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Confused about Lewis...  This thread currently has 2,866 views. Print Print Thread
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Ronagon
Thursday, August 16, 2007, 10:49am Report to Moderator Report to Moderator
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Okay, I understand what you're thinking now.  It just might be right.

But a different thought just occurred to me:  When the "Se" enzyme produces that H type 1 antigen, is that just the secreted blood type O molecule?  After all, it looks the same, right?  Does that set of pathways produce ALL blood type antigens, or only the secreted versions?

And if that's the case, is the non-secreted form, though identical, produced through the actions of a completely different gene at chromosomal site 9q34, rather than the secreted form, which is produced at either chromosome 11 or the other one?  Is it really the case that both the secreted and non-secreted forms of all the various blood type antigens are chemically indistinguishable from each other, even though they're produced at two different chromosomal sites?

If so, that's pretty interesting.

Revision History (3 edits)
Ronagon  -  Thursday, August 16, 2007, 11:00am
Ronagon  -  Thursday, August 16, 2007, 10:54am
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Ronagon
Thursday, August 16, 2007, 11:12am Report to Moderator Report to Moderator
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You know, after sifting through all these various diagrams, struggling through the published explanations, and talking this through with each you (which I'm very grateful to you for doing with me, by the way...), I've come to the conclusion that this was a very, very difficult and complicated pathway to grasp before we even started, and merely trying to describe it in words, is not nearly adequate.

To really make this clear, requires a full, pictorial diagram of some clarity and quality.

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Ronagon  -  Thursday, August 16, 2007, 11:14am
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yaman
Thursday, August 16, 2007, 11:22am Report to Moderator Report to Moderator

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The miracle of Life, is never simple Ron even though you have started with what at first glance seemed to have a simple answer.

Hopefully other minds will join this exciting thread..



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Ronagon
Thursday, August 16, 2007, 11:31am Report to Moderator Report to Moderator
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I've just been looking through this link for the book, "Essentials of Glycobiology", and it has some really amazing diagrams of all kinds of glycoconjugate molecules:

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=glyco

In fact, there are a number of informative books at that website:

http://www.ncbi.nlm.nih.gov/books

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Ronagon  -  Thursday, August 16, 2007, 11:33am
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Ronagon
Thursday, August 16, 2007, 11:48am Report to Moderator Report to Moderator
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And so, my final understanding here is as follows:

1) All secreted blood type antigens (A, B, and O), as well as Lewis antigens A and B, begin as "Type I" compounds.

2) This type I compound is added upon by the secretor gene, to create the to-be-secreted "H" antigen (also known as the "O secretor" antigen, which is, of course, secreted).

3) This to-be-secreted "H" antigen is added upon by the Lewis enzyme to create the Lewis "B" antigen, which is also secreted.

4) The original "Type I" compound (from "1)") can also be added upon by that same Lewis enzyme, to yield the Lewis "A" antigen, which is not secreted.

5) The "H" antigen (also known as the "O secretor" antigen, from "2)") can be added upon by the ABO gene at 9q34 to yield either an "A Secretor" or "B Secretor" antigen, which, as the names imply, are secreted.

6) In the case of the non-secreted blood types, the "H" antigen which is to be used as the base to build the non-secretor A's, B's, and O's, is made elsewhere, by some gene besides the secretor gene, though the structure will be identical.  However, the ABO gene at 9q34 will still attach the "A" and "B" molecules to form the non-secretor "A" and "B", just as they did with the to-be-secreted forms.

If I've got this all right, I'm astonished... and a little relieved, at last.

Revision History (3 edits)
Ronagon  -  Thursday, August 16, 2007, 11:54am
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yaman
Thursday, August 16, 2007, 12:13pm Report to Moderator Report to Moderator

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I'm afraid I have argue the point 1

In the first link you've provided above, it says that there are actually four typs of precursors to the ABO blood groups.

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=glyco.section.1068


"You are never given a problem without the will power to solve it"
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Lola
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http://www.ncbi.nlm.nih.gov/projects/mhc/xslcgi.fcgi?cmd=bgmut/systems_info&system=lewis
gosh guys, hope you reach a verdict!!
I m trying to learn something here!!! lol
http://www.dadamo.com/wiki/wiki.pl/Lewis_Blood_Group

Quoted Text
A Le(a+b+) phenotype may occur in individuals in whom the expression of H is decreased due to a mutation in the FUT2 gene (385A>T). This phenotype may also occur due to incomplete fucosylation of type H precursor sites. Failure to express FUT3 will result in a Lewis null phenotype [Le(a-b-)], irrespective of the Secretor status. However, one should note that the latter phenotype may also be observed upon the absence of Le glycolipids from the membrane, as may occur in patients with certain cancer or other conditions.

Quoted Text
Le(a+b+), is found in the Oriental population and appears to be due to a weak secretor gene.

