopathy was found in six patients (5.6%), three of whom had stage II joint contractures (p = 0.064). The children with skin changes and those with combined joint and skin manifestations more often had insulin-dependent diabetes mellitus in their first-degree relatives (p = 0.038 and p = 0.043, respectively). No difference in relative height was found between the groups. No association could be seen between disease susceptibility antigens in the HLA-D locus and joint or skin manifestations. The lower levels of circulating collagen and laminin metabolites in the diabetic children with joint contractures suggest that these patients are characterized by a reduced turnover of basement membranes in tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus.

BACKGROUND: Cow's milk has been implicated as a possible trigger of the autoimmune response that destroys pancreatic beta cells in genetically susceptible hosts, thus causing diabetes mellitus. Studies in animals have suggested that bovine serum albumin (BSA) is the milk protein responsible, and an albumin peptide containing 17 amino acids (ABBOS) may be the reactive epitope. Antibodies to this peptide react with p69, a beta-cell surface protein that may represent the target antigen for milk-induced beta-cell--specific immunity. METHODS: We used immunoassays and Western blot analysis to analyze anti-BSA antibodies in the serum of 142 children with insulin-dependent diabetes mellitus, 79 healthy children, and 300 adult blood donors. Anti-ABBOS antibodies were measured in 44 diabetic patients at the time of diagnosis, three to four months later, and one to two years later. RESULTS: All the diabetic patients had elevated serum concentrations of IgG anti-BSA antibodies (but not of antibodies to other milk proteins), the bulk of which were specific for ABBOS: The mean (+/- SE) concentration was 8.5 +/- 0.2 kilofluorescence units (kfU) per microliter, as compared with 1.3 +/- 0.1 kfU per microliter in the healthy children. IgA antibodies were elevated as well, but not IgM antibodies. The antibody concentrations declined after diagnosis, reaching normal levels in most patients within one to two years. The initial decline involved anti-ABBOS--specific antibodies almost exclusively. Much lower serum concentrations of anti-BSA antibodies were found in all 379 control subjects, but only 2.5 percent of them had small amounts of ABBOS-specific IgG. CONCLUSIONS: Patients with insulin-dependent diabetes mellitus have immunity to cow's-milk albumin, with antibodies to an albumin peptide that are capable of reacting with a beta-cell--specific surface protein. Such antibodies could participate in the development of islet dysfunction.

Antibodies↗

Recognition of synthetic peptides with sequences of rubella virus E1 polypeptide by antibodies and T lymphocytes.

Antigenicity of rubella virus E1 polypeptide was analyzed using synthetic peptides with predicted amino acid sequences. Overlapping solid-phase bound peptides were used to define antibody binding domains and a panel of free peptides to study T-cell responsiveness. Several antibody-binding areas including those earlier described to contain major neutralizing epitopes were recognized by human sera positive for rubella antibodies. T-cell lines specific for rubella virus were established from 14 rubella immune subjects. All cell lines responded to rubella virion-derived antigen but only eight (57%) responded to one or more of the synthetic peptides. Individual patterns of peptide recognition were found but peptide 8 representing amino acids 402-422 was most often stimulatory to T-cells lines, either alone (3 subjects) or in combination with peptide 3 (amino acids 245-269) or 3 and 4 (amino acids 269-287). The response was HLA restricted but no single DR specificity for this restriction was identified.

Antibodies, Viral↗

Tumour necrosis factor-beta gene RFLP alleles in Finnish IDDM haplotypes. The Childhood Diabetes in Finland (DiMe) Study Group.

The genes located between class II and class I HLA genes including polymorphic tumour necrosis factor (TNF) genes may contribute to the disease susceptibility in IDDM. Restriction fragment polymorphisms of the TNF-beta gene have been found to be fixed in the major IDDM susceptibility haplotypes, the B62,DR4 haplotype being associated with the 10.5-kb fragment and the B8,DR3 haplotype with a 5.5-kb fragment. We studied this TNF polymorphism in a sample of diabetic families. In all IDDM-associated haplotypes (n = 129) the 5.5-kb allele was more frequent than in haplotypes found only in healthy family members (n = 112) (58.1% versus 40.2%, P < 0.01). Among IDDM haplotypes the B62,DR4 haplotype was characterized by the 10.5-kb TNF fragment, whereas two other common Finnish IDDM-associated DR4 haplotypes--A24,B39,DR4 and A2,B56,DR4--had the 5.5-kb TNF fragment. Both IDDM-associated and non-associated DR3 positive haplotypes were linked to the 5.5-kb fragment. The distribution of various combinations of TNF alleles in IDDM probands (n = 63) did not differ from that expected according to the Hardy-Weinberg distribution. Our results indicate that the 10.5-kb allele of TNF-beta gene as such is not a risk factor contributing to DR4/DQ8-associated susceptibility. Alternatively, there may be heterogeneity in pathogenetic effector mechanisms.

