Coverage Policy Manual
Policy #: 2013016
Category: Laboratory
Initiated: June 2013
Last Review: June 2024
  Genetic Test: Celiac Disease, HLA Typing (HLA-DQ)

Description:
Celiac disease is currently diagnosed by serology, medical history, and response to a gluten-free diet with confirmation by small intestinal biopsy. Human leukocyte antigen (HLA) testing may be useful for ruling out disease in symptomatic patients when findings of other tests are inconclusive.
 
Celiac disease, also referred to as celiac sprue or gluten-sensitive enteropathy, is a relatively common disorder that has variable clinical expression. Population-based screening surveys suggest a worldwide prevalence of 1% with approximately 2 million in the U.S (National Institute of Diabetes and Digestive and Kidney Diseases, 2020). However, this prevalence may vary widely depending on how the disease is defined and whether only clinically apparent cases are considered, as opposed to including all individuals with any serologic or histologic evidence of disease.
 
Celiac disease is characterized by inflammation of the small intestine resulting from an immunologic intolerance to gluten (i.e., the proteins derived from wheat, barley, and rye). The symptoms of the disease are markedly variable and can be broadly subdivided into intestinal and extraintestinal manifestations; the latter is thought to be related to nutrient malabsorption. For example, osteopenia and osteoporosis, which are commonly seen in adults with untreated celiac disease, are related to the impaired absorption of vitamin D and binding of intraluminal calcium and magnesium to unabsorbed dietary fatty acids, forming insoluble soaps. The only treatment for celiac disease is lifelong adherence to a gluten-free diet.
 
Many of the symptoms of celiac disease (e.g., diarrhea, abdominal pain, and weight loss) are nonspecific and are often overlooked. In addition, the disease may develop at any time in life, from infancy to very old age. In children, the disease typically presents following weaning between 6 and 24 months, and is characterized by abnormal stools, poor appetite, and irritability. In adults, diarrhea is the main presenting symptom, but presenting symptoms may be entirely nonspecific, such as anemia or infertility. Typical or classical celiac disease refers to the presence of malabsorption, while atypical celiac disease consists primarily of extraintestinal manifestations.
 
Celiac disease is associated with the human leukocyte antigen (HLA). Approximately 90% to 95% of patients with celiac disease carry the HLA-DQ2 allele and the remaining 5% to 10% carry the HLA-DQ8 allele. However, not all people with one of these 2 alleles will develop celiac disease. It is believed that approximately 25% to 40% of the general population of the U.S. carries either the HLA-DQ2 or HLA-DQ8 allele but only about 3% of individuals carrying the DQ2/DQ8 alleles will develop gluten intolerance (Hadithi, 2010; Megiorni, 2012).
 
Given the nonspecific nature of the symptoms, the definitive diagnosis has been based on the results of small intestinal biopsies showing a flattened intestinal mucosa in association with an inflammatory infiltrate. Diagnostic criteria were first established in 1969 by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHN) and consisted of a series of 3 intestinal biopsies: one at diagnosis, one after institution of a gluten-free diet, and the third after a repeat gluten challenge. This cumbersome method of diagnosis was revised in 1990 by simplifying the diagnostic criteria to a positive biopsy at presentation in conjunction with consistent history and serologic results, followed by a clinical response to a gluten-free diet (Walker-Smith, 1990).
 
While a positive biopsy result is considered the criterion standard for diagnosis, the serologic evaluation of patients with possible celiac disease, together with a consistent clinical history and a positive response to a gluten-free diet, can sometimes be adequate for diagnosis. Serologic studies are also useful in triaging the large numbers of patients with nonspecific symptoms for biopsy. In approximately 10% of cases in which clinical suspicion suggests celiac disease, serologic testing, and intestinal biopsy are non-diagnostic, either because the results of serology and biopsy are discordant, or because both tests are negative despite persistent symptoms suggestive of celiac disease. In these cases, HLA testing may be useful for ruling out a diagnosis of celiac disease.
 
National guidelines and position statements recommend serologic testing as the first step in diagnosing CD and recommend the immunoglobulin (Ig) A antibody to human recombinant tissue transglutaminase test (NIH consensus development conference on celiac disease, 2004; AGA Institute, 2006; Hill, 2005; Rubio-Tapia, 2023). Guidelines have indicated that the IgA antibody to anti-endomysium antibody test has similar sensitivity and specificity as the tissue transglutaminase IgA test, but national organizations have indicated that the anti-endomysium antibody test is more prone to interpretation error. For subjects with known selective IgA deficiency, testing with tissue transglutaminase IgG and/or anti-endomysium antibody IgG is recommended.
 
