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T Klemola

Publications and source records attributed to T Klemola.

At least 19 recordsLinked to original sources
PubMed2001

Wheat omega-5 gliadin is a major allergen in children with immediate allergy to ingested wheat.

BACKGROUND: Sensitization to wheat by ingestion can lead to food allergy symptoms and wheat-dependent, exercise-induced anaphylaxis. Sensitization by inhalation causes bakers' asthma and rhinitis. Wheat allergens have been characterized at the molecular level in bakers' asthma and in wheat-dependent, exercise-induced anaphylaxis, in which omega-5 gliadin (Tri a 19) is a major allergen. However, little information is available regarding allergens responsible for hypersensitivity reactions to ingested wheat in children. OBJECTIVE: The aim of this study was to examine whether children with allergy to ingested wheat have IgE antibodies to omega-5 gliadin. METHODS: Sera were obtained from 40 children (mean age, 2.5 years; range, 0.7-8.2 years) with suspected wheat allergy who presented with atopic dermatitis and/or gastrointestinal and/or respiratory symptoms. Wheat allergy was diagnosed with open or double-blinded, placebo-controlled oral wheat challenge. Wheat omega-5 gliadin was purified by reversed-phase chromatography, and serum IgE antibodies to omega-5 gliadin were measured by means of ELISA. In vivo reactivity was studied by skin prick testing. Control sera were obtained from 22 children with no evidence of food allergies. RESULTS: In oral wheat challenge, 19 children (48%) reacted with immediate and 8 children (20%) with delayed hypersensitivity symptoms. Sixteen (84%) of the children with immediate symptoms had IgE antibodies to purified omega-5 gliadin in ELISA. In contrast, IgE antibodies to omega-5 gliadin were not detected in any of the children with delayed or negative challenge test results or in the control children. The diagnostic specificity and positive predictive value of omega-5 gliadin ELISA were each 100% for immediate challenge reactions. Skin prick testing with omega-5 gliadin was positive in 6 of 7 children with immediate challenge symptoms and negative in 2 children with delayed challenge symptoms. CONCLUSION: The results of this study show that omega-5 gliadin is a significant allergen in young children with immediate allergic reactions to ingested wheat. IgE testing with omega-5 gliadin could be used to reduce the need for oral wheat challenges in children.

Allergens↗
PubMed2000

Experimental tests of predation and food hypotheses for population cycles of voles.

Pronounced population cycles are characteristic of many herbivorous small mammals in northern latitudes. Although delayed density-dependent effects of predation and food shortage are often proposed as factors driving population cycles, firm evidence for causality is rare because sufficiently replicated, large-scale field experiments are lacking. We conducted two experiments on Microtus voles in four large predator-proof enclosures and four unfenced control areas in western Finland. Predator exclusion induced rapid population growth and increased the peak abundance of voles over 20-fold until the enclosed populations crashed during the second winter due to food shortage. Thereafter, voles introduced to enclosures which had suffered heavy grazing increased to higher densities than voles in previously ungrazed control areas which were exposed to predators. We concluded that predation inhibits an increase in vole populations until predation pressure declines, thus maintaining the low phase of the cycle, but also that population cycles in voles are not primarily driven by plant-herbivore interactions.

Animals↗
PubMed2000

Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease.

The hematopoietic-specific transmembrane protein tyrosine phosphatase CD45 functions to regulate Src kinases required for T- and B-cell antigen receptor signal transduction. So far, there have been no reports to our knowledge of a human deficiency in a tyrosine-specific phosphatase. Here, we identified a male patient with a deficiency in CD45 due to a large deletion at one allele and a point mutation at the other. The point mutation resulted in the alteration of intervening sequence 13 donor splice site. The patient presented at 2 months of age with severe combined immunodeficiency disease. The population of peripheral blood T lymphocytes was greatly diminished and unresponsive to mitogen stimulation. Despite normal B-lymphocyte numbers, serum immunoglobulin levels decreased with age. Thus, CD45 deficiency in humans results in T- and B-lymphocyte dysfunction.

Antigens, CD↗
PubMed1997

Mutation pattern in the Bruton's tyrosine kinase gene in 26 unrelated patients with X-linked agammaglobulinemia.

