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Biomedical subjects

M C Jenmalm

Publications and source records attributed to M C Jenmalm.

At least 19 recordsLinked to original sources
PubMed2007

Decreased up-regulation of the interleukin-12Rbeta2-chain and interferon-gamma secretion and increased number of forkhead box P3-expressing cells in patients with a history of chronic Lyme borreliosis compared with asymptomatic Borrelia-exposed individuals.

Lyme borreliosis (LB) can, despite adequate antibiotic treatment, develop into a chronic condition with persisting symptoms such as musculoskeletal pain, subjective alteration of cognition and fatigue. The mechanism behind this is unclear, but it has been postulated that an aberrant immunological response might be the cause. In this study we investigated the expression of the T helper 1 (Th1) marker interleukin (IL)-12Rbeta2, the marker for T regulatory cells, forkhead box P3 (FoxP3) and the cytokine profile in patients with a history of chronic LB, subacute LB, previously Borrelia-exposed asymptomatic individuals and healthy controls. Fifty-four individuals (12 chronic LB, 14 subacute LB, 14 asymptomatic individuals and 14 healthy controls) were included in the study and provided a blood sample. Mononuclear cells were separated from the blood and stimulated with antigens. The IL-12Rbeta2 and FoxP3 mRNA expression was analysed with real-time reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of IL-12Rbeta2 on CD3(+), CD4(+), CD8(+) and CD56(+) cells was assessed by flow cytometry. Furthermore, the secretion of interferon (IFN)-gamma, IL-4, IL-5, IL-10, IL-12p70 and IL-13 was analysed by enzyme-linked immunospot (ELISPOT) and/or enzyme-linked immunosorbent assay (ELISA). Chronic LB patients displayed a lower expression of Borrelia-specific IL-12Rbeta2 on CD8(+) cells and also a lower number of Borrelia-specific IFN-gamma-secreting cells compared to asymptomatic individuals. Furthermore, chronic LB patients had higher amounts of Borrelia-specific FoxP3 mRNA than healthy controls. We speculate that this may indicate that a strong Th1 response is of importance for a positive outcome of a Borrelia infection. In addition, regulatory T cells might also play a role, by immunosuppression, in the development of chronic LB.

Adult↗
PubMed2006

Cytokine responses to allergens during the first 2 years of life in Estonian and Swedish children.

BACKGROUND: The prevalence of atopic disease among children in the formerly socialist countries in Europe, with a life style similar to that prevailing in Western Europe 30-40 years ago, is low, whereas there has been a pronounced increase in industrialized countries over the last decades. The environment during infancy influences the risk of developing allergy for many years, perhaps even for life. OBJECTIVE: To investigate the development of allergen-specific cytokine responses during the first 2 years of life in two geographically adjacent countries with marked differences in living conditions and incidence of atopic diseases, i.e. Estonia and Sweden. METHODS: The development of immune responses to food (beta-lactoglobulin (BLG) and ovalbumin (OVA)) and inhalant (cat and birch) allergens was studied from birth up to the age of 2 years in 30 Estonian and 76 Swedish infants. Clinical investigation and skin prick tests were performed and blood samples were obtained at birth and at 3, 6, 12 and 24 months. RESULTS: The levels of IL-5, IL-10 and IL-13 secreted by peripheral blood mononuclear cells stimulated with BLG, OVA and cat allergen in Estonian and Swedish infants declined during the first 3 months of life. All cytokines then progressively increased in the Swedish infants, indicating the replacement of non-specifically responding immature cord blood T cells with specific T memory cells, which are primed postnatally. The resurgence of allergen-specific responses in the Estonian infants was less marked. These differences were particularly notable for birch-specific T cell responses, which correlated with development of atopic disease in the Swedish children. CONCLUSIONS: The development of specific T cell memory to food and inhalant allergens during the first 2 years of life differs between infants living in Sweden and Estonia, and mirrors the disparate patterns of expression of allergic disease which subsequently develops in the respective populations.

Allergens↗
PubMed2005

Atopic sensitization and atopic dermatitis in Estonian and Swedish infants.

