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J Ilonen

Publications and source records attributed to J Ilonen.

At least 163 records · Page 9Linked to original sources
PubMed1991

HLA-DQB1 alleles and absence of Asp 57 as susceptibility factors of IDDM in Finland.

It has been proposed that negatively charged aspartic acid at position 57 of the HLA-DQ beta-chain determines resistance to development of insulin-dependent diabetes mellitus (IDDM), whereas genetic susceptibility to IDDM correlates with a neutral amino acid residue. The disease rate is very low in Oriental populations with high frequencies of Asp 57. This raises a question whether the high incidence of IDDM in Finland could be explained by the distribution of this disease marker. In this study, the polymerase chain reaction products of 86 diabetic patients and 115 nondiabetic control subjects were analyzed with seven sequence-specific oligonucleotide probes. Only 25.5% of the diabetic subjects were phenotyped as Asp 57+ compared to 82% of control subjects, which suggests that Asp 57 negativity is a definite risk marker for developing IDDM in Finnish patients. However, the susceptibility conferred by various non-Asp and Asp haplotypes was not equally strong: DQw8 was the most important risk marker and DQw6 the most protective one. The frequency of Asp 57+ DQw4 was similar in diabetic patients and control subjects. The highest genotype-associated relative risk was defined by DQw2/DQw8 heterozygosity (RR 91), whereas it was 13 for non-Asp homozygosity. In the control subjects, the frequency of Asp 57+ phenotypes was higher than in several white populations with lower IDDM incidence figures. We conclude that the disease risk in Finland appears to be most strongly related to specific Asp 57- alleles, although other HLA- or non-HLA-associated genes may also contribute to IDDM susceptibility in this population.

Adolescent↗
PubMed1990

HLA-DQ beta-chain restriction fragment length polymorphism as a risk marker in type 1 (insulin-dependent) diabetes mellitus: a Finnish family study.

Finnish Type 1 (insulin-dependent) diabetic families were analysed for HLA-DQ beta-chain polymorphism using a short intron-specific probe. A simple hybridization pattern was obtained in which all fragments were associated significantly with Type 1 diabetes. The simultaneous presence of two different risk markers, the allelic 12-kilobase and 4-kilobase fragments were strongly associated with Type 1 diabetes since 50% of the patients had this combination compared with only 2% of the control subjects. The cosegregated 7.5/3.0 kilobase fragments, which were associated with HLA-DR2 and DRw6 were not detected among the diabetic patients but were present in 48% of the control subjects. Our results provide further support for the location of susceptibility determining factors in the HLA-DQ gene area. The clear-cut, simple restriction fragment length polymorphism pattern obtained here, which bears a resemblance to a two allelic system, therefore makes this method applicable for estimating the risk of Type 1 diabetes at the population level.

Adolescent↗
PubMed1990

Cloning of human T cells specific for measles virus haemagglutinin and nucleocapsid.

T cell lines specific for measles virus (MV) were generated from blood of two DR1/DR2 heterozygous healthy donors with a history of past measles infection. The antigenic specificity of 66 T cell clones derived from the lines was studied in a blastogenic assay using whole measles virus and two purified virus components, haemagglutinin and nucleocapsid. Thirty-nine of the clones were specific for one of the two purified antigens. None of the seven synthetic peptides covering 20% of the MV haemagglutinin amino acid sequence stimulated T cell clones with haemagglutinin specificity. Responsiveness of the majority of the clones were restricted by HLA-D/DR antigens, although two clones were isolated that responded only to MV antigens presented by autologous cells. Ten of 11 clones recognizing the nucleocapsid antigen were DR1-restricted, while the haemagglutinin antigen and whole measles virions were recognized more often in association with the DR2 antigen. These results indicate that much of the MV-specific memory T cell response is specific for the haemagglutinin and nucleocapsid virus antigens, with the DR antigen being the main restriction element involved.

Adult↗
PubMed1990

Lack of association of T cell receptor beta-chain constant region polymorphism with insulin-dependent diabetes mellitus in Finland.

Allelic polymorphism in the T cell receptor constant beta-chain gene region has been reported to be associated with autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). The present analysis of 164 children and adolescents with IDDM and 193 controls for BqlII polymorphism using a TcR-C beta cDNA probe revealed two allelic restriction fragments with sizes of 10.5 kb (U) and 9.6 kb (L). No particular association was observed between the RFLP genotypes and IDDM (UU 27% versus 31%; UL 53% versus 52%; and LL 20% versus 17%, in diabetic subjects and controls, respectively), nor were any differences found between patients with various HLA risk antigens. The frequency of heterozygotes was 52% in 63 DR3-positive diabetic subjects and 53% in 73 DR3-negative ones. The results do not support any involvement of the TcR constant region genes in susceptibility to IDDM.

