Biomedical subjects

Riitta Karttunen

Publications and source records attributed to Riitta Karttunen.

7 recordsLinked to original sources

PubMed2005

Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica.

Intervertebral disc disease (IDD) characterized by sciatica is a common disorder affecting about 5% of individuals. Environmental factors can predispose to this disease, but IDD has a strong genetic background. Recent evidence suggests that inflammation is one of the key factors in the etiology of IDD. Here, a possible role of the inflammatory mediator genes was studied in 155 patients with IDD-related sciatica and 179 controls. Forty-eight patients were analyzed for mutations in the IL1A, IL1B, IL6 and TNFA genes, and 16 polymorphisms in 10 candidate cytokine genes (IL1A, IL1B, IL1RN, TNFA, IL2, IL4, IL4R, IL6, IL10, IFNG) were genotyped from all subjects. No disease-causing mutations were identified in IL1A, IL1B, IL6 or TNFA. Allele frequencies were, however, significantly different between the two groups for IL6 SNP, T15A in exon 5 (P=0.007). Furthermore, the genotypes AA and AT of the exon 5 SNP were more common in the patients (P=0.011; OR=4.4, 95% CI=1.2-15.7; AR=7.5%, 1.6-13.1%). Haplotypes were then generated for four IL6 SNPs, G-597A, G-572C, G-174C, and T15A in exon 5. Haplotype GGGA was more common in the patients (P=0.011; OR=4.8, 95% CI=1.6-14.5). To evaluate attributable risk, haplotype pairs were assigned for the individuals. The presence of GGGA/GGGA or GGGA/other genotypes had an OR of 5.4 (95% CI=1.5-19.2). Association of GGGA with disease was highly significant (P=0.0033), and the associated AR was 6.8% (1.9-11.5%). These findings support the role of IL-6 genetic variations in discogenic pain.

Adult↗

PubMed2005

Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease.

BACKGROUND: Cow's milk protein sensitive enteropathy (CMSE) and celiac disease (CD) associate with upregulation of local intestinal immune responses, including activation of cytotoxic lymphocytes. OBJECTIVE: We investigated whether this upregulation can be detected at the systemic level by analyzing serum concentrations of granzymes A (GrA) and B (GrB), soluble Fas, and CD30. METHODS: Fifty-seven children with a final diagnosis of CMSE in 23 subjects (18 untreated and 5 on a diet), 20 untreated CD patients, and 14 control subjects with no gastrointestinal disease were examined by endoscopy for gastrointestinal complaints. Duodenal biopsies were studied for basic histology, CD3, alphabeta and gammadelta T-cell receptors (TCRs), and serum samples by commercial ELISA assays. RESULTS: Concentrations of GrA and GrB were significantly higher in untreated CMSE and in CD as compared with the control subjects. Measurable GrB was present in only 20% of the control subjects but in 100% of patients with CMSE. CD30 was similarly increased in both untreated CMSE and CD cases, whereas in treated CMSE cases the concentrations were equal to the control subjects. All groups showed similar soluble Fas. The numbers of duodenal CD3 + , alphabeta- and gammadelta-TCRs correlated with the serum granzyme and CD30 levels. CONCLUSION: The intestinal immune response in CMSE and CD is manifested by the increase in serum GrA, GrB, and CD30; the measurement of these markers provides a new practical and objective complementary means for diagnosis and assessment of treatment response. However, this has to be confirmed by more studies before routine use.

Adolescent↗

PubMed2005

Increased IFN-gamma secretion from duodenal biopsy samples in delayed-type cow's milk allergy.