BACKGROUND: Early life events seem to have a major impact on the development of tolerance or sensitization. OBJECTIVE: The aim of the study was to compare the prevalence of sensitization and atopic dermatitis (AD) during the first 2 years of life in Estonia and in Sweden. METHODS: Two groups comprising 110 Estonian and 123 Swedish infants were followed from birth up to 2 years of age. Data about symptoms of allergy, infections and use of antibiotics were obtained by questionnaires. Clinical examinations, skin prick tests (SPTs) with food and inhalant allergens, and blood sampling for IgE analyses were carried out at 3, 6, 12 and 24 months. RESULTS: The cumulative incidence of AD and positive SPTs were lower in the Estonian than the Swedish infants (14% vs. 24%; P = 0.06 and 13% vs. 24%; P = 0.03), while circulating IgE antibodies were more common (39% vs. 27%; P = 0.06) and often present without any clinical significance in Estonian children. Estonian infants had respiratory illnesses more often and they had received antibiotics more frequently. Use of antibiotics increased the risk for positive SPT in the Estonian (odds ratio = 1.7, 95% confidence interval = 1.1-2.5), but not in the Swedish infants. This may be explained by the use of broad-spectrum antibiotics in Estonia, while in Sweden mostly penicillin was prescribed. CONCLUSIONS: The prevalence of AD and positive SPTs was lower in the Estonian than the Swedish infants, while circulating IgE antibodies were more common and often present without any clinical significance. These differences cannot simply be explained by infections, or use of broad-spectrum antibiotics in the two countries, although more the natural lifestyle in Estonia may be contributing factor.

Antibodies, Anti-Idiotypic↗
PubMed2004

Effect of cryopreservation on expression of Th1 and Th2 cytokines in blood mononuclear cells from patients with different cytokine profiles, analysed with three common assays: an overall decrease of interleukin-4.

Studies on cytokine expression in blood cells are commonly performed on cryopreserved cells. Previous studies show that cryopreservation affects cytokine expression, but the findings are not consistent. This may be due to divergent effects of freezing on different cytokines, different stimuli, and different patient groups or to the use of different assays in the studies. This study was designed to investigate the effect of freezing on spontaneous, auto-antigen, allergen, and mitogen induced cytokine secretion from peripheral blood mononuclear cells from several groups of patients expressing different cytokine profiles; multiple sclerosis, atopic children, non-atopic children, and pregnant women. The expression of IFN-gamma, IL-4, IL-5, IL-9, IL-10, and IL-13 was analysed with ELISA, ELISPOT and/or real time RT-PCR. Our data provide evidence that the process of cryopreservation and thawing does affect the expression of cytokines, both at the protein and the mRNA level. Moreover, the effect varied among different cytokines, different stimuli, and different patient groups, which partly may be explained by differences in optimal freezing conditions for non-activated and activated cells. An increase of allergen and PHA stimulated IFN-gamma secretion in atopic children was found following cryopreservation, but no such increase in auto-antigen induced IFN-gamma was seen in MS-patients. The most consistent finding was that expression of IL-4 was generally decreased in spontaneous and auto-antigen/allergen induced expression in cryopreserved cells. In conclusion, this study points out the importance of investigation of the effects of freezing for each cytokine, stimuli and patient group before using frozen cells in studies of in vitro cytokine secretion.

Adult↗
PubMed2004

Reduced levels of soluble CD14 in atopic children.

BACKGROUND: A reduced microbial stimulation has been reported as a reason for the increasing prevalence of atopic diseases in industrialized countries. Antigen-presenting cells (APC), responding to microbial signals by pattern recognition receptors such as CD14, have an important role in the development of the Th1/Th2 balance. OBJECTIVE: We hypothesized that atopic children have a lower expression of CD14 on monocytes and lower soluble CD14 levels (sCD14). METHODS: Seventy-six children were followed prospectively from birth and signs of atopic disease were evaluated. The expression of CD14 on monocytes was analysed with flow cytometry at 0, 3, 6, 12 and 18 months. Circulating levels of sCD14 were analysed by ELISA and total IgE was analysed by fluoroenzymo immunoassay at these ages, and in a subgroup, followed up at 7 years. RESULTS: Levels of sCD14 were reduced at 7 years both in children with a current or a cumulative history of atopy compared to non-atopic children with P=0.002 and 0.001, respectively. Sensitized children with atopic symptoms had lower sCD14 at 3 and 18 months and at 7 years of age than non-atopic non-sensitized children with P=0.023, 0.039 and 0.008, respectively. CONCLUSION: The lower levels of sCD14 observed in atopic children may be a consequence of an atopic family heredity and/or atopic disease, but it may also reflect a reduced capacity to respond to microbial signals.