Quoted Text
The le gene is an amorph. Persons who are lele produce no Lea and no Leb antigens. RBCs that type as Le(a+b+) are only rarely found when human antisera are used in typing. Such RBCs are seen more frequently when more potent monoclonal anti-Lea and anti-Leb reagents are used.

a rare bird!
http://www.dadamo.com/bloggers/ask/archives/00000234.htm


''Just follow the book, don't look for magic fixes to get you off the hook. Do the work.'' Dr.D.'98
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Ronagon  -  Thursday, August 16, 2007, 9:05pm
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Ronagon
Thursday, August 16, 2007, 10:56pm Report to Moderator Report to Moderator
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yaman,

Thanks for posting that.  I wonder if all those ABO variants still act as blood type antigens, in the same way.  Maybe they're created at different sites or something.



Lola,

Thanks for posting that.  I just realized that Dr. D has the same chart as was on that link yaman posted to me...
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Lola
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right!


''Just follow the book, don't look for magic fixes to get you off the hook. Do the work.'' Dr.D.'98
DNA mt/Haplo H; Y-chrom/J2(M172);ISTJ
The harder you are on yourself, the easier life will be on you!
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Don
Tuesday, August 21, 2007, 7:31pm Report to Moderator Report to Moderator

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Quoted from yaman
Lewis a-b- is a rare case,...

According to Dr. Kruzel in his 2003 IfHI presentation in the USA

Lewis a-b- = Whites 6%  Blacks 22%


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Don
Tuesday, August 21, 2007, 7:49pm Report to Moderator Report to Moderator

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Quoted from Ronagon
I've never been able to make logical sense of a few things regarding the Lewis antigen status thing...

1) What, precisely, do Lewis antigens do, whether secreted or otherwise?

Lewis is not secreted, only ABO is secreted.
The secretor factor (Se) might be considered either a physiologic trait or an honorary blood group. The individual who is a so-called secretor has demonstrable ABH blood group antigen in the saliva and other body fluids; the nonsecretor does not. Secretor is dominant.

Genetically independent of the ABO blood groups is the secretor system which comprises two allelomorphic genes, Se which causes secretion in saliva and other fluids of the antigen or antigens corresponding to the individual's ABO group, and se which, in the homozygous condition determines non-secretion. Heterozygotes are secretors.


Quoted from Ronagon
2) Are Lewis antigens measured through a blood test?  After all, if they were just measured with a saliva test, how would you be able to distinguish between a+b- and a-b-, when both would presumably still be bound on a non-secreted cell surface?

According to Dr. Kruzel in his 2003 IfHI presentation you use 1 drop of anti-LeA or anti-LeB in two test tubes to check for agglutination of LeA and LeB, respectively. If you don't find any agglutination in either test tube then that would represent Lewis a-b-.

Quoted from Ronagon
3) If one gene controls both Lewis antigen secretion AND blood type antigen secretion, then how is it possible that you could have a Lewis double-negative person who could also be either undetermined as a blood type secretor or non-secretor?  That seems like the action of an independent, though linked, gene or something...

See answer to 1 above. Lewis and secretor are 2 different, but somewhat related issues.
The synthesis of the epitopes is dependent on the interaction of two different fucosyltransferases, products of two different loci: FUT2 or the secretor (Se) locus of the H/h blood group system that encodes the alpha (1,2) fucosyltransferase (FUT2), and the FUT3 locus that encodes the alpha (1/3,1/4 fucosyltransferase (FUT3).
...
Clearly, the genotype of an individual at the FUT2 and FUT3 loci determines the Lewis phenotype. In the presence of FUT2 alleles that express type 1 H determinants, the phenotype will be Le (a-b+), but individuals in whom the FUT2 gene is not expressed, it will be Le(a+b-). A Le(a+b+) phenotype may occur in individuals in whom the expression of H is decreased due to a mutation in the FUT2 gene (385A>T). This phenotype may also occur due to incomplete fucosylation of type H precursor sites. Failure to express FUT3 will result in a Lewis null phenotype [Le(a-b-)], irrespective of the Secretor status.

I suggest you read at least the whole introduction section of the article.


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Don
Tuesday, August 21, 2007, 8:17pm Report to Moderator Report to Moderator

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Quoted from Ronagon
BOTH nonsecreted Lewis antigens AND secreted Lewis antigens at the same time.

I have already addressed the issue that secretor/non-secretor applies to ABH, not Lewis, in a previous post.



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Don
Tuesday, August 21, 2007, 8:19pm Report to Moderator Report to Moderator

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Quoted from Ronagon
And so, my final understanding here is as follows:

If I've got this all right, I'm astonished... and a little relieved, at last.

I think you need to go back and re-think all this.



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Don
Tuesday, August 21, 2007, 10:02pm Report to Moderator Report to Moderator

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Quoted from Ronagon
2) Are Lewis antigens measured through a blood test?  After all, if they were just measured with a saliva test, how would you be able to distinguish between a+b- and a-b-, when both would presumably still be bound on a non-secreted cell surface?

Here is a page that explains both the secretor saliva and Lewis blood testing procedures: DETERMINING SECRETOR STATUS


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Quoted Text
The way I understand is, it is about whether the ABH antigens being secreted or not, and not about secreting Lewis antigens.

as Yaman also mentioned in the second post of this thread......