A delayed and local gastrointestinal hypersensitivity to cow's milk (CM) protein is difficult to diagnose and there are limited data on this disorder. The aim of this study was to investigate local intestinal cytokine secretion in the upper small intestine in children with delayed-type cow's milk allergy (CMA). Duodenal biopsy samples from 31 children with delayed CMA, 14 with celiac disease (CD), and 14 healthy controls were studied for the spontaneous release of IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, and IL-10, measured by cytometric bead array, and of TGF-beta and IL-6 measured by ELISA. The children with delayed CMA secreted more IFN-gamma than the controls (p = 0.006) and the children with CD (p = 0.006). The children with CD secreted more IL-6 compared to the controls (p = 0.008) and the children with delayed CMA (p = 0.002). The children with delayed CMA who had continuously been exposed to CM secreted less TGF-beta than the children with delayed CMA who avoided CM (p = 0.050), and showed a tendency towards lower secretion compared to the controls (p = 0.078). Secretions of TNF-alpha, IL-2, IL-4, IL-5, and IL-10 were low in general; however, the children with delayed CMA who did not avoid CM secreted more IL-4 and IL-10 than the controls (p = 0.016, 0.059). In conclusion, the children with delayed CMA showed up-regulation of IFN-gamma. Interestingly, TGF-beta secretion was up-regulated in those children with delayed CMA who avoided CM suggesting recovery of regulation mechanisms.

Adolescent↗

PubMed2004

BCG vaccine modulates intestinal and systemic response to beta-lactoglobulin.

Beta-Lactoglobulin (BLG) is a clinically important antigen in cow's milk and one of the major allergens causing cow's milk allergy. Bacillus Calmette-Guerin (BCG) vaccination has been suggested to modify immune response possibly decreasing the risk of allergy to some antigens in both human and experimental animals. In the present study, we have analyzed whether the early BCG vaccination has any effect on the markers of systemic and gastrointestinal (GI) sensitization to BLG. We immunized two groups of Hooded-Lister rat puppets with intraperitoneal injections of native BLG at 43 and 62 days with pertussis vaccine as adjuvant, one group receiving additionally BCG. The animals were then fed native and denatured milk products twice weekly from 73 to 131 days of age, when they were killed. Control group was not vaccinated and received normal rat forage. Total immunoglobulin E (IgE) levels and BLG-specific IgG(1) and IgG(2a) concentrations were determined in serum samples. Spontaneous interleukin (IL)-4 and interferon (IFN)-gamma production from duodenal specimens were measured, and the inflammatory cells were quantitated in specimens from different sections of the GI tract. Administration of BCG simultaneously with BLG resulted in reduced IgE concentration in serum, while the specific IgG(1) and IgG(2a) antibody responses and the spontaneous secretion of IL-4 and IFN-gamma were not affected. Furthermore, BCG-induced eosinophilic infiltration and increase of intraepithelial lymphocytes (IEL) in the GI mucosa, and a trend toward increased number of lamina propria mononuclear inflammatory cells in the colon (BCG compared with BLG, p = 0.09; BCG compared with controls, p = 0.02). Controls showed increment of IgG(1) response in comparison with the BLG group (p = 0.04) and increase of mucosal eosinophilic infiltration. The BCG modified the response to BLG both at the systemic level as shown by decrease of total IgE and at GI mucosa where increase of eosinophilic infiltration and increased number of IEL were seen. Increment of IgG(1) level and eosinophils in the controls might be related with the lack of modulatory effect of pertussis vaccination. A shift of response toward the lower GI tract after BCG immunization as shown by a trend for increase of mononuclear inflammatory cells in colon lamina propria mimics disease development in some cases of clinical food allergy, and emphasizes the need for evaluation of the changes in the whole GI tract in food allergy models.

Animals↗

PubMed2003

Searching for links between endotoxin exposure and pregnancy loss: CD14 polymorphism in idiopathic recurrent miscarriage.