Adolescent↗
PubMed1990

T-lymphocyte subsets defined by double immunofluorescence in multiple sclerosis.

T-lymphocyte subpopulations were studied in the blood of 25 multiple sclerosis patients and 25 healthy age and sex-matched controls. Monoclonal antibodies labelled with different fluorochromes were used to define the percentages of CD4 (helper/inducer) and CD8 (suppressor/cytotoxic) positive cells and to dissect them into phenotypic subgroups. The results confirm the decrease in CD8 positive cells in the blood associated with multiple sclerosis. The subset showing the most marked decrease was the CD11 marker negative population, which has been reported to be associated with cytotoxicity rather than suppression. There was no significant decrease in the percentage of cells positive for both CD4 and CD45R markers reported to contain suppressor-inducer or naive T-helper cells in the MS patients. The results suggest that further dissection of T-cell subpopulations may clarify our understanding of this disease process.

Adult↗
PubMed1990

HLA-DR antigens and HLA-DQ beta chain polymorphism in susceptibility to rheumatoid arthritis.

Forty four patients with rheumatoid arthritis (RA) were studied for HLA-DR antigens and for HLA-DQ beta chain gene restriction fragment length polymorphism using DNA hybridisation. A significant increase in the prevalence of the DR4 antigen and a tendency towards an increase of DR1 was found in patients with RA. No allelic form of HLA-DQ restriction fragment length polymorphism patterns was increased, but the prevalence of an allele characterised by a combination of 7.5 and 3 kb fragments was decreased among patients with RA. The DQw8 subtype represented by a 12 kb fragment was the most common DR4 associated allele, and a 3.7 kb fragment related to DQw7 was found in only 5/25 (20%) DR4 positive patients and 2/12 (17%) controls. The results support the hypothesis that RA susceptibility factors are primarily located within HLA-DR genes but HLA-DQ genes may have a role in protection from the disease.

Arthritis, Rheumatoid↗
PubMed1990

Analysis of impaired in vitro immunoglobulin synthesis in rheumatoid arthritis.

Decreased immunoglobulin production in pokeweed mitogen driven lymphocyte cultures has been reported in rheumatoid arthritis (RA). Here various activators and experimental designs have been used to determine the contribution of B cells, T cells, or monocytes to this low response. Sixty patients with RA and paired controls were studied at the onset of disease and again six months later. Concentrations of IgA, IgG, and IgM in cultures of RA peripheral blood mononuclear cells stimulated with thymus dependent activators were already decreased at the onset of the disease. Six months later RA mononuclear cells produced even lower concentrations of immunoglobulin. In contrast, stimulation with a T cell independent activator showed that RA B lymphocytes had retained normal potential to synthesise immunoglobulin. Poor helper function was indicated by costimulation experiments and cultures of mixed mononuclear cells from patients and controls. This notion was supported also by the fact that phytohaemagglutinin induced interleukin-2 production by RA mononuclear cells was less than half of the control values. Nonspecific suppressor activity was similar in RA and controls. Monocyte functions were normal when tested by addition of indomethacin or 2-mercaptoethanol to the mitogen activated cultures. The defect in mitogen stimulated immunoglobulin production in vitro of RA mononuclear cells thus was more pronounced with time and probably reflects impaired mediator associated help in the differentiation of B lymphocytes into immunoglobulin secreting cells.

Adolescent↗
PubMed1989

A comparison of childhood and adult type I diabetes mellitus.

The incidence rate of insulin-dependent (Type I) diabetes mellitus is bimodal: one peak occurs close to puberty, and the other in the fifth decade. To evaluate possible differences in these forms of the disease, we examined the clinical, biochemical, autoimmune, and genetic features of 82 children and adolescents (1.3 to 18.2 years old) and 44 adults (20.0 to 55.8 years old) when they presented with Type I diabetes. The mean (+/- SEM) duration of symptoms before diagnosis was longer in the adults (7.5 +/- 1.0 vs. 3.9 +/- 0.4 weeks; P less than 0.001), and their serum C-peptide concentrations at diagnosis were higher (0.29 +/- 0.03 vs. 0.17 +/- 0.01 nmol per liter; P less than 0.001), suggesting that they had more residual beta-cell function. There were no significant differences between the two groups in sex ratio, blood glucose levels, hemoglobin A1 values, degree of metabolic decompensation, or frequency of Type I diabetes in first-degree relatives. Thirty-four of 80 children tested (42.5 percent) were positive for insulin autoantibodies, as compared with only 1 of 26 adults (3.8 percent; P less than 0.001). However, the frequencies of islet-cell autoantibodies were similar in the adults and children (conventional autoantibodies, both 81 percent; complement-fixing autoantibodies, 46.2 percent and 60 percent). More children than adults were heterozygous for both HLA-Dw3/4 antigens (26.6 percent vs. 9.8 percent; P less than 0.05) and HLA-DR3/4 antigens (36.6 percent vs. 12.5 percent; P less than 0.05). We conclude that Type I diabetes that begins in adulthood is characterized by a longer symptomatic period before diagnosis, better preservation of residual beta-cell function, and lower frequencies of insulin autoantibodies and HLA-D3/D4 heterozygosity than Type I diabetes that begins in childhood or adolescence.