Regulatory Status
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. Several methods are used for HLA typing including Simple Sequence-specific-Primer, Polymerase Chain Reaction (PCR), reverse dot blot hybridization, and real-time PCR. Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.

Policy/
Coverage:
Effective March 2021
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
HLA-DQ2 and HLA-DQ8 testing to rule out celiac disease testing meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes to rule out celiac disease in patients with discordant serologic and histologic (biopsy) findings or if persistent symptoms warrant testing despite negative serology and histology.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
HLA-DQ2 and HLA-DQ8 testing to rule out celiac disease in any other circumstance does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, HLA-DQ2 and HLA-DQ8 testing to rule out celiac disease in any other circumstance is considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective April 2013-March 2021
 
HLA-DQ2 and HLA-DQ8 testing to rule out celiac disease testing meets member benefit certificate primary coverage criteria to rule out celiac disease in patients with discordant serologic and histologic (biopsy) findings or if persistent symptoms warrant testing despite negative serology and histology.
 
HLA-DQ2 and HLA-DQ8 testing to rule out celiac disease in any other circumstance does not meet HLA-DQ2 and HLA-DQ8 testing to rule out celiac disease.
 
For members with contracts without primary coverage criteria, HLA-DQ2 and HLA-DQ8 testing to rule out celiac disease in any other circumstance is considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Rationale:
This policy was created with a literature search of the MEDLINE database through April 12, 2013. It was based in part on archived policy 2003056 Celiac Disease Antibody Testing. A summary of the key literature is as follows:
 
Serologic diagnosis in individuals with signs or symptoms suggestive of celiac disease
National guidelines and position statements agree that serologic testing is the first step in diagnosing celiac disease and that the IgA antibody to human recombinant tissue transglutaminase (tTG) test is recommended (NIH, 2004; AGA, 2006; Hill, 2005). They state that the IgA antibody to antiendomysium antibody (EMA) test has similar sensitivity and specificity to the tTG IgA test, but two of the national organizations mention that the EMA test is more prone to interpretation error. For individuals with known selective IgA deficiency, testing with tTG IgG and/or EMA IgG is recommended. The national organizations also agree that when test results are indeterminate, testing for the genetic markers HLA-DQ2 or HLA-DQ8 is recommended.
 
Several studies have established that HLA typing has a high sensitivity and a high negative predictive value for the diagnosis of celiac disease. For example, a 2007 prospective study by Hadithi and colleagues included a total of 463 patients who were referred for evaluation of celiac disease (Hadithi, 2007). Sixteen (3.5%) of the 463 patients met ESPGHN diagnostic criteria for celiac disease, i.e., characteristic histologic findings (Marsh III) on small-bowel biopsy and unequivocal symptom resolution after initiating a gluten-free diet. All 16 patients were positive for HLA-DQ2 and/or HLA-DQ8. In contrast, 192 of 227 (43%) of patients who did not meet diagnostic criteria for celiac disease were positive for 1 or both of these alleles. Testing positive for HLA-DQ2 or HLA-DQ8 had a positive predictive value of 7.7% (95% confidence interval [CI]: 4.5-12%) and a negative predictive value of 100% (95% CI: 98.6-100%).
 
A study published in 2006 by Kapitany and colleagues included 70 patients who had been diagnosed with celiac disease 2 to 25 years prior using only results of small-bowel biopsy (Kapitany, 2006). Based on clinical follow-up, serologic testing and HLA-typing, as well as new biopsies in uncertain cases, evidence of celiac disease was found in 0 of the 15 patients who tested negative for both HLA-DQ2 and HLA-DQ8. Fourteen patients were found to be normal and 1 patient had insufficient data. A diagnosis of celiac disease was supported in 47 of 55 (85%) of patients who were positive for HLA-DQ2 and/or HLA-DQ8. Thirty-nine of the 47 patients (83%) were positive on anti-tissue transglutaminase (anti-TG) and/or EMA auto-antibody serological tests.
 