PROBLEM: Lipopolysaccharide (LPS) (endotoxin) is a well-known inducer of abortions in mice. In addition it has been proposed that gut-derived LPS of gram-negative bacteria may play a role in triggering idiopathic recurrent miscarriage (IRM) in humans. CD14 is one of the key molecules that mediates the effects of LPS. Promoter region polymorphism (-159C/T) in the CD14 gene is functionally important by regulating CD14 levels. High-producing CD14 genotype (TT) associates with deleterious effects of gut-derived LPS in hepatic cirrhosis in humans. It is not known whether women with IRM are genetically more prone to suffer from toxic effects of LPS. METHOD OF STUDY: By using polymerase chain reaction we analyzed the CD14 promoter region polymorphism in 38 women with IRM and in 127 normal controls of Finnish origin. RESULTS: There were no significant differences in the CD14 (-159C/T) allele or the genotype frequencies between the IRM women and the controls. However, there was a trend associating the presence of the T allele with increased odds of miscarriage. CONCLUSIONS: Although we were not able to find a statistically significant association between CD14 genotypes and IRM in our relatively small study population, a further study with a larger sample size is warranted to explore the role of high-producing CD14 genotypes in IRM. Also studies highlighting environmental LPS triggers and other intrinsic mediators of LPS signalling are needed to solve the enigmatic role of LPS in IRM in humans.

Abortion, Habitual↗

PubMed2002

Chlamydial heat shock protein 60--specific T cells in inflamed salpingeal tissue.

OBJECTIVE: To evaluate the role of chlamydial heat shock protein 60 (CHSP60)-specific T-lymphocytes in tubal factor infertility. DESIGN: Case series of patients with tubal factor infertility. SETTING: Infertility Clinic, Department of Obstetrics and Gynecology, Helsinki University Central Hospital and Laboratory of Cell-Mediated Immunity, National Public Health Institute, Oulu, Finland. PATIENT(S): Five patients with tubal factor infertility who underwent elective salpingectomy because of hydrosalpinges. INTERVENTION: Collection of salpingeal tissue specimens for in vitro culture of T-lymphocytes. MAIN OUTCOME MEASURE(S): Cloning of Chlamydia trachomatis and CHSP60-specific T-lymphocyte lines derived from inflamed salpingeal tissue. Cytokine production analysis of the established T-lymphocyte clones. RESULT(S): Seventy-seven (34%) of the 229 T-lymphocyte clones recognized C. trachomatis and C. pneumoniae elementary bodies as target antigens. One-third of these Chlamydia genus-specific T-lymphocyte clones further recognized CHSP60 as the target antigen. Most of the CHSP60-specific T-lymphocyte clones produced predominantly IL-10. CONCLUSION(S): CHSP60 may be an important T-lymphocyte antigen involved in the immunopathogenesis of tubal damage associated with chronic C. trachomatis infection.

Adult↗

PubMed2002

Effect of heat denaturation on beta-lactoglobulin-induced gastrointestinal sensitization in rats: denatured betaLG induces a more intensive local immunologic response than native betaLG.

Beta-lactoglobulin (betaLG) is one of the first foreign antigens encountered by a newborn child, and it is the major allergen causing cow's milk allergy. Heat denaturation causes changes to the protein structure, but the significance of heat-induced changes for immunogenicity or allergenicity is not known. To clarify how heat denaturation affects allergenicity and immunogenicity, we immunized Hooded-Lister rat pups with intra-peritoneal injections of native or heat-denatured betaLG at days 43 and 62 after birth. The animals were then fed native and denatured milk products twice weekly from 73 to 101 days of age with a feeding tube, after which they were allowed cheese and milk ad libitum, until they were killed on day 131. Total immunoglobulin (Ig)E and betaLG-specific IgG1 and IgG2a levels were determined from serum samples. Spontaneous interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) production was measured from duodenal specimens, and specimens of gastrointestinal mucosae were studied for the presence of inflammatory cells. The rats immunized with native betaLG had higher levels of total serum IgE than the unimmunized controls or the rats immunized with heat-denatured betaLG, while heat-denatured betaLG induced a significantly more intensive mononuclear inflammatory cell and eosinophil infiltration in the gastroduodenal mucosa. The betaLG-specific IgG antibody and IL-4 and IFN-gamma responses were similar in the two groups of immunized animals. Hence, denaturation modifies the immunogenic and allergenic properties of betaLG. Heat-denatured betaLG induces a more intensive local reaction in the gastrointestinal mucosa, while there is some evidence for enhanced systemic allergic sensitization by native betaLG.

Animals↗