Alleles↗

Differences in HLA antigens between patients with mixed connective tissue disease and systemic lupus erythematosus.

Patients with mixed connective tissue disease (MCTD, n = 32) or systemic lupus erythematosus (SLE, n = 60) were typed for HLA-A, B, C, Dw, and DR antigens. All patients with SLE fulfilled at least four criteria of SLE and the patients with MCTD met the criteria proposed by Alarcon-Segovia (1989). The presence of antibodies to Sm was not considered as an exclusion for MCTD. In the patients with SLE, Dw3, DR3, and the associated B8 and A1 antigens were increased, whereas in the patients with MCTD an increased frequency of Dw4 was found (45 v 18% in controls v 14% in SLE). Of the subtypes of DR4, Dw4 was present in all but one of the DR4 positive patients. The frequency of DR4 in patients with MCTD (52%) differed significantly from that of controls (28%). The strong association of MCTD to one DR4 subtype was further seen in the significantly increased frequency of the B15, DR4 combination. Thus the genetic background seems to be different in patients with MCTD from that in patients with SLE. This could partly explain the clinical differences between these diseases.

Female↗

Nervous system disease, immunological features, and HLA phenotype in Sjögren's syndrome.

Twenty seven patients with primary or possible Sjögren's syndrome with neurological manifestations were compared immunologically with 21 patients with Sjögren's syndrome with an intact nervous system. Patients with Sjögren's syndrome were divided into seropositive and seronegative subgroups with respect to the occurrence of one or more autoantibodies (antinuclear antibodies, rheumatoid factor, antibodies to SS-B) in their serum samples. This study of 48 patients indicates that the spectrum of nervous system disease in seronegative and seropositive subgroups is almost indistinguishable. No significant differences were found in the occurrence of circulating immune complexes, the levels of serum complement C3 and C4, or serum IgA, IgM, and beta 2 microglobulin with respect to the neurological manifestations. The serum IgG level, however, was significantly higher in the patients with Sjögren's syndrome with intact nervous systems than in those with neurological manifestations. No significant association was found between the HLA phenotype and nervous system disease. The occurrence of HLA-B8 and DR3 antigens was, however, significantly higher in those patients with antibodies to SS-B than in those without. This finding supports the suggestion that HLA-B8/DR3 may modulate autoantibody responses rather than disease expression in Sjögren's syndrome.

Adult↗

No association between rheumatoid arthritis and insulin dependent diabetes mellitus: an epidemiologic and immunogenetic study.

To acquire more information on the controversial question of a possible association between rheumatoid arthritis (RA) and insulin dependent diabetes mellitus we searched for insulin dependent diabetes mellitus among patients hospitalized due to RA in 2 rheumatism hospitals in Finland. Nine subjects with insulin dependent diabetes mellitus were found among an annual number of 1460 patients admitted to one of the hospitals due to RA. These figures give a frequency of insulin dependent diabetes mellitus in patients with RA of 0.6% (95% confidence interval 0.2-1.0%), which does not exceed the prevalence of insulin dependent diabetes mellitus among the middle aged population of Finland in general (0.5-0.6%). Accordingly, no overrepresentation of homozygosity for HLA-DR4 was found among the total number of 25 patients with RA as well as insulin dependent diabetes mellitus, though the opposite might be expected as these diseases have a common DR4 association--RA with DR4 and DR1 and insulin dependent diabetes mellitus with DR4 and DR3. Instead, an increased frequency of DR1 (p less than 0.0002) and the antigen combination DR1/4 (p less than 0.01) was found in the subjects with both RA and insulin dependent diabetes mellitus compared with the subjects with insulin dependent diabetes mellitus alone.

Adult↗

B27-bearing HLA haplotypes in rheumatoid arthritis: characterization in Finnish patients.