Aging↗
PubMed2004

Cat allergen-induced cytokine secretion and Fel d 1-immunoglobulin G immune complexes in cord blood.

BACKGROUND: We have recently obtained evidence for the presence of immune complexes (IC) in cord blood from allergic and non-allergic mothers. Such complexes could conceivably provide the fetus with the initial trigger for the priming of the T cell system already in utero. OBJECTIVE: To relate the presence of Fel d 1-IgG IC to T cell cytokine production in cord blood mononuclear cells (CBMCs) after stimulation with cat allergen. METHODS: CBMC obtained from babies of 15 allergic and 22 non-allergic mothers were cultured in the presence of cat allergen. The production of IFN-gamma, IL-5, IL-10 and IL-13 was determined by ELISA. Furthermore, IgG1 and IgG4 antibodies to cat allergen in cord blood samples were measured by ELISA. A more sensitive ELISA was used to measure Fel d 1-IgG IC. RESULTS: The prevalence and levels of IC were similar in cord blood from children of allergic and non-allergic mothers. The production of IL-5, IL-10. IL-13 and IFN-gamma by CBMC was not influenced by maternal atopy, but IFN-gamma was less commonly detected in samples with IC. There was no association between the presence of IC and any other cytokines. The levels of IgG1 and IgG4 antibodies were similar in both groups, and tended to be associated with the presence of IC. CONCLUSION: Immune complexes in cord blood may represent a normal mechanism for inducing primary immune responses, as the responses in babies from allergic and non-allergic mothers were largely similar. Low levels of IFN-gamma seems to be related with the presence of IC in cord blood.

Allergens↗
PubMed2003

Endotoxin levels in Estonian and Swedish house dust and atopy in infancy.

BACKGROUND: Immune responses, including those to allergens, may be T helper (Th)2 skewed in newborns. In order to redress the fetal Th1/Th2 imbalance, Th1-stimulating factors, such as bacterial endotoxin, may be required. The increasing prevalence and severity of atopic diseases in industrialized countries, which are in marked contrast with the low prevalence of allergy among children in the formerly socialist countries of Europe, have been suggested to be caused by a reduced microbial stimulation. AIM: To relate the endotoxin levels in house dust from two countries with a low (Estonia) and a high (Sweden) prevalence of allergy to the development of atopic disease and sensitization in the children during the first 2 years of life. METHODS: The study included 108 children from Tartu, Estonia and 111 children from Linköping, Sweden. Skin prick tests were performed at 3, 6, 12 and 24 months of age, and questionnaires were distributed to the families. At 24 months, a paediatrician examined the children. Dust samples were collected from mattresses and carpets and the endotoxin concentration was determined by a chromogenic Limulus assay. RESULTS: The endotoxin levels were higher in Estonian than in Swedish house dust (median levels 29 (range 0.25-280) and 14 (range 0.25-99) EU/mg dust, respectively, P < 0.001). Furthermore, the levels were inversely related to the development of atopic disease and sensitization in the Swedish, but not in the Estonian, children. CONCLUSIONS: The low prevalence of atopic disease in Estonia may, at least in part, be related to the high endotoxin levels in this country. The findings support that high levels of endotoxin, or other bacterial products with Th1-stimulating properties, might protect children from developing atopic disease.

Beds↗
PubMed2002

Immune responses to birch in young children during their first 7 years of life.

BACKGROUND: The character of immune responses to allergens during the first years of life may decide whether the individual will become tolerant or develop allergy later in life. OBJECTIVE: To study the development of immune responses to the seasonal inhalant allergen birch over the first 7 years of life. METHODS: Blood samples were obtained from 21 children who were followed prospectively from the second to the seventh pollen season of life. Birch-induced cytokine production and IgG subclass antibodies to rBet v 1 were analysed with ELISA, mRNA expression with real time PCR, IgE antibodies to birch with Magic Lite and birch-induced mononuclear cell proliferation with 3H-thymidine incorporation. RESULTS: Birch-induced IFN-gamma and IL-10 production increased with age, both in atopic and non-atopic children, while birch-induced IL-13 production decreased. The two children who were sensitized and developed clinical allergy to birch showed persistent IL-4 and IL-5 production and IL-9 mRNA expression, as well as Th2-associated IgG4 responses. Transient Th2-like responses were observed among the other children. Proliferative responses and IgG1 antibodies were seen in all children. CONCLUSIONS: Immune responses to birch can be demonstrated in all children, during the first 7 years of life, regardless of atopic status. A transient early Th2-like response is down-regulated after the fourth pollen season, except in children who develop clinical allergy to the particular allergen.

