Do you know celiac disease occurs from genetic as well as non-genetic factors? Well, celiac disease happens when human leukocyte antigen or HLA genes HLA DQ2 and DQ8 seem to be the strongest genetic susceptibility. But only 1% of the entire population are diagnosed through celiac disease which denotes other factors are there in complicated genetic disorder progression.
HLA genetic test helps to diagnose celiac disease and detect the condition in family members who might be at greater risk. The present process of HLA genetic test when performing celiac disease has lower positive predictive value. So, the clinicians can gain keen understanding of when HLA genetic testing needs to be ordered, the kind of test which should be ordered and how you can interpret test results.
Some features of HLA
The genes determining HLA molecules are present in major histocompatibility complex or MHC on chromosome 6. Each HLA locus consists of several known alleles and the new alleles can be characterized constantly. The presence of HLA loci in celiac disease will be in class II region at DQ locus while HLA-DQA1 and DQB1 loci code relate to heterodimers on antigen-presenting cells surface. These protein heterodimers are what you popularly call HLA-DQ molecules.
The method of knowing which proteins or alleles will be there in patient is called “HLA typing.” In order to find out HLA heterodimer, the loci encoding for specific heterodimer should be typed (for celiac disease, DQA1 and DQB1 in case of DQ protein). The laboratories use molecular nomenclature and prefer HLA with molecular procedures.
There may be around 4 different heterodimers in patients as each person sets 2 alleles for each DQA1 and DQB1 loci. So, a heterodimer fixed by alleles on same chromosome can be cis-encoded while a heterodimer created from the alleles on opposite chromosomes will be trans-encoded. Compatible heterodimers which are trans- or cis-encoded can express the functional molecules. Hence, the contemporary testing for celiac disease types DQA1 and DQB1 loci.
HLA DQ2 and DQ8 testing in UK has a vital role in developing celiac disease. HLA-DQ2 and DQ8 may present gluten-derived peptides in comparison to other HLA kinds. Inflammation is generally triggered through pathogenic method where antigen-presenting cells connect to DQ8 or HLA-DQ2.
According to the researchers, the genetics of HLA types adding to celiac disease are somewhat complicated as the risks can be determined by the configuration of DQA1 and DQB1 alleles. The constituent parts of HLA genetics and how they combine to enhance risk for celiac disease have been discussed below.
- HLA-DQ2.5: This variant of DQ2 molecule can be set by about 90% of patients who suffer from celiac disease. HLA-DQ2.5 is usually encoded by the alleles of DQB1*02 and DQA1*05. The DQ2.5 heterodimer may either be trans-encoded or cis-encoded.
- HLA-DQ8: The DQ8 protein is there in around 20% of patients who have celiac disease. The HLA-DQ8 heterodimer can be set by alleles of DQB1*03:02 and DQA1*03.
- HLA-DQ2.2: This heterodimer will be there in 35% of patients suffering from celiac disease. The DQA chain of this heterodimer can be set by an allele of DQA1*02 than DQA1*05 allele.
When you need to order for HLA genetic testing
As per researchers, many clinical scenarios are there where HLA genetic tests are done. HLA testing may exclude celiac disease in patients who suffer from the symptoms after starting their gluten-free diet. This can detect patients who are at greater risk for celiac disease due to family history.
HLA tests might be of great help for patients who have tested negative for HLA DQ2 and DQ8 blood testing. The clinicians need to determine whether HLA testing benefits on first-degree relatives may outweigh the costs associated with it.
What HLA test you should order
The clinicians need to order HLA-DQA1 and DQB1 to verify celiac disease. Patients who perform HLA typing should be tested only once during their lifetime as the test is genetic and patients’ genetic status won’t change over time.
How to interpret HLA test results
DQA1 and DQB1 can be typed in HLA genetic testing while clinical obtain the test results which denote if HLA-DQ2 or DQ8 are present or not. If neither of the alleles has been detected, the clinicians might rule out celiac disease, as patients who don’t set the alleles are at greater risk for the disease. If a patient is positive for DQ8 or DQ2, this means he/she is tolerant for celiac disease and can develop this ailment. Make sure you ask your provider about DQ8 testing cost when you decide to perform it.
The risks for getting celiac disease in patients who have been positive for DQ8 or DQ2 are determined depending on the molecules to be set. While DQ2.5 is highly associated with celiac disease, DQ2.2 and DQ8 are related to lower risk. But patients who encode two of these molecules will probably develop celiac disease. Besides, patients with DQ2.5 will have severe celiac disease symptoms.
Thus, the Private Blood Tests London clinicians should consider three guidelines at the time of conducting HLA test for celiac disease. Firstly, the clinicians need to ensure the laboratory is typing and reporting both DQA1 and DQB1 loci in molecular nomenclature. Secondly, the clinicians should consider positive result of DQ2.5, DQ2.2 or DQ8. Thirdly, the clinicians need to know that celiac disease can be ruled out in both DQ2 and DQ8. The presence of DQ8 or DQ2 might denote a risk but cannot be used to diagnose celiac disease.
