Do you know about - Celiac Genetic Tests Are Not All Equal and Some Dq2 Negatives May Not Be thoroughly Negative
Labcorp Laboratories! Again, for I know. Ready to share new things that are useful. You and your friends.Genetic tests exist for Celiac disease and are highly definite for determining the risk of the disease. When a perfect genetic panel is performed the possibility that man having or ever getting this autoimmune disease can be thought about to an highly high degree of certainty. Unfortunately, some tests are misleading because they do not comprise a measure of the genetic pattern that may be present that can predispose to this gluten sensitivity disease though the description may imply absence of increased risk.
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Some genetic tests can be done without a doctor's order. Assurance coverage for the Celiac genetics is highly variable. A couple of laboratories can run the tests on samples obtained from a mouth swab that is painless and well thorough by children. Genetic testing can be done at any age while blood tests for Celiac are not recommended before a year of age. Celiac genetic tests are not affected by eating gluten or not.
If you do not have the generally recognized Hla genetic patterns Dq2 or Dq8 that are connected with Celiac disease you are believed to not be at risk for the full autoimmune disease. You don't need to be periodically retested. However, you still could be intolerant or sensitive to gluten. Knowing your genetics can be very helpful if you have a house member with Celiac disease or they or you have other autoimmune diseases connected with a risk of Celiac.
Hla Dq2 and Dq8 are the simple designations for involved white blood cell patterns or types that are known to be connected with an growth risk of Celiac disease. The Hla term stands for human leukocyte antigen. Leukocytes are white blood cells. Antigens are proteins that serve or elicit an immune response by the body. So, the Hla ideas is a involved set of proteins on the face of white blood cells. Everybody has two copies of a Dq protein pattern. You get one copy of Dq from your mom and one from your dad. Having at least one copy of whether is primary and sufficient to invent the disease. Having two copies of whether or one of both increases the risk even more.
These protein patterns are inherited just like the red blood cell proteins that constitute what is generally known your "blood type". I, for example, am A clear blood type. This means I have a pattern of proteins designated A and Rh+ on the face of my red blood cells. On the other hand I have a white blood cell type pattern Dq2/Dq7 inherited from my parents. My Dad gave me a Dq2 and my Mom the Dq7. You have two Dq patterns on your white blood cells that you received from your parents and you give one of your Dq types to each of your children.
Since only a single copy of whether Dq2 or Dq8 can be connected with an growth risk of developing Celiac disease, most laboratories test for the presence of whether and plainly description their presence or absence. However, knowing if you have one or two copies not only provides further facts about degree of your risk. It also may predict the severity. It also provides facts about your parents and your childrens' risk of inheriting an at risk gene. If you have Dq2 and Dq8 we know your perfect Dq pattern. We also known one of your parents had at least Dq2 and the other Dq8. All of your children will whether get a Dq2 or a Dq8. So, both your parents and all of your children are at risk for Celiac in that situation. If you have only copy of Dq2 or Dq8 then we only know that at least one of your parents had one copy of the risk gene and each of your children will have a 50-50 occasion of inheriting such a risk gene from you.
Other non-Hla genetic factors are involved in the risk of celiac disease. These are still being worked out. However, one poorly understood and dinky known fact to most doctors and approximately all patients is that Hla Dq2 and Dq8 testing done by some laboratories does not comprise the full spectrum of at risk components of these patterns. Dq2 and Dq8 are a summary blood type designations or serotypes for the presence of any protein subunits. There are alpha and beta subunits to these protein patterns. The beta subunit is the most influential and prominent component. Most laboratories only test for and description the beta subunit. However, the alpha subunit does carry risk on its own, albeit much less than the presence of the beta subunit or the presence of both alpha and beta subunit.