In 2012, Piccini and colleagues published findings of a case-control analysis that included 89 patients diagnosed with celiac disease and 70 healthy controls (Piccini, 2012). All of the patients with celiac disease and 64% of controls were positive for at least one of the HLA alleles known to be associated with the disease. The authors also tested 105 first-degree relatives of patients with celiac disease. Seventy-five percent of the family members were positive for one or more predisposing HLA alleles. Confirmatory biopsies were performed in relatives with celiac-associated HLA alleles and 8.6% of them (67% of all family members) were found to be affected by celiac disease.
 
Summary
Several studies have reported that the sensitivity and negative predictive value of HLA testing for celiac disease is 100%, meaning that this test is highly accurate for ruling out celiac disease. In contrast, a substantial number of patients who do not have celiac disease carry the HLA-DQ2 and/or HLA-DQ8 alleles, resulting in suboptimal specificity, meaning that this test is less accurate for confirming the diagnosis. National recommendations and study data support the conclusion that HLA typing is useful for ruling out celiac disease when patients have discordant serologic and histologic (biopsy) findings or when patients have persistent symptoms despite negative serology and histology. Thus, HLA typing may be considered medically necessary in these situations and is otherwise considered investigational.
 
Practice Guidelines and Position Statements
The National Institute for Health and Clinical Excellence (NICE): A 2009 guideline by this United Kingdom-based organization on celiac disease includes the following statement on HLA typing:
 
“Do not use human leukocyte antigen (HLA) DQ2/DQ8 testing in the initial diagnosis of coeliac disease. (However, its high negative predictive value may be of use to gastrointestinal specialists in specific clinical situations.” (NICE, 2013)
 
American Gastroenterological Association: In 2006, the American Gastroenterological Association issued a position statement on the diagnosis and management of celiac disease. Regarding serologic testing, they concluded that, in the primary care setting, the transglutaminase IgA antibody test is the most efficient single serologic test for diagnosing celiac disease. They state that the antiendomysial antibodies (EMA) IgA test is more time-consuming and operator dependent than the tTG. If IgA deficiency is strongly suspected, testing with IgG EMA and/or tTG IgG antibody test is recommended. If serologic test results are negative and celiac disease is still strongly suspected, providers can test for the presence of the disease-associated HLA alleles and, if present, perform small intestinal mucosal biopsy. Alternatively, if signs and symptoms suggest that small intestinal biopsy is appropriate, patients can proceed to biopsy without testing for HLA alleles (AGA, 2006).
National Institutes of Health (NIH): The NIH issued a Consensus Development Conference Statement in June 2004 bas
ed on a 2-day meeting and literature reviews by the University of Ottawa Evidence-based Practice Center. The NIH considered serologic testing as the first step in pursuing a diagnosis of celiac disease and stated that the best tests are the tTG IgA and EMA IgA tests, which they considered to be of equivalent accuracy. In individuals with suggestive symptoms and negative tTG IgA or EMA tests, consider an IgA deficiency and, if identified, it is recommended that a tTG IgG or EMA IgG be performed. When diagnosis is uncertain due to indeterminate test results, an option according to the NIH statement is to test for the genetic markers HLA-DQ2 or HLA-DQ8. Biopsy of the proximal small bowel is indicated in those with a positive celiac disease antibody test, except those with biopsy-proven dermatitis herpetiformis. No specific approach was suggested when there is positive serology and normal biopsy findings. Options include additional biopsies, repeat serology testing, and a trial of a gluten-free diet. Testing is indicated in individuals with gastrointestinal symptoms and other signs and symptoms suggestive of celiac disease (NH, 2004).
 
Of note, as of April 2013, there are no recommendations from the U.S. Preventive Services Task Force (USPSTF) related to screening for celiac disease in children or adults.
 
2014 Update
A literature search conducted through April 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHN): A 2012 guideline on the diagnosis of celiac disease stated that HLA-DQ2/ HLA-DQ8 testing should be offered to patients with an uncertain diagnosis of celiac disease eg, those with negative celiac disease-specific antibodies and mild infiltrate changes in small-bowel specimens. A negative finding renders celiac disease highly unlikely in these individuals (Husby, 2012).
 
2015 Update
A literature search conducted through May 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In 2014, Pallav and colleagues published a retrospective report of HLA testing in 256 patients with known or suspected CD (Pallay, 2014). Taking into account all available clinical and laboratory data, a total of 44 patients were diagnosed with CD and, in 173 patients CD was ruled out. A final diagnosis could not be obtained in 39 of 256 (15%) patients. HLA-DQ2 or DQ8 were absent in 40% of patients non-CD and 2 CD patients. The negative predictive value was 98%. A total of 154 patients were found to carry HLA-DQ2 or DQ8 alleles. Forty-two of the 44 patients diagnosed with CD tested positive for 1 or both of the above HLA alleles, with a test sensitivity of 95.5%. The diagnostic accuracy data are somewhat limited by the 15% of patients without a definitive diagnosis.
 