The frequency of human leukocyte antigen (HLA)-B27 has been found to be increased in rheumatoid arthritis (RA) in Finland and marginally also in some other populations. In the present study HLA-B27-bearing haplotypes in RA patients were found to carry DR1 and DR4 genes more often than do B27 haplotypes in control population. B27;DR4,DW14;DQw7 was a typical B27-DR4 haplotype whereas DR4 in the majority of other haplotypes occurs with Dw4 and DQw8 genes. The result indicates that the B27 association with RA is not independent of DR1 and DR4, but whether the B27;DR4;DQw7 haplotype subjects a person to a higher disease risk than do other DR4 haplotypes, or is associated with a more severe course of the disease, remains to be investigated.

Arthritis, Rheumatoid↗

Low CD4/CD8 T lymphocyte ratio in acute myocardial infarction.

T lymphocyte subsets were analysed using monoclonal antibodies and flow cytometry to determine whether myocardial infarction and cardiopulmonary resuscitation induce changes in these. Groups of 11 infarct patients and 10 patients with past cardiopulmonary resuscitation were compared with 11 age- and sex-matched controls and 12 sepsis patients. The differences in the CD4/CD8 ratios between the four groups were significant (F = 7.71, P = 0.001). The infarct patients had lower CD4/CD8 ratios (mean +/- s.d. 0.83 +/- 0.43) than the control (2.12 +/- 1.13; P = 0.001) or sepsis cases (1.76 +/- 1.05; P = 0.004), but their ratios did not differ from those of the resuscitation group (0.93 +/- 0.79, P = 0.84). The latter group also had lower ratios than the control (P = 0.003) and sepsis groups (P = 0.013). Most infarct patients had an on admission inverted CD4/CD8 ratio which usually returned to normal in the next 2 days. A permanently low CD4/CD8 ratio may be a poor sign prognostically after both myocardial infarction and resuscitation.

Aged↗

Abnormalities within CD4 and CD8 T lymphocytes subsets in type 1 (insulin-dependent) diabetes.

Abnormalities in the proportions of various T lymphocyte subpopulations have been found in a number of autoimmune diseases. Monoclonal antibodies labelled with various fluorochromes were used here to define the percentages of subsets, and especially to divide CD4+ (helper/inducer) and CD8+ (suppressor/cytotoxic) cells into phenotypic subgroups. Blood samples were analysed from 25 patients (age 10.1 +/- 3.7 years) with recently diagnosed insulin-dependent diabetes mellitus (IDDM) and 25 age- and sex-matched control subjects. The percentages of CD4+ cells and CD4+CD45RA+ cells described as naive T helper cells or suppressor/inducers were increased in the IDDM patients (P less than 0.05 and P less than 0.05. Student's t-test, respectively), whereas the percentage of CD4+CD45RA- cells (memory T-helper cells, helper/inducers) was similar in the patients and controls. The percentage of CD8+CD11b+ cells containing suppressor/effector lymphocytes was decreased in the IDDM patients as compared with the controls (P less than 0.01) but no significant difference was seen in total CD8+ cells. The percentages of CD3+ cells and the proportions of these simultaneously positive for HLA-DR antigen (activated T cells) were also increased in the recent IDDM patients (P less than 0.001 and P less than 0.05, respectively), while the proportion of CD20+ B cells was decreased (P less than 0.05). The findings support the view that disturbed immune regulation occurs in IDDM and indicate that further division of T cell subpopulations may clarify our understanding of the disease process.

Adolescent↗

Decreased expression of class II major histocompatibility complex (MHC) molecules on monocytes is found in open-heart surgery related immunosuppression.

The expression of class II major histocompatibility complex (MHC) molecules on monocytes and the relative proportion of immunoregulatory lymphocyte subpopulations were studied from the blood of eight patients undergoing a cardiac operation. The aim of the study was to reveal mechanisms responsible for depression of cellular immunity and B-lymphocyte activation associated with open-heart surgery. A decreased staining of HLA-DR and even more of HLA-DQ class II MHC molecules was found on the monocyte surface in samples taken 2 and 7 days after operation when compared to preoperative values. The relative proportion of monocytes in mononuclear cells increased after surgery, but within lymphocyte subpopulations only a decrease in total T cells and an increased number of activated (HLA-DR positive) T cells were found, whereas the rations between various T cells subsets remained relatively stable.

Adult↗