Adolescent↗
PubMed1989

Lymphocyte subsets in the cerebrospinal fluid in active multiple sclerosis.

We studied the relative number of lymphocyte subsets in the cerebrospinal fluid (CSF) of patients with active multiple sclerosis. The cells were double-labeled with monoclonal antibodies and were studied using a fluorescence-activated cell analyzer. The number of Leu2+Leu15+ cells and Leu3+Leu18+ cells was markedly reduced in the CSF but not in the peripheral blood of the patients. The number of Leu3+Leu18+ cells was reduced also in the CSF of control patients (patients with other inflammatory or infectious neurological diseases).

Flow Cytometry↗
PubMed1989

Production of viral antibodies in vitro by CSF cells from mumps meningitis and multiple sclerosis patients.

Cerebrospinal fluid (CSF) cells from 4 mumps meningitis and 11 multiple sclerosis (MS) patients were cultured in vitro for 7 days with and without pokeweed mitogen (PWM) stimulation. The cells produced varying amounts of IgG without stimulation and no significant increase of IgG synthesis was observed after PWM stimulation. Antibodies against mumps, measles, rubella, herpes simplex, and adeno viruses were measured in the supernatants of the cultures by a sensitive enzyme immunoassay. In the mumps meningitis patients, the largest amount of antibody was against mumps virus but low amounts of antibodies with other specificities were also synthesized by CSF cells of one patient. The most commonly detected specificities in MS patients were against measles and rubella viruses, whereas antibodies against adeno and mumps viruses were detected in only one CSF cell supernatant. No antibodies produced against herpes simplex virus in vitro were detected in any of the supernatants. The amounts of viral antibodies produced in vitro and intrathecally were only partially correlated.

Antibodies, Viral↗
PubMed1989

Francisella tularensis-specific T-cell clones are human leukocyte antigen class II restricted, secrete interleukin-2 and gamma interferon, and induce immunoglobulin production.

T-cell clones (TLC) were established from a Francisella tularensis-vaccinated subject in order to study the cells responsive for cell-mediated immunity against F. tularensis. All the clones were human leukocyte antigen (HLA) class II restricted to one of the HLA-DR specificities of the original donor. The TLC cells were CD4+ and produced interleukin-2 and gamma interferon after stimulation with specific antigen. Seven of the eight clones tested assisted in the production of immunoglobulin G (IgG), IgA, and IgM antibodies.

Clone Cells↗
PubMed1989

Infection of human peripheral blood mononuclear cells with a temperature-sensitive mutant of measles virus.

A stable temperature-sensitive mutant of measles virus (MV ts38) was used to study the mechanism of virus-mediated immune suppression of peripheral blood mononuclear cells in vitro. Both unstimulated and phytohemagglutinin-stimulated cultures released infectious virus at 32 degrees C, whereas no virus was released at 37 degrees C, although both viral RNA and viral proteins were synthesized. However, the response of the lymphoid cells to phytohemagglutinin, concanavalin A, and herpes simplex virus antigen was decreased in the presence of MV ts38 at 37 degrees C. The viability of infected cells was not diminished, therefore excluding cell death as a reason for immunosuppression. Interleukin 2 did not play a role in the inhibitory effect of MV ts38. Antibodies to alpha interferon partially reversed the inhibitory effect of the virus infection on lymphocyte mitogenesis, thus implying that alpha interferon plays a role in the immunosuppression. Depletion experiments indicated that adherent cells play a greater role in the measles virus-induced immunosuppression than nonadherent cells. However, monocyte maturation to macrophages had no effect on the degree of immunosuppression.

Cell Differentiation↗
PubMed1989

Low levels of mumps virus antigen induced interferon-alpha production in insulin-dependent diabetes.