''Just follow the book, don't look for magic fixes to get you off the hook. Do the work.'' Dr.D.'98
DNA mt/Haplo H; Y-chrom/J2(M172);ISTJ
The harder you are on yourself, the easier life will be on you!

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Ronagon  -  Tuesday, August 21, 2007, 10:21pm
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Tuesday, August 21, 2007, 10:44pm Report to Moderator Report to Moderator

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Quoted from lola

as Yaman also mentioned in the second post of this thread......

Yes, but Ron kept mentioning Lewis being secreted, so I thought it was worth repeating that secretor status applies to ABH being secreted, not Lewis.



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Wednesday, August 22, 2007, 2:46am Report to Moderator Report to Moderator

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right Don!


''Just follow the book, don't look for magic fixes to get you off the hook. Do the work.'' Dr.D.'98
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Hannah2
Wednesday, August 22, 2007, 4:44am Report to Moderator Report to Moderator
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I just received the results for the saliva test.. and  am happy with the secretor result.  I am confused about the suggestion to have confirmatory tests of Lewis blood group types.

I have read through  this thread  but I can't say I am any the wiser    
Is the saliva test as such  sufficient for me to tailor my diet around it, or are more tests needed?

The Lewis bit is new to me, and for some reason whatever I read about it, it doesn't seem to sink in..  funny sort of brain fog at the moment.

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Lola
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saliva test is quite accurate!
no need to do a blood test.


''Just follow the book, don't look for magic fixes to get you off the hook. Do the work.'' Dr.D.'98
DNA mt/Haplo H; Y-chrom/J2(M172);ISTJ
The harder you are on yourself, the easier life will be on you!
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Don
Wednesday, August 22, 2007, 1:22pm Report to Moderator Report to Moderator

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Quoted from lola
saliva test is quite accurate!
no need to do a blood test.

Agree, but let me just add that there is no reason to do the Lewis blood test unless you are considering doing SWAMI, then you might want to find out if you are Lewis a-b-, since that is an optional input.



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Quoted from Hannah2
I just received the results for the saliva test.. and  am happy with the secretor result.  I am confused about the suggestion to have confirmatory tests of Lewis blood group types.

The saliva test is the best way to determine secretor status.
Quoted from Hannah2
I have read through  this thread  but I can't say I am any the wiser    

I am not surprised. Much of what was posted in this thread was confusing and not necessarily exactly correct information about the Lewis type system.
Quoted from Hannah2
Is the saliva test as such  sufficient for me to tailor my diet around it, or are more tests needed?

The saliva test is sufficient for now. However, for SWAMI you might want to consider some additional testing and once the new Genotype Diet book comes out we may find out that there are additional tests that will help to individualize our diets.
Quoted from Hannah2
The Lewis bit is new to me, and for some reason whatever I read about it, it doesn't seem to sink in..  funny sort of brain fog at the moment.

The wiki articles on the topic are good. If you haven't already, you might want to read them sometime.


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Ronagon
Wednesday, August 22, 2007, 1:59pm Report to Moderator Report to Moderator
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Quoted Text
I am not surprised. Much of what was posted in this thread was confusing and not necessarily exactly correct information about the Lewis type system.


Well, my purpose in starting this thread was to try and figure things out, starting from an openly-declared state of confusion.  I even titled this thread to indicate that.  

I'm not sure how else I'm supposed to learn this stuff without asking questions...  

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Don
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Most definitely you get lots of points for discussing and trying to make sense of of it!


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Quoted Text
there is no reason to do the Lewis blood test unless you are considering doing SWAMI, then you might want to find out if you are Lewis a-b-, since that is an optional input.


and once that turns up positive, like in my case, then you do want to be double sure with the saliva test, right Don?

still haven t gotten around to it...unbelievable!!

a friend of mine in Barcelona who does allergy testing is now implementing the lewis test in her lab, after I convinced her on the importance of determining secretor status for her patients!!!
but down here, am still looking for a lab to transform. lol
slow wins the race!
I m about to meet some lab colleges of hers here in Mexico city, interested in the lewis test implementation.......it s a process, but well worth it!


''Just follow the book, don't look for magic fixes to get you off the hook. Do the work.'' Dr.D.'98
DNA mt/Haplo H; Y-chrom/J2(M172);ISTJ
The harder you are on yourself, the easier life will be on you!
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Don
Wednesday, August 22, 2007, 7:22pm Report to Moderator Report to Moderator

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Quoted from lola
and once that turns up positive, like in my case, then you do want to be double sure with the saliva test, right Don?

still haven t gotten around to it...unbelievable!!

a friend of mine in Barcelona who does allergy testing is now implementing the lewis test in her lab, after I convinced her on the importance of determining secretor status for her patients!!!
but down here, am still looking for a lab to transform. lol
slow wins the race!
I m about to meet some lab colleges of hers here in Mexico city, interested in the lewis test implementation.......it s a process, but well worth it!

You should have done your spitting at the IfHI conference and shipped it from there, but I guess you didn't know you were a Lewis (a-b-) then and would still needed to confirm your secretor status with the saliva secretor test.

Good luck on your work with the labs. After you convince them to do the Lewis test then you can start working on them to do the secretor saliva test too.


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