Childhood cat exposure-related tolerance is associated with IL1A and IL10 polymorphisms.
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Animals↗
Biomedical subjects
Janne Hulkkonen
Publications and source records attributed to Janne Hulkkonen.
Mitogen induced activation, proliferation and surface antigen expression patterns in unmutated and hypermutated chronic lymphocytic leukemia cells.
OBJECTIVES: To determine whether the immunoglobulin V(H) gene mutational status has an effect on the activation, proliferation and surface antigen expression of chronic lymphocytic leukemia (CLL) cells when stimulated in vitro. METHODS: The proliferation and activation responses of CLL cells were studied in 22-immunoglobulin gene V(H) unmutated (UM-CLL) and 12 hypermutated (M-CLL) CLL cases in 4-day cultures. As the mitogen responses have been previously shown to be diverse in CLL, a case-specific strategy based on optimized mitogen combinations (OMCs) of interleukin-2 (IL-2), 12-O-tetradecanoylphorbol 13-acetate (TPA), Staphylococcus aureus Cowan 1 (SAC), and human recombinant tumor necrosis factor alpha (TNF) was applied in cell stimulation. The expression of 23 surface membrane antigens (CD5, CD11c, CD19, CD20, CD21, CD22, CD23, CD25, CD27, CD38, CD40, CD45, CD45RA, CD45RO, CD79b, CD80, CD95, CD124, CD126, CD130, FMC7, IgD, and IgM) was studied by flow cytometry at days 0 and 4. RESULTS: The proliferation and activation responses were similar in UM-CLL and M-CLL when OMCs contained IL-2, TPA or TNF. SAC induced faster proliferation in UM-CLL than in M-CLL. OMC stimulation induced preferential down-regulation of growth- promoting cell surface receptors CD5, CD21, and CD124 and preferential up-regulation of growth-inhibiting antigen CD80 in M-CLL. CONCLUSIONS: Difference in immunophenotypic evolution of UM-CLL and M-CLL can be demonstrated if appropriate matrix signals are provided. The pathways for CD5, CD21, CD124 (IL4R), and CD80 (B7-1) regulation should be further explored in relation with somatic hypermutation and outcome of CLL.
Antigens, CD↗
The effect of mannan-binding lectin variant alleles on coronary artery reactivity in healthy young men.
Mannan-binding lectin (MBL) is a serum acute-phase protein and a complement component secreted by the liver. Its deficiency caused by point mutations in the MBL gene has recently been associated with severe atherosclerosis. In this study, we investigated the effect of MBL variant alleles on coronary artery reactivity, which is an early marker of coronary dysfunction and predicts the development of atherosclerosis and coronary artery disease. The study population consisted of 51 apparently healthy, normo- or mildly hypercholesterolemic young men. Myocardial blood flow was measured at baseline and during adenosine-induced hyperemia with positron emission tomography (PET), and MBL genotyping was performed using restriction fragment-length polymorphism. As a result, MBL variant alleles had no effect on coronary artery reactivity. This finding suggests that MBL deficiency is not an independent risk factor for coronary dysfunction and early atherogenic changes but rather a co-factor in the development of atherosclerosis. Thus, the connection of MBL variant alleles with environmental risk factors in atherosclerosis should further be assessed.
Adult↗
Allergic rhinitis and polymorphisms of the interleukin 1 gene complex.
BACKGROUND: Allergic rhinitis is a chronic inflammatory disease with a genetic background. Inflammatory reactions are regulated by cytokines. Cytokine genes are polymorphic and have been implicated as candidate genes in allergy. OBJECTIVES: To study the significance of the interleukin 1 (IL-1) gene complex in allergic rhinitis. METHODS: Population-based, cross-sectional study. We studied the polymorphisms of 3 IL-1 gene complex genes, IL1A (+4845G>T), IL1B (-511 degrees C>T), and IL1RN (variable number of tandem repeats; IVS2, 86 bp, duplicates 2 to 5), in patients with allergic rhinitis. The study group consisted of 405 nonasthmatic individuals of whom 56 had allergic rhinitis. RESULTS: The genotype distribution differed significantly in all cytokine genes studied between subjects with and without allergic rhinitis. The difference was mainly due to an increased number of IL1A allele G homozygotes (67.9% vs 43.2%; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.5-5.1), IL1B heterozygotes (72.2% vs 47.4%; OR, 2.8; 95% CI, 1.5-5.3), and IL1RN allele 2 homozygotes (18.5% vs 7.5%; OR, 2.8; 95% CI, 1.3-6.2) in allergic rhinitis. Haplotype analysis revealed a significant difference in the distribution of IL-1 gene complex haplotypes between subjects with and without allergic rhinitis (P = 0.005, 10 df). CONCLUSIONS: The IL-1 gene complex polymorphism is strongly associated with allergic rhinitis in nonasthmatic individuals.
Adult↗
Surface antigen expression and correlation with variable heavy-chain gene mutation status in chronic lymphocytic leukemia.