Aging↗
PubMed2002

Total and allergen-specific immunoglobulin A levels in saliva in relation to the development of allergy in infants up to 2 years of age.

BACKGROUND: The association between salivary IgA levels and development of allergy is controversial and the employed methodology has been questioned. OBJECTIVE: The aim of the study was to relate the levels of total IgA, SIgA and allergen-specific IgA antibodies in saliva to the development of allergy in infants during the first 2 years of life. METHODS: Saliva samples from 80 infants participating in a prospective study regarding the development of allergy were collected at 3 or 6, and 12 and 24 months of age. Total IgA, SIgA and Fel d 1 and beta-lactoglobulin specific IgA levels were analysed with ELISA. RESULTS: The levels of total IgA and SIgA increased with age. The number of samples with detectable IgA to Fel d 1 tended to increase with age, whereas the opposite was observed for IgA to beta-lactoglobulin. Infants who developed allergy tended to have higher levels of total IgA, and allergen-specific IgA was more commonly detected than in non-allergic children. In contrast, non-allergic children tended to have higher levels of SIgA. Furthermore, the levels of SIgA were higher in sensitized infants with no allergic symptoms than in sensitized children with symptoms. Infants with allergic parents had lower SIgA levels than infants without. Direct exposure to cat and cow's milk did not influence the levels of allergen-specific IgA levels, nor was there any association between breast-feeding and IgA production. CONCLUSION: The kinetics of food and inhalant allergen-specific IgA in saliva during the first 2 years of life is similar to what has earlier been shown for IgG in serum. Development of allergy tended to be associated with high levels of total and allergen-specific IgA antibodies, but low levels of SIgA. Furthermore, high levels of SIgA seemed to protect sensitized children from developing allergic symptoms during the first 2 years of life, supporting a possible protective role of SIgA against development of allergy.

Allergens↗
PubMed2001

Allergen-induced Th1 and Th2 cytokine secretion in relation to specific allergen sensitization and atopic symptoms in children.

BACKGROUND: Allergic diseases are believed to be due to T helper (Th)2-like immunity to allergens in affected tissues, and immune responses to allergens are characterized by a cross-regulation between Th1 and Th2 cells. Atopic individuals may develop IgE antibodies to only one or more allergens. However, the mechanisms behind sensitization to a specific allergen, e.g. why an individual develops IgE to cat but not birch, are not known. Our aim was to study birch- and cat-induced Th1 and Th2 cytokine secretion in children who were sensitized to birch but not to cat, and vice versa. MATERIALS AND METHODS: The subjects in the study were 60 12-year-old children. Seventeen of the children were sensitized (skin prick test and circulating IgE positive) to birch but not cat, 13 were sensitized to cat but not birch, 11 were sensitized both to birch and cat, and 19 children were skin prick test and circulating IgE negative. Forty-six children had a history of atopic symptoms, and 42 of them had current symptoms. Peripheral blood mononuclear cells were separated from venous blood and stimulated with cat or birch allergen. The levels of IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-gamma in the cell supernatants were analysed by ELISA. RESULTS: Sensitized children produced more of the Th2 cytokines IL-4, IL-5, IL-9 and IL-13 than non-sensitized atopic and non-atopic children in response to stimulation with the allergen they were sensitized to. High levels of the Th2 cytokines IL-4 and IL-5 and low levels of the anti-inflammatory cytokine IL-10 were associated with atopic symptoms, and high cat-induced IL-9 levels with asthma. CONCLUSIONS: The Th2 cytokines IL-4, IL-5, IL-9 and IL-13 were all commonly detected in sensitized children after stimulation with the specific, in contrast to an unrelated, allergen. Atopic symptoms were associated with increased levels of IL-4 and IL-5 and tended to be associated with low levels of IL-10, and asthma with high cat-induced IL-9 levels.

