The INDIVIDUALIST

A Wiki about biochemical individuality

Difference (from prior minor revision)

Added: 20a21,22

> ====Abstracts====
> <include "Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes.">


Serology

See also

Description

Immunoglobulin E (IgE) is an antibody subclass (known as "isotypes"), found only in mammals. Although IgE is typically the least abundant isotype - blood serum IgE levels in a normal ("non-atopic") individual are ~150ng/ml, compared to 10mg/ml for the IgGs (the isotypes responsible for most of the classical adaptive immune response) - it is capable of triggering the most powerful immune reactions. Most of our knowledge of IgE has come from research into the mechanism of a form of allergy known as Type 1 hypersensitivity.

http://www.dadamo.com/wiki/ige.jpg

Physiology

IgE's role in allergy is presumably inappropriate — why would a systemic anaphylactic reaction to a harmless substance be biologically useful? There is much speculation into what positive aspects IgE has, and so far, circumstantial evidence in animal models and statistical population trends have hinted that IgE may be beneficial in fighting gut parasites such as Schistosoma mansoni, but this has not been conclusively proven in humans.

Although it is not yet well understood, IgE may play an important role in the immune system’s recognition of cancer (1), in which the stimulation of a strong cytotoxic response against cells displaying only small amounts of early cancer markers would be beneficial. Of course, if this were the case, anti-IgE treatments such as Omalizumab might have some unforeseen side effects.

Role in disease

Atopic individuals (people who suffer from true IgE-mediated allergies) can have up to 10 times the normal level of IgE in their blood (as do sufferers of hyper-IgE syndrome). However, this may not be a requirement for symptoms to occur as has been seen in asthmatics with normal IgE levels in their blood - recent research has shown that IgE production can occur locally in the nasal mucosa, heretically without the involvement of lymphoid tissue (2). Incredibly, the implications of this are still not fully appreciated by the medical community, so the importance of IgE in allergy is often underestimated.

IgE, that can specifically recognise an "allergen" (typically this is a protein, such as dust mite DerP1, cat FelD1, grass or ragweed pollen, etc.) has a unique long-lived interaction with its high affinity receptor, Fc epsilon RI, so that basophils and mast cells, capable of mediating inflammatory reactions, become "primed", ready to release chemicals like histamine, leucotrienes and certain interleukins, which cause many of the symptoms we associate with allergy, such as airway constriction in asthma, local inflammation in eczema, increased mucus secretion in allergic rhinitis and increased vascular permeability, ostensibly to allow other immune cells to gain access to tissues, but which can lead to a potentially fatal drop in blood pressure as in anaphylaxis. Although the mechanisms of each response are fairly well understood, why some allergics develop such drastic sensitivities when others merely get a runny nose is still one of science's hot topics. Regulation of IgE levels through control of B cell differentiation to antibody-secreting plasma cells is thought to involve the "low affinity" receptor, Fc epsilon RII or CD23. CD23 may also allow facilitated antigen presentation, an IgE-dependent mechanism whereby B cells expressing CD23 are able to present allergen to (and stimulate) specific T helper cells, causing the perpetuation of a Th2 response, one of the hallmarks of which is the production of more antibodies.

Removal of foods causing IgG immune response as measured using the ELISA food panel has been shown to substantially decrease symptoms of Irritable Bowel Syndrome in a several controlled studies. (3)

ABH secretors tend to have higher levels of IgE than non-secretors. (4)

In 155 asthmatic children we have studied the relationship between prick test positivity and a set of genetic factors previously found to be associated with bronchial asthma. Among these factors, MN system (p = 0.009) and age at onset of symptoms (p = 0.05) are the most important variables separating prick test negative from prick test positive children. MN and age at onset influence independently prick test positivity pointing to an additive effect of the two variables. M phenotype appears correlated positively with an increased susceptibility to nonallergic asthma in all age groups, whereas N phenotype appears correlated positively with age at onset but in allergic asthma only. The MN system codifies for glycophorin A, a sialoglycoprotein that represents a major ligand for several bacteria and viruses that recognize the N-acetylneuraminic acid present in this protein. The present data suggest that genetic variability in this system might influence bacterial and viral competition and mucosal damage influencing susceptibility to asthmatic reactions in absence of IgE hyperproduction.(5)

Abstracts

References

Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes.

J Allergy Clin Immunol. 2005 Jan;115(1):80-7. Pykalainen M, Kinos R, Valkonen S, Rydman P, Kilpelainen M, Laitinen LA, Karjalainen J, Nieminen M, Hurme M, Kere J, Laitinen T, Lahesmaa R.

  • BACKGROUND: Immune responses characterized by T H 2 type cells and IgE are important for the development of asthma and atopy. The transcription factors STAT6, GATA3, and STAT4 mediate the cytokine-induced development of naive CD4 + T cells into either T H 1 or T H 2 type. OBJECTIVE: We studied genetic variation of the STAT6, GATA3, and STAT4 genes and examined whether single nucleotide polymorphisms (SNPs) in these loci were associated with asthma or serum high IgE levels in the Finnish asthmatic families. METHODS: With denaturing high-performance liquid chromatography we screened all exons and exon-intron boundaries of the genes in 14 to 22 patients. All identified SNPs were genotyped in 120 nuclear families, and the haplotypes were analyzed by Haplotype Pattern Mining based statistical analysis. When potential association was observed, the analysis was replicated among 245 asthmatic patients and 405 population-based control subjects. RESULTS: A total of 23 SNPs were identified, of which 8 were not previously listed in the SNP database. Interestingly, a haplotype analysis of GATA3 showed 3 related haplotypes that associated with different asthma and atopy related phenotypes among both the family and case-control data sets. For STAT6 and STAT4, no significant association to asthma or serum total IgE levels was observed. CONCLUSIONS: We identified a panel of novel SNPs in genes coding for proteins important in the T H 1/T H 2 cell differentiation. SNPs of the GATA3 gene showed an initial association to asthma-related phenotypes. Elucidation of the importance of the identified panel of SNPs in other T H 1/T H 2 mediated diseases will be of great interest.

Attribution

References


1. European Journal of Immunology 2003 Apr;33(4):1030-40.

2. Journal of Immunology 2005 Apr 15;174(8):5024-32.

3. (Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut 2004; 53(10):1459-64.

4. Grundbacher FJ Causes of variation in serum IgE levels in normal populations. J Allergy Clin Immunol 1975 Aug;56(2):104-11

5. Bottini N, Ronchetti F, Gloria-Bottini F, Stefanini L, Bottini E, Lucarini N.Atopic and nonatopic asthma in children.J Asthma. 2005 Feb;42(1):25-8.

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