2018 Update
A literature search conducted using the MEDLINE database through May 2018 did not reveal any new information that would prompt a change in the coverage statement.
 
In 2017, Werkstetter et al reported on the results of a large, international prospective study to validate a biopsy free approach for diagnosis of CD in symptomatic children plus 10 times the upper limit of normal levels of immunoglobulin A against tissue transglutaminase (TGA-IgA) (aka serologic marker) and positive finding for HLA-DQ2 and -DQ8 (Werkstetter, 2017). The primary aim was to determine whether the nonbiopsy approach would identify children with CD with a PPV above 99% in clinical practice. Data on symptoms, total IgA, TGA, endomysium antibodies, and biopsy findings (reference standard) was collected from 803 consecutive pediatric patients (18 years) on a gluten-containing diet. When results were concordant, cases were classified as proven CD. Those with TGA-IgA levels of 3 times or below the upper limit of normal low but without other features of CD were classified no CD. Biopsy analyses were performed and reviewed in a blinded manner. Inconclusive cases were regarded as not having CD. Data were analyzed for 707 children (65.1% girls; median age, 6.2 years) 645 were diagnosed with CD, 46 were found not to have CD, and 16 had inconclusive results. Use of test results including TGA-IgA 10 times or more the upper limit of normal, a positive result from the test for endomysium antibodies, and any symptom identified children with CD (n=399) yielded a PPV of 99.75% (95% CI, 98.61% to 99.99%); the PPV was 100% (95% CI, 98.68% to 100%) when only malabsorption symptoms were used instead of any symptom (n=278). The inclusion of HLA analyses did not increase accuracy.
 
A 2016 report by Agency of Healthcare Research and Quality indicated that HLA testing could be used to rule out CD with close to 100% sensitivity (Maglione, 2016). The report cited the 2013 American College of Gastroenterology estimates11 of NPV of the HLA-DQ2 and -DQ8 combination test at over 99%. In the Agency report, 2 studies were cited on the accuracy of HLA testing, a large 2013 prospective cohort found that HLA testing had a sensitivity of 100% and specificity of 18.2%and a 1999 cohort also reported a sensitivity of 100% and a specificity of 33.3%.
 
2019 Update
A literature search was conducted through May 2019.  There was no new information identified that would prompt a change in the coverage statement.  
 
2020 Update
A literature search was conducted through May 2020.  There was no new information identified that would prompt a change in the coverage statement.  
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In 2019, the clinical practice update on diagnosis and management of celiac disease (CD) from the American College of Gastroenterology stated the following on human leukocyte antigen (HLA) gene testing:
"Determination of HLA-DQ2/DQ8 has a limited role in the diagnosis of CD. Its value is largely related to its negative predictive value to rule out CD in patients who are seronegative in the face of histologic changes, in patients who did not have serologic confirmation at the time of diagnosis, and in those patients with a historic diagnosis of celiac disease; especially as very young children prior to the introduction of celiac-specific serology (Husby, 2019)."
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In 2021, the American Gastroenterological Association (AGA) Institute released a clinical practice update on the evaluation and management of patients with suspected enteropathy, but negative serologic test results for CD and included the following statement on HLA genetic testing:
 
"In cases of suspected seronegative CeD [celiac disease], genetic testing should be performed to determine whether the patient carries an HLA genotype (DQ2 or DQ8) that is compatible with developing CeD...HLA genetic testing is most helpful for patients if results are negative, as this excludes the possibility of seronegative CeD as a diagnosis. However, compatible genetics infer that the patient has a risk of developing CeD, but these results cannot stand alone as a diagnostic criterion." (Leonard, 2021)
 
These guidelines also recommend that a gastroenterologist or CD specialist review and evaluated all reported and tested alleles before determining that a patient is HLA-negative.
 