Allergens↗
PubMed2001

PHA-induced IL-12R beta(2) mRNA expression in atopic and non-atopic children.

BACKGROUND: IL-12 is a strong inducer of Th1 responses. Stimulation via the CD2 receptor increases IFN-gamma production and enhances the responsiveness of activated T-cells to IL-12, possibly due to an up-regulation of the signal transducing beta(2) chain of the IL-12 receptor (IL-12R beta(2)). Atopic children have a reduced Th1-like immunity and a reduced CD2 expression. Our hypothesis is that atopic individuals have a reduced function of the CD2 pathway, causing reduced responsiveness to IL-12 and decreased IFN-gamma production. OBJECTIVE: The aim was to study the mRNA expression of the IL-12R beta(2) chain, after stimulation via the CD2 pathway in peripheral blood mononuclear cells (PBMC), of atopic and non-atopic children, and to investigate correlations to the production of Th1 and Th2 cytokines. MATERIALS AND METHODS: The study included 23 skin prick test positive, and 9 non-sensitized, 12-year-old children. PBMC were stimulated for 24 h with phytohemagglutinin (PHA) (2 microg/mL), which stimulates T cells through the CD2 pathway. Expression of IL-12R beta(2) mRNA was analysed by quantitative real time PCR and the cytokine production was detected with ELISA. RESULTS: Atopic and non-atopic children had similar baseline expression of IL-12R beta(2) mRNA, whereas PHA-induced IL-12R beta(2) mRNA expression was lower in atopic than in non-atopic children. The PHA-induced IL-12R beta(2) mRNA expression correlated well with the PHA-induced IFN-gamma production and with the IFN-gamma/IL-4 ratio. CONCLUSION: PBMC from atopic children expressed less IL-12R beta(2) mRNA than non-atopic children after stimulation via the CD2 pathway (PHA). This may indicate a reduced capacity to respond to Th1-inducing stimuli in atopic children.

Child↗
PubMed2000

Expression of and responses to CD2 and CD3 in 18-month-old children with and without atopic dermatitis.

We hypothesize that atopy is associated with a reduced T-cell function early in life and an imbalance in cytokine production. The purpose of this study was to investigate the expression of and responses to CD2 and CD3 in children who did or did not develop atopic dermatitis early in life. The expression of CD2 and CD3 was analyzed by flow cytometry, and proliferation of CD2 and CD3 was studied by 3H-thymidine incorporation in phytohaemagglutinin (PHA)- and anti-CD3-stimulated peripheral blood mononuclear cells (PBMC) of 18-month-old children, 25 with and 29 without atopic dermatitis. Exogenous interleukin (IL)-2 was added to compensate for possible functional differences in accessory cells. Anti-CD3-induced secretion of IL-4, IL-5, IL-6, IL-10, IL-13, and interferon-gamma (IFN-gamma) was analyzed by enzyme-linked immunosorbent assay (ELISA). Atopy was associated with a low proportion of CD2+ lymphocytes. Responsiveness to PHA, which activates lymphocytes partly via the sheep erythrocyte receptor, CD2, was reduced in the allergic children. The anti-CD3-induced proliferation declined more rapidly with antibody dilution in the allergic than in the non-allergic children. Atopic dermatitis was associated with high levels of anti-CD3-stimulated IL-5 secretion. The IL-4/IL-10 and IL-4/ITFN-gamma ratios were higher in children with elevated total immunoglobulin E (IgE) levels. Skin prick test-negative children with eczema produced higher levels of IL-10 than skin prick test-positive children. In conclusion, atopic children have a reduced T-cell function. Atopic dermatitis is associated with increased IL-5 production, while high total IgE levels are associated with high IL-4/IFN-gamma and IL-4/IL-10 ratios.

CD2 Antigens↗
PubMed2000

Cord blood levels of immunoglobulin G subclass antibodies to food and inhalant allergens in relation to maternal atopy and the development of atopic disease during the first 8 years of life.

