M. Halttunen

Portfolios as a learning tool in obstetrics and gynaecology undergraduate training.

We developed a structured portfolio for medical students to use during their obstetrics and gynaecology undergraduate training. The main objective was to support the learning process of the students. We also wanted feedback information to enhance teaching.

Chlamydia trachomatis heat shock protein-60 induced interferon-γ and interleukin-10 production in infertile women

Chlamydia trachomatis‐associated tubal factor infertility (TFI) involves enhanced humoral and cell‐mediated immune response to the chlamydial 60 kDa heat shock protein (CHSP60). We evaluated the role of CHSP60‐induced immune response in TFI by studying lymphocyte proliferation and cytokine (interferon (IFN)‐γ, interleukin (IL)‐12 and IL‐10) secretion in response to C. trachomatis elementary body (EB) and CHSP60 antigens in 57 women with TFI and in 76 women with other causes of infertility. Positive proliferative response of PBMC to CHSP60 was more common in the TFI group (20/57; 36%) than in the other groups (17/76; 22%) although the frequency or the median responses did not differ significantly (1·6, range 0·2–22·1 versus 1·4; 0·2–24·4). C. trachomatis EB induced significantly higher IFN‐γ and lower IL‐10 secretion in the TFI group compared to the other groups. The EB and CHSP60 induced IL‐12 secretion was similar in all study groups and correlated with IFN‐γ secretion in the other but not in the TFI group. The lack of correlation between EB‐induced IL‐12 and IFN‐γ production and simultaneously found prominent IL‐10 secretion in response to CHSP60 in the TFI group suggests that the CHSP60 may have a specific role in regulating the immune reactions during chlamydial infection and may consequently contribute to the immunopathogenesis of TFI.

The role of Chlamydia trachomatis infection in male infertility

To study the association between plasma antibodies to Chlamydia trachomatis and male infertility, 90 men from infertile couples attending a University Hospital IVF clinic for IVF/intracytoplasmic sperm injection, and 190 healthy blood donors as control subjects were studied for IgG and IgA antibodies to C. trachomatis, and for the men from infertile couples seminal fluid analysis was performed according to the World Health Organization criteria. The prevalence of plasma IgG antibodies to C. trachomatis was higher among men from infertile couples than control men, and men with chlamydial antibodies had lower sperm counts than those without.

IL-10 polymorphism and cell-mediated immune response to Chlamydia trachomatis

Chlamydia trachomatis infection induces an inflammatory response that is crucial in resolving acute infection but may also play a key role in the pathogenesis of C trachomatis associated infertility. The immune response is linked to cytokine secretion pattern which is influenced by the host genetic background. To study a relationship between interleukin-10 (IL-10) promoter −1082 polymorphism and cell-mediated immune response during C trachomatis infection in vitro, lymphocyte proliferation and cytokine (IL-10, IFN-γ, TNF-α, IL-2, IL-4 and IL-5) secretion were analysed in subjects with different IL-10 genotypes. Enhanced IL-10 secretion and reduced antigen-specific lymphocyte proliferative and IFN-γ responses were found in subjects with IL-10 −1082 GG genotype when compared to those with −1082 AA genotype. CD14+ monocytes were main source of IL-10 indicating that these cells are important regulators of the antigen-specific cell-mediated responses during active C trachomatis infection. We conclude that impaired cell-mediated response to C trachomatis is associated with IL-10 genotype in subjects with high IL-10 producing capacity. A comparison of immune markers between subjects with a history of noncomplicated and complicated infection is needed to further understand the confounding factors associated with the development of C trachomatis associated sequelae.

Prerequisites for human papillomavirus vaccine trial: results of feasibility studies

BACKGROUND AND AIMS Oncogenic human papillomaviruses (HPVs) are the major cause of cervical cancer and associated cancers. First generation preventive vaccines against HPVs are entering clinical trials. Therefore, it is time to consider prerequisites of field trials in Finland. RESULTS Incidence of cervical cancer is increasing in young women which is not unexpected since risk taking behavior among young women has also increased. In the developed countries up to 44% of cervical cancer cases are attributable to HPV16 infection alone. However, high risk HPV types other than HPV16 and HPV18 are emerging in the population based on HPV DNA pilot screening studies. Annual attack rates among young women less than 25 years of age is 2.3% for HPV16 infection, and 0.03% for CIN3 invasive cervic cancer. Thus, sample size estimates for HPV vaccine efficacy trial are approximately 1000 when the endpoint is HPV16 infection, and approximately 15000 when the endpoint is >/=CIN3 or worse assuming that the vaccine efficacy is 70%. Both HPV vaccine trial acceptability and compliance rates at routine visits of the general Finnish female population are going to be high based on a pilot study. CONCLUSION Prerequisites for large scale field trials on HPV vaccination are fulfilled in Finland.

