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Transfer of humoral immunity from the mother to her off-spring
Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background. It has been established that T cell responses of foetal origin to inhalant allergens are present in most cord blood samples. These immune responses could possibly be explained by transplacental passage of peptides, either as free antigens or in complexes with IgG, providing the foetus with a trigger for the priming of the T cell system already in utero. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is unknown. IgA antibodies to inhalant allergens have not been previously detected in human milk.

Objective. The aim of this thesis was to explore whether inhaled allergens in serum and IgA antibodies in breast milk could contribute to the allergic immune responses to allergens in the children.

Methods. The presence of cat allergen Fel d 1 was analysed by ELISA in serum samples from cat allergic asthmatic children. To detect IgG immune complexes (IC), affmity chromatography purification and Western blotting were performed. Iri:nnune complexes with Fel d 1-IgE were detected by a modification of MagicLite, and their specificity was assessed by different approaches. Serum samples from allergic and non-allergic mothers, and cord blood from their infants, were measured for the presence of Fel d 1-IgG immune complexes by an amplified ELISA. Cord blood mononuclear cells (CBMC) of babies from allergic and non-allergic mothers were stimulated with cat allergen and the production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA and the levels related to the presence of IC. Furthermore, IgG1 and IgG4 antibodies to cat were measured by ELISA. Colostrum and samples of mature milk from allergic and non-allergic mothers were analysed for IgA antibodies to cat, P-lactoblobulin (BLG) and ovalbumin (OVA) by an amplified ELISA.

Results. The cat allergen Fel d I was detected in 70% of sera from cat allergic chilch'en, but not in any of the controls. The allergen was present in complexes with IgE and IgG antibodies as corroborated by different approaches. Immune complexes with IgG were detected in sera from allergic and non-allergic mothers, as well as in the cord blood from their babies, but neither the prevalence nor the levels of complexes were related to maternal allergy. This was also the case for IgG antibodies to cat. The production of IL-5, IL-10, IL-13 and IFN-γ by CBMC was not influenced by maternal atopy. Interferon-y secretion by CBMC after stimulation with cat allergen, however, was less conunonly detected in samples with immune complexes. Secretory IgA to cat and OVA allergens were frequently detected in colostrum and mature milk, while antibodies to BLG were less common. The antibody levels to cat and BLG were similar in allergic and non-allergic mothers.

Conclusion. The presence of IC with allergens may contribute to maintaining immune responsiveness and sensitivity in allergic individuals. Low levels of transplacentally transferred IC can conceivable provide the foetus with the signal for priming ofT cell responses to inhalant allergens. This seems to be a nonnal mechanism, as the immune responses are not related to maternal allergy. Low level exposure of the maternal mucosa, e.g. by inhalant allergens, can induce IgA antibody secretion in breast milk, but this mechanism is not related with any protective effect against allergy.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2001. , 111 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 692
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-28554Local ID: 13707ISBN: 91-7219-984-9 (print)OAI: oai:DiVA.org:liu-28554DiVA: diva2:249365
Public defence
2001-10-19, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-08-21Bibliographically approved
List of papers
1. Circulating cat allergen and immune complexes in cat- allergic children
Open this publication in new window or tab >>Circulating cat allergen and immune complexes in cat- allergic children
Show others...
1998 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 28, no 10, 1258-1263 p.Article in journal (Refereed) Published
Abstract [en]

Background

The first encounters with allergens seem to influence the development of allergy. Food antigens have been detected in sera as free antigens and in complexes with IgG but less is known about the presence of inhalant allergens.

Objective

To investigate the presence of the major cat allergen Fel d 1, either as free allergen and/or in complexes with IgG and IgE antibodies in sera from atopic children.

Methods

Serum samples from 33 cat allergic asthmatic children, 7–17 years old, and 15 non-allergic controls were investigated for the presence of Fel d 1 by ELISA (detection limit 0.13 μg/L). To detect immune complexes (IC), the IgG fraction from Fel d 1 positive sera was purified by affinity chromatography. Purified and non-absorbed material was then analysed for allergen content and specific IgG antibody levels. Immune complexes with Fel d 1 IgE were detected by coupling anti-Fel d 1 MoAb to paramagnetic particles.