Mutation pattern was characterized in the Bruton's tyrosine kinase gene (BTK) in 26 patients with X-linked agammaglobulinemia, the first described immunoglobulin deficiency, and was related to BTK expression. A total of 24 different mutations were identified. Most BTK mutations were found to result in premature termination of the translation product. Mutations were detected in most BTK exons with a predominance of frameshift and nonsense mutations in the 5' end of the gene and missense mutations in its 3' part, corresponding to the catalytic domain of the enzyme. Nonsense and frameshift mutations were associated with diminished levels of BTK mRNA expression, except for a frameshift mutation in exon 17 and two nonsense mutations in exon 2, indicating that these cases are not confined to penultimate exons. One amino acid substitution (R28H) was found in the pleckstrin homology domain's residue, which is mutated in mice bearing the X-linked immunodeficiency phenotype; another substitution (R307G) was identified in the src homology domain 2. All remaining amino acid substitutions were found in the catalytic domain of Btk.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1997

Clinical spectrum of X-linked hyper-IgM syndrome.

We report the clinical and immunologic features and outcome in 56 patients with X-linked hyper-IgM syndrome, a disorder caused by mutations in the CD40 ligand gene. Upper and lower respiratory tract infections (the latter frequently caused by Pneumocystis carinii), chronic diarrhea, and liver involvement (both often associated with Cryptosporidium infection) were common. Many patients had chronic neutropenia associated with oral and rectal ulcers. The marked prevalence of infections caused by intracellular pathogens suggests some degree of impairment of cell-mediated immunity. Although lymphocyte counts and in vitro proliferation to mitogens were normal, a defective in vitro proliferative response to antigens was observed in some patients, and additional defects of cell-mediated immunity may be presumed on the basis of current knowledge of CD40-ligand function. All patients received regular infusions of immunoglobulins. Four patients underwent liver transplantation because of sclerosing cholangitis, which relapsed in there. Three patients underwent bone marrow transplantation. Thirteen patients (23%) died of infection and/or liver disease. X-linked hyper-IgM syndrome, once considered a clinical variant of hypogammaglobulinemia, is a severe immunodeficiency with significant cellular involvement and a high mortality rate.

Bone Marrow Transplantation↗
PubMed1997

Density of gamma/delta+ T cells in the jejunal epithelium of patients with coeliac disease and dermatitis herpetiformis is increased with age.

Increased density of gamma/delta T cell receptor (TCR)+ intraepithelial lymphocytes is the only characteristic in the jejunum of patients with coeliac disease and dermatitis herpetiformis which is not normalized on a gluten-free diet. We explored the age-dependent changes in intraepithelial gamma/delta and alpha/beta TCR+ cells from 137 biopsies from patients with coeliac disease and dermatitis herpetiformis and from controls. Biopsy specimens from 100 patients with coeliac disease and dermatitis herpetiformis and from 37 controls were studied with an immunohistochemical method using MoAbs to T cell receptors and peroxidase staining. An increase in the density of intraepithelial gamma/delta T cells above the mean +2 s.d. of the density in controls was present in 97 of 100 specimens from patients with coeliac disease and dermatitis herpetiformis. The density of gamma/delta+ cells of patients with coeliac disease and dermatitis herpetiformis on a normal gluten-containing diet showed a positive correlation with age (r = 0.45, P < 0.0001). In controls, the density of gamma/delta+ cells remained low throughout the age-range studies, from age 0.6-57 years. In controls, alpha/beta+ cells increased with age (r = 0.57, P < 0.001). The increase in density of intraepithelial lymphocytes with age is in agreement with their thymus-independent character and local proliferation.

Adolescent↗
PubMed1995

Development of immune response to cow's milk proteins in infants receiving cow's milk or hydrolyzed formula.

