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What is Gluten and Dairy Intolerance? What is the difference between an allergy and intolerance/sensitivity. Latest medical research. Open to the public.
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TOPIC: HLA-DQB1 gene, in IgA deficiency

HLA-DQB1 gene, in IgA deficiency 04 Apr 2007 17:08 #521

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It's an older article, but significant in it's finding of autoimmunity:

1: Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10653-7

Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency. Center for BioTechnology, Karolinska Institute, NOVUM, Huddinge, Sweden.

Most cases of selective IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) occur sporadically. However, familial clustering is not uncommon, and the two disorders can occur within the same family. We have previously described positive associations with three DR-DQ haplotypes as well as a strong negative association with DRw15,DQw6,Dw2 in IgA-D. Different amino acids at position 57 of the HLA-DQ beta chain were found to be related to susceptibility and resistance to IgA-D. Now we have found identical, although somewhat weaker, positive and negative DR-DQ associations in a large group of CVID patients (n = 86), as well as the same associations with codon 57 of the DQB1 gene. In addition, we have confirmed our earlier observations in an independent group of IgA-D individuals (n = 69), and in sib-pair analysis we have found linkage of the genetic susceptibility to IgA-D to the HLA class II region. In IgA-D individuals not carrying the three overrepresented DR-DQ haplotypes, the same positive association with a non-aspartic acid residue at position 57 of the HLA-DQ beta chain was seen. The previously reported associations with deletions of the HLA class III genes C4A (fourth component of complement) and CYP21P (steroid 21-hydroxylase pseudogene) were, in our groups of immunodeficient individuals, statistically secondary to the association with the DQB1 allele 0201.

The shared HLA class II associations in the two humoral immunodeficiencies support the hypothesis that IgA-D and CVID are related disorders. Disease susceptibility and resistance are most closely associated with a gene(s) within the DR-DQ region, alleles of the DQB1 locus being candidate genes.

PMID: 1438261 [PubMed - indexed for MEDLINE]

The full text article is available here:

http://www.pnas.org/cgi/reprint/89/22/10653

HLA-DQB1 gene, in IgA deficiency 06 Apr 2007 21:42 #522

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Hi Debra,

Thank you for posting this. I guess it is my case. But what does it really mean aside from my susceptibility to frequent bronchial infections and the dire need to stop smoking?

Does it say anything more about what kind of complications I might expect to find?

Alex

HLA-DQB1 gene, in IgA deficiency 07 Apr 2007 00:21 #523

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Hi Alex,

Yes, unfortuantely you are more suseptible to infection and respiratory problems.

This information might be more helpful:

Definition:
Selective deficiency of IgA is defined as low levels of or complete absence of immune globulin A, which causes decreased immune function in the mucosal surfaces (e.g., mouth, gastrointestinal tract , and lungs) and results in increased risk for respiratory and gastrointestinal infections . It is associated with autoimmune diseases .

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autosomal dominant (requiring only one parent to pass down the defective gene) or recessive (requiring defective genes from both) trait and is found in approximately 1 in 700 individuals of European origin. It is less common in people of other ethnicities.

Affected people often have chronic diarrhea caused by intestinal infections, frequent respiratory infections. Many develop autoimmune diseases like rheumatoid arthritis and lupus erythematosus .


HLA-DQB1 gene, in IgA deficiency 07 Apr 2007 08:07 #524

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Thank you, Debra. Now I finally understand the implications of this. Yep, that is me. Is there any way to produce those antibodies or to teach the body to produce them?

HLA-DQB1 gene, in IgA deficiency 07 Apr 2007 08:29 #525

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D, Can you explain the significance of this for me? I'll bold the parts that require inquiry and explanation. Thanks in advance, A

url=http://emedicine.com/med/topic216.htm emedicine.com/med/topic216.htm ][/url] The primary defect in selective IgA deficiency is related to a failure of B cells to differentiate to mature isotype-switched surface IgA-positive B cells and IgA-secreting plasma cells with appropriate stimuli. The basis for the defect is not known. B cells from patients with IgA deficiency activated via CD40 and interleukin-10 are capable of synthesizing and secreting IgA. Defective helper T-cell and excessive suppressor T-cell activities are occasionally present. Cytokine abnormalities have also been described.