Results

Fel d 1 was detected (0.15–1.8 μg/L) in 23 of the 33 patients (70%) but not from any of the controls. Eighteen samples contained IgE-Fel d 1 IC and two of four tested samples contained Fel d 1 in the IgG fraction. Electrophoresis and Western blotting of IgG purified material using anti-Fel d 1 MoAb corroborated the presence of IgG-Fel d 1 IC.

Conclusion

Free-circulating inhalant allergen and IC with allergens may contribute to maintaining immune responsiveness and sensitivity.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80093 (URN)10.1046/j.1365-2222.1998.00384.x (DOI)
Available from: 2012-08-20 Created: 2012-08-20 Last updated: 2017-12-07Bibliographically approved
2. Presence of Fel d 1 - IgE immune complexes in sera from cat allergic individuals
Open this publication in new window or tab >>Presence of Fel d 1 - IgE immune complexes in sera from cat allergic individuals
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: We have recently reported the presence of immune complexes (IC) with the inhalant allergen Fel d I, in serum samples from cat allergic children. It was not entirely excluded however that these findings were due to the presence of human antibodies against cat serum albumin. The objective of this work was to confirm the presence of the major cat allergen Fel d I in complexes with IgE and to assess the specificity of the human IgE antibodies to cat allergen.

Methods: Serum samples from 27 cat allergic children were investigated. For the detection of Fel d 1-IgE IC, a chemiluminescent immunoassay was modified by coupling an anti-Fel d I monoclonal antibody to paramagnetic particles. Levels of IgE antibodies to cat allergens were determined by chemiluminiscense and RAST, and IgG4 antibody levels by RAST.

Results: Fifteen samples contained IgE-Fel d I IC. The levels of IC correlated with the levels of specific lgE antibodies to cat allergen correlated (r=0.48; p<0.05). All the samples of the 27 cat allergic children contained IgE and IgG4 antibodies against cat allergen, while IgE and IgG4 antibodies to cat serum were only demonstrated in 4/27 (14 %) and 6/27 (22%) samples respectively. Conclusions: Immune complexes with the major cat allergen, Fel d I, were commonly present in serum samples from cat allergic children.

Keyword
Allergen, Fel d 1, cat serum albumin, IgE, IgG, IgG4, immune complex
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80113 (URN)
Available from: 2012-08-21 Created: 2012-08-21 Last updated: 2012-08-21Bibliographically approved
3. Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
Open this publication in new window or tab >>Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
2001 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 2, 59-64 p.Article in journal (Refereed) Published
Abstract [en]

It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25850 (URN)10.1034/j.1399-3038.2001.012002059.x (DOI)10287 (Local ID)10287 (Archive number)10287 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-21Bibliographically approved
4. Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
Open this publication in new window or tab >>Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
2001 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 12, no 2, 59-64 p.Article in journal (Refereed) Published
Abstract [en]

It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25850 (URN)10.1034/j.1399-3038.2001.012002059.x (DOI)10287 (Local ID)10287 (Archive number)10287 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-21Bibliographically approved
5. Cat allergen-induced cytokine secretion and Fel d 1–immunoglobulin G immune complexes in cord blood
Open this publication in new window or tab >>Cat allergen-induced cytokine secretion and Fel d 1–immunoglobulin G immune complexes in cord blood
2004 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 34, no 4, 591-596 p.Article in journal (Refereed) Published
Abstract [en]

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-γ, 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-γ by CBMC was not influenced by maternal atopy, but IFN-γ 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-γ seems to be related with the presence of IC in cord blood.

Keyword
allergen, cord blood, cytokine, Fel d 1, IgG, immune complex
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-22341 (URN)10.1111/j.1365-2222.2004.1924.x (DOI)1542 (Local ID)1542 (Archive number)1542 (OAI)
Note
On the day of the defence day the status of this article was submitted.Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-08-21Bibliographically approved

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