BACKGROUND: Factors that either protect from or enhance the development of atopic disease appear to be acting early in life. The gestational environment, including maternal immune responses, such as transplacentally transferred immunoglobulin (Ig) G antibodies to allergens, may be of importance in this respect, since allergen-specific immunity has been demonstrated to develop in utero. OBJECTIVE: To evaluate the relation between cord blood IgG subclass antibodies to allergens, maternal atopy and development of atopic disease in the children. MATERIAL AND METHODS: The study group comprised a cohort of 96 children participating in a prospective study up to 8 years of age. Cord blood IgG subclass antibodies to ovalbumin, beta-lactoglobulin, Bet v 1 and cat dander were analysed by ELISA. RESULTS: The levels of all IgG subclass antibodies to ovalbumin and rBet v 1 were higher in newborn infants with an atopic mother, as compared with babies with nonatopic mothers. IgG1 antibody levels to cat and IgG4 antibody levels to beta-lactoglobulin and cat were also higher in atopic than in nonatopic mothers, whereas the other subclass antibody levels to those allergens were similar. High levels of cord blood IgG antibodies to cat and birch, but not to the food allergens, were associated with less atopic symptoms in the children during the first 8 years of life. Moreover, children who developed IgE antibodies to cat had lower levels of IgG antibodies to that allergen at birth. CONCLUSIONS: High levels of cord blood IgG subclass, especially IgG4, antibodies to food and inhalant allergens are associated with maternal atopy. High levels of IgG antibodies to inhalant, but not food, allergens are associated with less development of atopy in the children.

Administration, Inhalation↗
PubMed2000

Cytokines in breast milk from allergic and nonallergic mothers.

The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. The aim of this study was to investigate the concentrations of cytokines involved in allergic reactions and IgA antibody production in breast milk from allergic and nonallergic mothers. The cytokine concentrations were determined in colostrum and 1-mo. milk samples from 24 mothers with, and 25 mothers without, atopic symptoms, using commercial ELISA kits. The immunosuppressive cytokine transforming growth factor-beta was predominant and was detectable in all milk samples. IL-6 was detected in the majority of colostral and mature milk samples, whereas the other cytokines were less commonly detected. The concentrations of IL-6, IL-10, and transforming growth factor-beta, which are all involved in IgA synthesis, correlated with each other and with total IgA concentrations in colostrum. The concentrations of IL-4 were higher in colostrum from allergic than nonallergic mothers, and similar trends were seen for IL-5 and IL-13. In conclusion, transforming growth factor-beta and IL-6 were the predominant cytokines in human milk. The correlation between the concentrations of cytokines involved in IgA synthesis, i.e. IL-10, IL-6, and transforming growth factor-beta, may explain the stimulatory effect on IgA production in breast-fed babies. Varying concentrations of IL-4, IL-5, and IL-13 may explain some of the controversy regarding the possible allergy-preventive effect of breast-feeding.

Case-Control Studies↗
PubMed2000

Chemoattractant factors in breast milk from allergic and nonallergic mothers.

The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. Recently, we showed that allergic mothers had higher concentrations of IL-4 and lower concentrations of ovalbumin-specific IgA in their breast milk than nonallergic mothers. The aim of this study was to investigate the concentrations of chemokines and cytokines that are chemotactic to cells involved in allergic reactions in breast milk from allergic and nonallergic mothers. Cytokine and chemokine concentrations were determined with ELISA in colostrum and mature milk samples from 23 mothers with and 25 mothers without atopic symptoms. IL-8 was detected in all milk samples. RANTES (regulated on activation, normal T cell expressed and secreted), eotaxin, and IL-16 were detected in 50%, 76%, and 48%, respectively, in colostrum and less commonly in mature milk. Macrophage inflammatory protein-1alpha, however, could not be detected in any of the samples. The concentrations of IL-8 and RANTES were higher in breast milk from allergic, compared with nonallergic, mothers. In conclusion, the presence of chemoattractant factors in breast milk may be responsible for the traffic of leukocytes from the maternal circulation to the breast milk. The higher concentrations of RANTES and IL-8 in allergic mothers may partly explain the controversy regarding the protective effect of breast-feeding against the development of allergy by stronger chemotaxis and activation of cells involved in allergic diseases, and possibly by elevated IgE production.

Chemokine CCL11↗
PubMed1999

Development of immunoglobulin G subclass antibodies to ovalbumin, birch and cat during the first eight years of life in atopic and non-atopic children.