Debra's comments: What this is saying basically is regular B cells taken from someone with IgA deficiency were able to to produce the immunogloblin IgA, but the T-cells that were produced were defective. But it's CD40 and interleukin derivitives that turn off the immune response when the T-cells and killer cells have usually done their job. You'll need to take a biology course to understand how cells differentiate, I really like this website : http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Treg.html#TrCells


IgG2 is the most common of IgG subclass deficiencies. It occurs either alone or with IgG4 or IgA deficiency. Its hallmark is an inability to generate antibodies to polysaccharides. 

Alex, you would have to be specifically tested for these subclass immunogloblins to make sure they were malfunctioning. But with as often as you get sick, my guess is that you're not producing these either.


Primary B-cell disorders result in a complete or partial absence of one or more immunoglobulin isotypes. Regardless of the primary cause, the symptoms depend on the type and severity of the immunoglobulin deficiency and the association of cell-mediated immunodeficiency. In general, severe immunoglobulin deficiency results in recurrent infections with specific microorganisms in certain anatomical sites.
Immunoglobulins play a dual role in the immune response by recognizing foreign antigens and triggering a biological response that culminates in the elimination of the antigen. Their role in the fight against bacterial infections has been recognized for many years. Emerging evidence from animal and clinical studies suggests a more important role for humoral immunity in the response to viral infections than what was initially thought.
IgM plays a pivotal role in the primary immune response. IgG is the major component, comprising approximately 85% of serum antibodies. They mediate many functions, including antibody-dependent cell-mediated cytotoxicity, phagocytosis, and clearance of immune complexes, by binding to the Fc receptors. IgG1 is the major component of the response to protein antigens (eg, antitetanus/diphtheria antibodies). IgG2 is produced in response to polysaccharide antigens (eg, antipneumococcal antibodies), and IgG3 seems to play an important role in the response to respiratory viruses. Each of these immunogloblins does a different job in fighting viral and bacteria infections.

Complement fixation and activation are carried out by IgG1, IgG3, IgM, and, to a lesser degree, IgG2. IgA and, to a lesser extent, IgM, produced locally and secreted in the secretions of mucous membranes, are the major determinants of mucosal immunity.
IgG antibodies are the only immunoglobulin class that crosses the placenta and provides the infant with effective humoral immunity during the first 7-9 months of life.

I think if you want to know more about you're specific defiencies you should see if you can find someone in LA who works in the field of immunogeniology. I might contact UCLA school of medicine and see if there's a study going on.

HLA-DQB1 gene, in IgA deficiency 07 Apr 2007 23:17 #526

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FYI: My IgA1 and IgA serum are low. IgG1 and IgG4 are low.

My  TIBC is high. What does that indicate?

I'll definately ask my doctor about these and also look into the research being done at UCLA. I feel like we've just peeled another layer in this onion that is my health. Thank you.

A

HLA-DQB1 gene, in IgA deficiency 01 May 2007 02:55 #527

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HI, Funny I should come upon this. Our celiac group had a pediactric gastro doc in the meeting last week and one of his comments was that if the IgA is lower then 5, then celiac won't be detected. IgA apparently helps IgG and EmA some how.
Nicole

HLA-DQB1 gene, in IgA deficiency 01 May 2007 02:56 #528

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OH, I was also going to say, my last blood work showed my IgA as 3 and my youngest brother does have IgA defiency. Food for thought.
Nicole

HLA-DQB1 gene, in IgA deficiency 01 May 2007 11:45 #529

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Hi Nicole

You your brother and  Alex are all IgA deficient (1 in 500 people) which is less common than Celiacs but you all must stay strictly gluten free as you know. If you're brother isn't on a gluten-free diet yet he should be. Yes, IgA deficiency is the main reason current Celiac blood tests don't work. You must first produce the immunoglobulin in order to produce the antibodies they test for.

I'm so glad you're learning from your group meetings, it sounds like you're going to a good one if they bring in a doctor (ped) who is knowledgeable enough to talk about IgA deficiency.

How's you IgG?

HLA-DQB1 gene, in IgA deficiency 01 May 2007 17:14 #530

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I'll try to find my newest paper work and take a look, I don't remember. I'm trying to pack for a vacation in Floriday for a week, so I"ll do it next week.
Nicole
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