The most generally used laboratories for celiac disease genetic testing in the U.S. Are Kimball Genetics, LabCorp, Quest, Prometheus, and Enterolab. The Laboratory at Bonfils in Denver not only provides testing directly but also does the testing for any hospitals, Quest and Enterolab. Bonfils only does beta subunit testing. They description results of Dq2 and Dq8 negative based on the absence of the beta subunits connected with Dq2 and Dq8. Any way this is somewhat misleading since man could have only the alpha subunit and be "partially" Dq2.
Though the risk of being "half" Dq2 clear from only having the alpha subunit is low allinclusive it is still there. Furthermore, there are citizen who may believe that they are Dq2 or Dq8 negative based on testing from Bonfils, Quest or Enterolab. These citizen and/or their doctor may exclude the possibility that they have or are at risk for ever getting Celiac disease when in fact this may or may not be true.
The existence of Dq2 and Dq8 negative Celiac disease has been debated. It is probably clouded to some degree by this blurring about the genetics. Most experts claim that the presence of Dq2 or Dq8 is a requirement to invent the disease and their absence excludes the possibility. However, reports of Dq2 and Dq8 negative Celiac disease persist.
I have a couple of patients who have the clear results for the exact blood tests for Cd, endomysial or tissue transglutaminase antibody; and superior biopsy features but were reported Dq2 and Dq8 negative by laboratories who only test for the beta subunit. Ideally, they should be re-testing for alpha unit clear "half" Dq2 or Dq8 but this will depend on their Assurance coverage. In the meantime, I am remain implicated that many patients and doctors may be lulled into a false sense of protection by negative genetic tests incompletely done or that diagnoses of Celiac disease may be or have been withdrawn on some individuals based on incomplete genetic results.
This issue of Dq2 and Dq8 testing is further involved by reviews on the branch that are incomplete or vague. The best reviews I have found are by Ludvig Sollid and Benedicte Lie of Oslo, Norway "Celiac Genetics: Current Concepts and Practical Applications" Clinical Gastroenterology and Hepatology 2005 and Bourgey's 2007 review. In a recent modernize description by Victorien, there is a general retell the genetics of celiac disease together with the association of myosin Ixb gene (Myo9B). However, it doesn't elaborate the Dq2 or Dq8 typing well. They stop that "To date, only Hla-Dq2 or Hla-Dq8 typing is clinically relevant..." but fail to point out that Hla Dq2 and Dq8 typing should comprise both alpha and beta subunits.
It is clear that both Hla and non-Hla genetic factors are prominent in the risk of Celiac disease. However, the absence of the high-risk genes does not preclude adverse reactions to gluten together with leaky gut, skin, digestive and neurological symptoms. When genetic testing is used to try to correlate the risk or exclude Cd then I recommend that full testing together with both alpha and beta subunit typing. Hopefully more explore will better define the genetics of both Celiac disease as well as non-celiac gluten sensitivity or the so called "gluten syndrome".
Selected References:
Bourgey, M et al. Hla connected genetic risk for Coeliac disease. Gut 2007; 56:1054-1059.
Johnson, Tc et al. association of Hla-Dq8 and severity of Celiac disease: Comparison of New York and Parisian cohorts. Clin Gastroenterol Hep 2004; 2:888-894.
Kaukinen K. Et al. Hla-Dq typing in the pathology of Celiac disease. Am J Gastroenterol 2002; 97(3): 695-699.
Lundin, Ke. Hla-Dq8 as an Ir gene in Coeliac disease. Gut 2003; 52:7-8
Mazzarella G. Et al. An immunodominant Dq8 restricted gliadin peptide activates small intestine immune response in in vitro cultured mucosa from Hla-Dq8 clear but not Hla-Dq8 negative Coeliac patients. Gut 2003; 52:57-62.
Sollid, Lm and Lie, Ba. Celiac disease genetics: Current concepts and practical applications. Clin Gastro Hep 2005; 3:843-851.
Wolters,Vm and Wijenga C. Genetic background of celiac disease and its clinical applications. Am J Gastroenterol 2008; 103:190-195.
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