Immune responses to allergens in young children include both Th1- and Th2-like immunity, which may regulate the secretion of immunoglobulin (Ig) G subclass antibodies differently. The time, route and level of exposure to an allergen may be decisive with regard to whether sensitization or tolerance will ensue. To study this, we investigated the development of IgG subclass antibodies to food and inhalant allergens during childhood. The study group comprised a cohort of 96 children participating in a prospective study. IgG subclass antibodies to ovalbumin, Bet v 1 and cat dander were analyzed at birth, 6 and 18 months and 8 years by ELISA. IgG1 and IgG3 subclass antibodies to ovalbumin peaked at 18 months and then declined up to 8 years of age, whereas antibodies to the inhalant perennial allergen cat, but not the inhalant seasonal allergen birch, increased with age. Exposure to cat and birch tended to be associated with high antibody levels to those allergens, whereas antibody levels to ovalbumin were not related to exposure to egg. The presence of positive skin prick tests and circulating IgE antibodies correlated with high levels of IgG subclass antibody responses to the allergens. Atopic symptoms were associated with high levels of IgG subclass, particularly IgG4, antibodies to the allergens. The difference in antibody levels between atopic and non-atopic children was most marked at 6 months for ovalbumin. For the seasonal inhalant allergen birch, the difference was apparent from 18 months, whereas a difference in antibody levels to the perennial inhalant allergen cat was already present at 6 months. In conclusion, IgG subclass antibodies to food allergens peak in early infancy and are then down-regulated, whereas antibodies to the inhalant perennial allergen cat, but not the inhalant seasonal allergen birch, increase with age. Atopy is associated with high levels of IgG subclass, particularly IgG4, antibodies to allergens, supporting a deviation of the immune system towards Th2-like responses in atopic children.

Allergens↗
PubMed1999

Allergen-induced cytokine secretion in relation to atopic symptoms and immunoglobulin E and immunoglobulin G subclass antibody responses.

There are few studies on allergen-induced cytokine production in allergic children, and little is known of antigen-specific cytokine regulation of human immunoglobulin (Ig) G subclass antibody responses. An association with T-helper 1 (Th1)-like immunity and complement-activating antibodies remains to be demonstrated in humans. We have previously observed that atopic symptoms are associated with high levels of IgG subclass, especially IgG4, antibodies to birch and beta-lactoglobulin. The differences were seen early in life for the food allergen and increased with age for the inhaled allergen. The aim of this study was to investigate the association between atopic symptoms, birch allergen-, and beta-lactoglobulin-induced cytokine production in peripheral blood mononuclear cells (PBMC), and serum IgE and IgG subclass antibody responses to these allergens in children in order to further clarify the role of Th1- and Th2-like immunity in responses to various antigens. PBMC from 55 eight-year old children, who had been followed prospectively from birth, were stimulated with birch- and beta-lactoglobulin. Production of interleukin (IL)-5, IL-6, IL-10, IL-13 and interferon (IFN)-gamma was analysed by ELISA and expression of IL-4 and IL-9 mRNA by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). IgG subclass antibody levels to birch- and beta-lactoglobulin in serum were determined by ELISA, and IgE antibodies by Magic-Lite and CAP-RAST, respectively. Birch-induced expression of IL-4, but not of the other cytokines, was associated with IgE antibodies to birch. Furthermore, the IL-4 expression and IL-6 production correlated with serum IgG4 antibody levels to this allergen, and IFN-gamma secretion with IgG1 antibody responses. There were no correlations between beta-lactoglobulin-stimulated cytokine production and IgG subclass antibody levels to that allergen, except for a negative association between beta-lactoglobulin-stimulated IL-4 expression and IgG1 antibodies. Atopic children tended to have high levels of birch and beta-lactoglobulin-induced IL-5, IL-6 and IL-10 secretion. Birch-induced IL-4 expression may be the major factor in determining IgE antibody formation to that allergen, while allergen-induced IL-5, IL-6 and IL-10 secretion in PBMC is associated with atopic symptoms. Th1-like immunity to inhaled allergens could be associated with production of the opsonizing and complement-activating IgG1 antibody subclass, and Th2-like immunity with IgG4 antibody responses.

Allergens↗