BACKGROUND: Development of humoral and cellular immune responses to orally administered antigens in human beings is poorly understood, although antigen administration has been suggested as a treatment for hypersensitivity disorders and autoimmune diseases. OBJECTIVE: The purpose of the study was to investigate the development of systemic immune response in infants fed with formula containing whole cow's milk proteins or hydrolyzed formula containing casein peptides. METHODS: In a double-blind trial, 10 infants received cow's milk-based formula, and 10 infants received a casein hydrolysate formula until the age of 9 months. Blood samples were taken at the ages of 6, 9, and 12 months. Cellular responses were assessed by proliferation assay of peripheral blood mononuclear cells to cow's milk proteins (beta-lactoglobulin, bovine serum albumin, and alpha-casein). Humoral responses to the same proteins were measured by ELISA for IgG antibodies. RESULTS: Feeding infants with cow's milk-based formula induced systemic humoral and cellular responses to cow's milk proteins. T-cell response later declined, supporting the concept of oral tolerization. Exposure to cow's milk proteins after the age of 9 months resulted in depressed cellular and humoral responsiveness to these proteins. CONCLUSION: Our results support the view that induction of oral tolerance in human beings is an age-dependent phenomenon.

Animals↗
PubMed1995

Immunohistochemical findings in jejunal specimens from patients with IgA deficiency.

Jejunal biopsy specimens from 25 patients with IgA deficiency (IgAd) were studied immunohistochemically to find markers of inflammation. Five of the 25 patients had coeliac disease (CD): they were on a gluten free diet and had normal jejunal morphology. Only two of 15 specimens from control subjects had CD25+ cells in the surface epithelium, while this was seen in 19 out of 20 specimens from IgAd patients (p < 0.0001). A significant increase of CD25+ cells was also noted in the lamina propria of IgAd patients. The median percentage of crypt cells in mitosis (Ki67+ cells) was higher in the specimens from IgAd patients (26%) than in those from controls (13%, p < 0.001). The densities of gamma delta T cell receptor positive cells in the surface epithelium and lamina propria did not differ in the specimens from IgAd patients and those of controls nor was the expression of HLA class II antigens augmented in the surface epithelium. These findings were similar for the IgAd patients whether or not the patient had DQB 0201 allele, a genetic marker which is strongly associated with CD. The inadequacy of the local immunoglobulins in patients with IgAd may lead to increased T cell activation, which is accompanied by the appearance of intraepithelial CD25+ cells and with an increase in the mitotic rate in the crypts.

Biomarkers↗
PubMed1994

Peripheral gamma delta T cell receptor-bearing lymphocytes are increased in children with celiac disease.

The percentages of gamma delta T cell receptor-bearing (TCR+) cells in the peripheral blood and jejunal mucosa of patients with celiac disease were measured before treatment, during a gluten free-diet, and after a gluten challenge. The percentages of the different cell types were evaluated by flow cytometry, and immunohistochemical staining of the jejunal specimen was used to identify lymphocyte surface markers. Nineteen blood samples and intestinal specimens from 13 children with celiac disease (eight samples taken before treatment, six during gluten-free diet, and five after gluten challenge) and samples from nine controls were studied. The proportion of gamma delta TCR+ lymphocytes was significantly higher both in the peripheral blood and the jejunal mucosa of the patients with celiac disease. A significant correlation was found between the percentage of peripheral gamma delta TCR+ cells and the density of gamma delta TCR+ cells in the lamina propria.

Adolescent↗
PubMed1989

Immunohistochemical study of lymphoplasmacytic infiltrate and epithelial HLA-DR expression in the rectal and colonic mucosae of children with ulcerative colitis.