Recent studies have demonstrated that B-cell chronic lymphocytic leukemia (CLL) consists of two clinical entities with either somatically hypermutated (M-CLL) or unmutated (UM-CLL) immunoglobulin variable heavy-chain (VH) regions. In view of the fact that the cellular biology of these two subsets of disease is currently unexplored, we performed an extensive analysis of the surface antigen expression and correlated this with the VH gene mutation status in a cohort of 32 CLL patients. Using polymerase chain reaction amplification and nucleotide sequencing, the VH genes were shown to be mutated in 10 cases (31%) and unmutated in 22 (69%). The expression of 27 surface membrane antigens in peripheral blood leukemic cells was analyzed by flow cytometry, measuring both the percentage of positive cells as well as the geometric mean fluorescence intensity (GMF). Most of the surface membrane antigens (CD5, CD11c, CD19, CD20, CD21, CD22, CD23, CD25, CD40, CD45, VD79b, CD80, CD95, CD122, CD124, CD126, CD130, CD154, IgM, and IgD) showed a similar expression pattern in both UM-CLL and M-CLL patients. The similarity of M-CLL and UM-CLL, as demonstrated here for the first time with many protein markers, indicates a considerably homogeneous phenotype in both subsets. Furthermore, CD27 was strongly expressed in all cases, which may suggest a memory cell phenotype for both M-CLL and UM-CLL. More positive cells in the UM-CLL group were observed regarding CD38, but CD38 was not a good predictor of VH gene mutation status. Seventy percent of the M-CLL cases, but only 36% of UM-CLL cases, were Ig-lambda+. The most striking differential expression, however, was observed in the two slicing variants of the common leukocyte antigen CD45, namely CD45RO and CD45RA. CD45RO expression was significantly associated with M-CLL, whereas the GMF intensity of CD45RA tended to be associated with UM-CLL. The role of these CD45 splicing variants in the pathogenesis of CLL deserves further investigation.
Antigens, Surface↗
CD80 antigen expression as a predictor of ex vivo chemosensitivity in chronic lymphocytic leukemia.
We investigated the correlation between expression of 31 surface membrane antigens and chemosensitivity of peripheral blood mononuclear cells from 36 patients with CLL. The sensitivity of CLL cells to nine drugs (2'-chlorodeoxyadenosine, cisplatin, chlorambucil, cyclosporin A, doxorubicin, fludarabine, prednisolone, verapamil and vincristine) and two types of irradiation (gamma and UV-irradiation) was determined from dose-response curves of 4-day cultures ex vivo. The results indicated that the CLL cases responding to purine analogs (2'-chlorodeoxyadenosine and fludarabine) can be identified according to CD80 expression: all resistant cases had low or negative CD80 expression. No other correlations were revealed. CD80 may be a surrogate chemosensitivity marker for purine analogs.
Antineoplastic Agents↗
The IL1A genotype associates with atopy in nonasthmatic adults.
BACKGROUND: The skin prick test is used to examine specific IgE-mediated allergic responses. Generally, results accord well with anamnestic information on atopy. Several genetic factors probably affect the strength of allergen-mediated skin test reactions. OBJECTIVE: We sought to investigate skin test findings in a population-based sample of adult asthmatic patients and control subjects and to establish whether the IL1A genotype affects allergy testing. METHODS: We analyzed the single G-to-T base exchange polymorphism in exon 5 at +4845 of the gene encoding IL-1alpha (IL1A) in adult asthmatic patients (n = 245) and nonasthmatic control subjects (n = 405). The data were assessed for correlation with data on the skin test responses of these subjects to 22 common allergens. RESULTS: The IL1A genotype distribution and allele frequencies proved similar in patients and control subjects. Surprisingly, the IL1A genotype distribution was markedly different in control subjects with positive (ie, >/=1 positive reaction) and negative skin test responses (P =.006). This difference was caused by an increase in the frequency of the rarer allele 2 in control subjects with negative skin test responses (P =.004). CONCLUSION: Our study demonstrates that the IL1 gene complex is involved in the regulation of IgE-mediated atopic reactions. The results suggest that skin test responses to specific allergens are differently regulated in nonasthmatic and asthmatic subjects. Because of the potential role of the IL1A genotype as a confounding factor in skin prick testing, these results require special attention and should be further evaluated in other clinical settings.
Adult↗
The balance of inhibitory and excitatory cytokines is differently regulated in vivo and in vitro among therapy resistant epilepsy patients.
PURPOSE: Excessive neuronal activity and seizures directly stimulate cytokine expression. In this study we investigated cytokine production in circulating blood and peripheral blood mononuclear cells (PBMC) in order to assess the cellular origin of these cytokines in patients with therapy resistant epilepsy. METHODS: We compared the levels of plasma IL-1beta, IL-1Ra and IL-6 in 10 patients with therapy resistant localization-related epilepsy and in healthy volunteers. The spontaneous and exogenously stimulated production of these cytokines was studied in PBMC cultures using EIA. Moreover, cell-specific cytokine production was studied using flow cytometry. RESULTS: Highly pro-inflammatory cytokine profile (high IL-6, low IL-1Ra and low IL-1Ra/IL-1beta ratio) was observed in plasma from patients with epilepsy. Spontaneous and LPS stimulated cytokine release was similar in PBMC cultures of patients and control subjects. When cells were stimulated with OKT3 the cytokine response profiles in patients with epilepsy were almost opposite (anti-inflammatory) to the profile which was observed in circulating blood. Low IL-6 was observed in cell cultures of patients when stimulated with PDBu + A23187. Flow cytometric analysis revealed that the percentages of IL-1beta, IL-1Ra and IL-6 positive monocytes were similar in patients and control subjects. CONCLUSIONS: Patients with therapy resistant epilepsy display a pro-inflammatory profile of plasma cytokines without any evidence of increased production from PBMC. These results suggest that the most likely origin for these cytokines is the brain, where cytokines can exert neuromodulatory functions.
Adolescent↗