Cytokine gene polymorphism and Chlamydia trachomatis-specific immune responses.

Chlamydia trachomatis-induced fallopian tube damage leading to tubal factor infertility (TFI) is linked with TNF, IL-10, and probably IFNG gene polymorphisms. The aim of this study was to clarify the contribution of these cytokine gene polymorphisms to interindividual variation in C trachomatis-specific immune responses and the cross-regulation of secreted cytokines and single nucleotide polymorphisms (SNPs). Cytokine polymorphisms (IL-10 -1082A/G, -819T/C, and -592A/C, IFNG +874T/A, and TNF -308G/A) were genotyped by polymerase chain reaction in 139 women. C trachomatis-specific immune responses were measured using lymphocyte proliferation (LP) induced by C trachomatis E and F strains and chlamydial heat shock protein 60 antigens. Cytokine secretion was measured in culture supernatants of infected and uninfected mononuclear leukocytes. IL-10 -1082/-819/-592 and IFNG +874 SNPs were associated with the intensity of LP responses to C trachomatis antigens. These cytokines also interact with each other and a cumulative effect of IL-10 -1082 and IFNG +874 genotypes was seen in LP responses to C trachomatis antigens. Our data suggest that interleukin-10 and interferon-γ regulate C trachomatis-specific immune responses in humans and that genetic variation in the expression of their coding genes explains interindividual variation in host immune responses to C trachomatis infection.

Effect of IL12A and IL12B polymorphisms on the risk of Chlamydia trachomatis-induced tubal factor infertility and disease severity

BACKGROUND Interleukin-12 (IL-12) and related cytokines induce activation and differentiation of T cells. Our aim was to investigate the associations between genetic differences in IL-12-family cytokines and the pathogenesis of chlamydial disease. METHODS The final study population consisted of 100 women with Chlamydia trachomatis-induced tubal factor infertility (TFI) and 125 pregnant women as controls. Three single nucleotide polymorphisms (SNPs) of IL12A and seven SNPs of IL12B genes were determined from isolated DNA using the Sequenom system with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. RESULTS We found that the IL12B SNP rs3212227 was associated with both susceptibility and severity of TFI. The minor allele C was rare and only one CC homozygote was found among the controls. AC heterozygotes were more common among TFI cases than among controls (P = 0.009) and were associated with increased risk of TFI [odds ratios (OR) = 2.44, 95% confidence intervals (CI) = 1.23-4.87]. Carrying the minor allele C was also associated with disease severity (P for trend = 0.008) and moderate (OR = 2.51, 95% CI = 1.06-5.95) and severe tubal damage (OR = 2.73, 95% CI = 1.15-6.52). CONCLUSIONS The results suggest that variation in the IL12B gene partly explains inter-individual differences in disease susceptibility and severity.

Contribution of IL-12A and IL-12B Polymorphisms to Chlamydia trachomatis-Specific Cell-Mediated Immune Responses

Inherited variance in the IL‐12B gene is associated with susceptibility to Chlamydia trachomatis‐induced tubal factor infertility and disease severity. In this study, our aim was to discover how polymorphisms in IL‐12‐coding genes influence C. trachomatis‐induced immune responses and IL‐12 production. The study population consisted of 240 women. IL‐12A and IL‐12B single nucleotide polymorphisms (SNPs) were determined from isolated DNA using the Sequenom system with matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectrometry. We studied lymphocyte proliferative (LP) responses to C. trachomatis strains E and F elementary bodies (EBs) and recombinant chlamydial heat‐shock protein 60 (CHSP60) antigen. IL‐12p40 and IL‐12p70 levels were measured using the BD Flex Set method. We found a statistically significant association between the C. trachomatis EB antigen‐specific LP response and the rs2853694 SNP (P = 0.02). Our study demonstrates that the IL‐12 cytokine family is involved in C. trachomatis‐specific immune responses. Moreover, C. trachomatis‐induced IL‐12 production and the IL‐12B rs2853694 SNP partially explain individual variation in the C. trachomatis LP response.