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Thread: HLA types and autoimmune diseases

  1. #1
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    Post HLA types and autoimmune diseases

    Introduction

    Most people know their ABO blood type. In some countries people carry a card indicating their blood type, in case of accident requiring an emergency blood transfusion. Few people however have heard of HLA types (human leukocyte antigens), the antigens in our blood that fight off microbes.

    Contrarily to ABO blood types people do not have just one HLA type, but many (about 8 per person).

    There are 3 major types of class I HLA (HLA-A, HLA-B, HLA-C) and 3 major types of class II HLA (HLA-DP, HLA-DQ and HLA-DR). Each type comprises hundreds of subtype (e.g. HLA-B27), further subdivided in hundreds of sub-subtypes (e.g. HLA-B*2705).

    People will usually have 2 types of HLA-A, 2 of HLA-B, and 2 of HLA-C as well as 1 or 2 other types.

    HLA types are encoded in the HLA gene on chromosome 6. HLA types are therefore hereditary, just like the ABO blood type.

    HLA's role in fighting diseases

    Each type and subtype is more or less efficient in fighting off viruses and noxious bacteria. There are tens of thousands of possible combinations of HLA, which is why some people never get sick, while other constantly have a cold, or are prone to some types of infections, depending on what HLA combination they have.

    HLA types found in tropical countries tend to differ a lot from those in temperate parts of the world, because the viruses found there are different. Some Africans have developed HLA that give them resistance to malaria, for instance. When the Europeans arrived in the Americas, bringing with them new viruses on the continent, the biggest part of the Native American population of North America was wiped out as they didn't have the right antigens to fight off even the common cold.

    But too aggressive HLA's can also be bad for the body. Some HLA types are known to attack the body's own cells, causing what is known as autoimmune diseases, in other words diseases caused by one's immune system attacking one's own body.

    Autoimmune diseases linked to HLA types

    Here are a few known or suspected associations between HLA types and autoimmune conditions :

    Ankylosing spondylitis (arthritis of the spine and sacroiliac joint) : caused by HLA-B27 in 95% of the cases. The combination HLA-B7/B*2705 heterozygotes exhibited the highest risk for disease.

    Celiac disease (gluten allergy) : 95% of all celiacs have HLA-DQ2. 12% have HLA-DQ8.

    Diabetes : The HLA types DR2, DR6 and DR11 are protective against Type 1 diabetes. The risk alleles are DR3, DR4 and DQ2.5. DR3 is linked to late-onset, whereas carriers of DR4 are at risk for early-onset Type 1 diabetes. People who carry both DR3 and DR4 types are at the highest risk and will develop diabetes the youngest.

    HLA's play a lesser role in Type 2 diabetes. There is a suspected link with HLA-Cw4, DR7, DR11 and DQA1, among others.

    Graves' disease : HLA-DR3 plays a significant role in the disease.

    Hashimoto's thyroiditis : strongly associated with HLA-DR5.

    Lupus : weakly associated with HLA DR3, DR4, DR15 and DQA1.

    Multiple Sclerosis : HLA-DRB1*1501 plays a role in the disease.

    Myasthenia gravis : the main risk factors are HLA B8 and DR3 with DR1.

    Narcolepsy : strongly associated with HLA-DQB1*0602. There is also an association with HLA DR2 and HLA DQ1.

    Psoriasis : HLA-Cw*0602 is the main risk factor. HLA DR1 and DR7 may also play a role.

    Rheumatoid Arthritis : HLA DR1, DR4, DR5, DR8 and DR12 are associated with the disease at various levels.



    N.B. : HLA-DR11 is the short spelling for HLA-DRB1*11, just like HLA-C6 is short for HLA-Cw*06.
    Last edited by Maciamo; 18-11-08 at 14:50.
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    Here is a very useful website that gives HLA allelle frequencies in worldwide populations (must be registered). Data can be sorted by region, country, ethnicity and allele frequency. It's a good way of finding out in where your HLA types originated.

  3. #3
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    Too bad the link isn't available anymore...

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    I found these...

    For those who have their genomes, I found these 3 SNP's that correspond to HLA's

    Rs3135388 (T) HLA-DRB1*1501 allele M.S.
    Rs1265159 (A) HLA-Cw*0602 Psoriasis
    Rs27044 (GG or CG) HLA-B*2705 Anklosing Spondylitis

    I couldn't (easily) find others, but 23andme and deCODEme do report on many of those conditions. Personally, I have no increased risk for any autoimmune diseases, which frankly surprised me.

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    Hello,

    I joined this forum because I saw this post and wanted to ask a question about this
    information "Rs27044 (GG or CG) HLA-B*2705 Anklosing Spondylitis "
    Does this mean if one is GG or CG at Rs27044 they are HLA-B*2705 or does it mean it complicates it if they are also that HLA?

    If someone has CG at Rs 27044 are they a form of HLA-B27?

    Is there any SNP that tell you you are HLA-B27 or not?
    Thanks,
    Brian

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    Rs27044 and B27

    According to SNPedia:

    The rs27044 Variant Is Associated with HLA-B*2705 Subtype in Hungarian Patients with Ankylosing Spondylitis
    Retrieved from "http://www.snpedia.com/index.php/Rs27044"

    Also per SNPedia:


    HLA-B27, the first and still most prominent association
    • Over 40 allelic variants are known, the most common being B2705

    Ergo, I believe that HLA-B*2705 is a variant of HLA-B27. There are many other SNP's related to Ankylosing Spondylitis however. Hope this helps!

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    Thanks for the informative introduction. I just starting to do research on HLA. I have a case where the individual had done the HLA typing, but i do not understand how to read the genotype, whether is it locus, which nucleotide in the sequence etc.

    HLA-A typing : A*24:02/69-74/76-80/83N-87/90N-91/95-99 (A*24:GHXU)
    A*31:01/11-12/14N-17/19-20/23 (A*31:FZST)
    HLA-B typing : B*07:02/29/41/61 (No Code)
    B*54:01/07-08N/10/12-14 (B*54:FTBR)
    HLA-C typing : C*07:02/56/61N-62/64/66-67/72/74 (C*07:FZSG)
    C*08:01
    HLA-DR typing : DRB1*04:05/45/57 (DRB1*04:CRUA)
    DRB1*07:01/08-17 (DRB1*07:FTBS)

    What is the / mean? where can i learn more about the naming? how can i picture it where is it located in the sequence shows in NCBI? thank you.

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    I've wondered when the genetic link for inherited auto immune diseases would be found. I have inherited Type II diabetes and Rheumatoid Arthritis. A number of people in my immediate family suffer from both of these conditions.
    I know my basic blood type as B II positive, but not down to the levels here. Unfortunately I don't yet have a completed DNA results from FTDNA so I can only look to my 67 marker Y DNA results for any clues. Since my paternal grandmother is the apparent souce of both the diabetes and RA, I doubt that I am going to see it in my Y analysis.
    I will admit to being a rank amateur when it comes to understanding what this all means but I do enjoy speculating.

  9. #9
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    Thanks for sharing.. i was looking those points..

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