Lymphocyte subpopulations, plasma cells in the lamina propria, and the expression of HLA-DR antigens on the epithelium of the rectal and colonic mucosae were studied in eight children with ulcerative colitis and 12 control subjects using a panel of monoclonal antisera and the peroxidase technique before any treatment and 3 months later (four patients). The numbers of intraepithelial lymphocytes were similar in specimens from patients and controls. The majority of these cells (on average, 73% in the patients and 84% in the controls) were mature CD3+ T cells; among them, CD8+ suppressor-cytotoxic cells were preponderant. In both untreated and treated patients, the numbers of mature T cells in the rectal mucosae were supranormal (1,870 +/- 205 cells/mm2, p less than 0.01 and 1,537 +/- 214 cells/mm2, p less than 0.05, respectively; controls, 1,105 +/- 214 cells/mm2). In rectal specimens from untreated patients, the number of helper T (CD4+) cells was increased (1,094 +/- 74 versus 801 +/- 74 cells/mm2, p less than 0.05); the same specimens had more B-1-positive (CD20+) B cells and pre-B cells (122 +/- 21 versus 71 +/- 17 cells/mm2, p less than 0.05). The number of IgG-containing cells was significantly greater than in the controls (1,058 +/- 263 versus 359 +/- 64 cells/mm2, p less than 0.01), and the commonest isotype in the plasma cells of patients was IgG. The number of IgE-containing cells was also significantly elevated (230 +/- 40 versus 95 +/- 16 cells/mm2, p less than 0.01). The numbers of IgA- and IgM-containing cells were similar in patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Transient IgA and IgM deficiencies are frequent in children with ulcerative colitis.

Serum immunoglobulin levels in 22 children with ulcerative colitis were followed for 2 years after diagnosis of the disease. A statistically significant depression of IgA, IgM, and IgG was noticed; depression of IgA and IgM was most frequent. The depression of immunoglobulin levels was transient and was most prominent during the first year of treatment. All patients in the study received sulphasalazine. Disease activity or steroid medication had no influence on immunoglobulin levels. The development of immunoglobulin deficiencies was not connected with any HLA antigen; we found decreased frequency of antigen B7 in the whole group.

Adolescent↗
PubMed1988

Inadequacy of mucosal IgM antibodies in selective IgA deficiency: excretion of attenuated polio viruses is prolonged.

A nationwide vaccination campaign with oral poliovirus vaccine was organized in Finland in 1985 in order to cease an outbreak of poliomyelitis. We followed eight IgA-deficient individuals and nine controls for poliovirus excretion in feces and for antibody responses in serum and saliva. Five weeks after oral poliovirus vaccination all eight IgA-deficient individuals were still excreting polioviruses, in contrast to one of nine controls. The concentration of polioviruses, as estimated by a semi-quantitative immunofluorescent assay, was generally higher and the test was significantly more often positive in the samples from the IgA-deficient individuals. Although serum levels of antibodies to poliovirus type 3 were lower in IgA-deficient individuals before vaccination, both measurements showed that the two groups had similar antibody levels 4 weeks after vaccination. IgA-deficient individuals lacked salivary IgA antibodies to poliovirus types 1 and 3 but had increased levels of IgM antipolio antibodies, which were shown to carry secretory component. We conclude that the mucosal IgM antibodies of IgA-deficient individuals eliminate polioviruses less efficiently than do the IgA antibodies of normal individuals.

Adolescent↗
PubMed1988

HLA antigens in IgA deficient paediatric patients.

HLA antigens (A, B, C and DR loci) were studied in 62 IgA-deficient (IgAd) paediatric patients: 17 with coeliac disease (CD), 13 with juvenile arthritis (JA), 27 with frequent respiratory tract infections (RTI) and five with other diseases. The frequencies of HLA antigens in IgAd patients were compared with those in healthy blood donors, and in CD and JA patients with normal serum IgA levels. The IgA deficiency in the patients showed significant associations with HLA A1, B8, B13, Cw6, DR3 and DR7 (P less than 0.0005, P corr less than 0.02 vs controls) and decreased frequencies of DR2 (P less than 0.0005, P corr less than 0.02 vs controls). The HLA associations typical of coeliac disease, increased frequencies of HLA-B8 and DR3, were evident among the IgAd coeliacs; in contrast to the coeliacs with normal IgA levels, the IgAd coeliacs showed a significant increase of the HLA-Cw6 allele (P less than 0.0005, P corr less than 0.02 vs control coeliacs). Increased frequencies of HLA-A1, B8, B13, Cw6, DR3 and DR7 were noted in the patients with RTI, which can be explained by the frequent occurrence of the haplotypes A1, B8, DR3 and B13, DR7, the latter haplotype often also having the Cw6 allele. Among the IgAd JA patients, the antigen frequencies were similar to those in the JA patients with normal serum immunoglobulins.

Adolescent↗