The in vitro production of interferon-alpha was studied in cultures of peripheral blood mononuclear cells from children with insulin-dependent diabetes. Significantly lower levels (p less than 0.01) of interferon (median 64 IU/ml) were found in mumps antigen stimulated cultures of IDDM patients compared to control children (median 256 IU/ml) whereas no differences between groups were found in the amount of interferon induced by Coxsackie B pool antigen or live Sendai virus.

Antigens, Viral↗
PubMed1989

Measles virus inhibits lymphocyte proliferation in vitro by two different mechanisms.

We studied the effect of two different strains of measles virus (MV) on the lymphocyte blast transformation response. Infectious virus inhibited the proliferation response to PHA early during the culture when freshly isolated PBMC were stimulated. However, MV stimulated the proliferation of T cell lines early after infection and the inhibition was a late phenomenon associated with cell death. The early inhibition by the Edmonston strain of MV was shown to be monocyte-dependent by depletion studies with monoclonal antibodies. It could be partially explained by IFN-alpha production as the addition of anti-IFN-alpha antiserum to the cultures reversed the virus-induced inhibition and the addition of IFN reduced the response of uninfected PBMC. The late inhibition by the Edmonston strain was associated neither with monocytes nor with IFN-alpha but correlated with cell death in cultures. The inhibition by the Halle strain of MV was strong and associated with cell death already early after infection. The results demonstrate that MV inhibits lymphocyte proliferation by two different mechanisms and different virus strains vary both in the magnitude and mechanism of inhibition.

Cell Line↗
PubMed1988

Impaired interleukin 1 and interleukin 2 production following in vitro abortive infection of murine spleen mononuclear cells by Semliki Forest virus.

The effect of Semliki Forest virus (SFV) infection of murine spleen mononuclear cells was investigated in vitro. A small percentage of spleen macrophages expressed viral antigens, but no infectious virus particles were released, indicating an abortive-type infection. Wild-type SFV infected a higher percentage of macrophages than the attenuated, demyelinating mutant A7. The proliferation of spleen mononuclear cells under Con A stimulation was inhibited by the viral infection. The supernatant (SN) harvested from infected and Con A-stimulated spleen adherent cells could not stimulate thymocytes in an interleukin 1 (IL-1) assay and indomethacin treatment of infected cultures had no effect. The stimulatory effect of SN from noninfected cultures in the IL-1 assay was reduced when SN from infected cultures was added, suggesting the presence of an IL-1 inhibitor. Interleukin 2 (IL-2) production by splenocytes also decreased after viral infection, but exogenous IL-2 restored the response to Con A stimulation of infected spleen cells. This study demonstrates that abortive SFV infection of spleen macrophages has an immunosuppressive effect which may lead to an aberrant immune regulation.

Animals↗
PubMed1988

Relationship between serum insulin autoantibodies, islet cell antibodies and Coxsackie-B4 and mumps virus-specific antibodies at the clinical manifestation of type 1 (insulin-dependent) diabetes.

In order to elucidate the possible relationship between insulin autoantibodies (IAA), conventional (ICA-IgG) and complement-fixing (CF-ICA) islet cell antibodies and Coxsackie-B4 and mumps virus-specific antibodies (IgG, IgM and IgA classes), we studied 194 children and adolescents with newly diagnosed Type 1 (insulin-dependent) diabetes. Sixty-one (31.4%) of the subjects were IAA-positive at diagnosis and 73.8% (45/61) of these also had ICA-IgG compared to 51.1% (68/113, p less than 0.01) of IAA-negative children. CF-ICA showed no significant association with IAA. The levels of IAA were significantly higher in the patients with ICA-IgG compared to those without [5.9 +/- 1.6% (SEM) vs 2.5 +/- 0.3%, p less than 0.01]. The patients positive for IAA were younger at diagnosis than the IAA-negative ones; (7.1 +/- 0.5 vs 9.3 +/- 0.3 years, p less than 0.001) and this was also true for ICA-IgG-positive children (8.1 +/- 0.4 vs 9.4 +/- 0.5 years, p less than 0.05) in comparison to ICA-IgG-negative subjects. No significant associations were found between IAA or ICA on the one hand and a positive family history of Type 1 diabetes or metabolic derangements at diagnosis on the other. Subjects negative for ICA were more frequently positive for mumps virus specific IgG antibodies than the ICA-positive patients (50/80 vs 53/111, p less than 0.05), and Coxsackie-B4 virus-specific IgA antibodies were more common in the CF-ICA-negative than the CF-ICA-positive children (53/111 vs 29/80, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