In 2016, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, in conjunction with the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition, released a clinical report on the diagnosis and treatment of gluten-related disorders. Regarding HLA tests, the authors stated that HLA testing should not be used as an initial test used for diagnosis of CD (Hill, 2016). This testing should be reserved for patients where discrepancies are found between their serological and histologic findings, or when patients have commenced a gluten-free diet prior to any testing. In these patients, if neither HLA-DQ2 nor DQ8 is found upon testing, the diagnosis of CD is unlikely.
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2023. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Oliveira et al evaluated serologic tests as markers of CD in a retrospective cohort study in 94 children with type 1 diabetes mellitus who underwent screening for CD. Type 1 diabetes mellitus confers high risk for CD and baseline propensity for HLA-DQ2 or -DQ8 positivity was assessed (Oliveira, 2022). Data for HLA testing were missing in 42 patients. Among the 52 patients with available results, 44 (84.6%) were positive for HLA-DQ2 or -DQ8. Four (4.3%) patients screened positive for CD by IgA or IgG antibodies against TGA or endomysium, all of whom underwent biopsy and had histology consistent with CD. Of these 4 patients diagnosed with CD, 3 had undergone HLA testing, all of whom were positive for HLA-DQ2 or -DQ8, corresponding to 100% sensitivity and NPV. Specificity and PPV of HLA testing for CD were 16.6% and 9.1%, respectively.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
The American College of Gastroenterology guideline for diagnosis and management of celiac disease was updated in 2023; the recommended diagnostic approach did not change since the 2013 guideline (Rubio-Tapia, 2023).

CPT/HCPCS:
81377HLA Class II typing, low resolution (eg, antigen equivalents); one antigen equivalent, each
81382HLA Class II typing, high resolution (ie, alleles or allele groups); one locus (eg, HLA DRB1, DRB3/4/5, DQB1, DQA1, DPB1, or DPA1), each
81383HLA Class II typing, high resolution (ie, alleles or allele groups); one allele or allele group (eg, HLA DQB1*06:02P), each

References: AGA Institute.(2006) Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology 2006; 131(6):1977-80.

Basso MS, Luciano R, Ferrettio F, et al.(2012) Association between celiac disease and primary lactase deficiency. European Journal of Clinical Nutrition. 2012:66; 1364-1365.

Bodlaj G, Stocher M, Hufnagl P, et al.(2006) Genotyping of the lactase-phlorizin hydrolase-13910 polymorphism by LightCycler PCR and implications for the diagnosis of lactose intolerance. Clin Chem. 2006; 52(1):148-51.

Bulhoes AC, Goldani HA, Oliveira FS, et al.(2013) Correlation between lactose absorption and the C/T-13910 and G/A-22018 mutations of the lactase-phlorizin hydrolase (LCT) gene in adult-type hypolactasia. Gene Nutr. 2013 Jan;8(1):145-51.

Green P. and Cellier C.(2007) Celiac Disease. N Engl J Med. 2007; 357:1731-43.

Haberkorn BC, Ermens AA, Koeken A, et al.(2011) Improving diagnosis of adult-type hypolactasia in patients with abdominal complaints. Clin Chem Lab Med. 2011 Sep 21;50(1):119-23.

Hadithi M, Pena AS.(2010) Current methods to diagnose the unresponsive and complicated forms of coeliac disease. Eur J Intern Med 2010; 21(4):247-53.

Hadithi M, von Blomberg BM, Crusius JB et al.(2007) Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. Ann Intern Med 2007; 147(5):294-302.

Hill ID, Dirks MH, Liptak GS et al.(2005) Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2005; 40(1):1-19.

Hill ID, Fasano A, Guandalini S, et al.(2016) NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related Disorders. J Pediatr Gastroenterol Nutr. Jul 2016; 63(1): 156-65. PMID 27035374

Husby S, Koletzko S, Korponay-Szabo IR et al.(2012) European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54(1):136-60.

Husby S, Murray JA, Katzka DA.(2019) AGA Clinical Practice Update on Diagnosis and Monitoring of Celiac Disease-Changing Utility of Serology and Histologic Measures: Expert Review. Gastroenterology. Mar 2019; 156(4): 885-889. PMID 30578783

Kapitany A, Toth L, Tumpek J et al.(2006) Diagnostic significance of HLA-DQ typing in patients with previous coeliac disease diagnosis based on histology alone. Aliment Pharmacol Ther 2006; 24(9):1395-402.

Laaksonen MM, Mikkila V, Rasanen L, et al.(2009) Genetic lactase non-persistence, consumption of milk products and intakes of milk nutrients in Finns from childhood to young adulthood. Br J Nutr. 2009 Jul;102(1):8-17.

Leonard MM, Lebwohl B, Rubio-Tapia A, et al.(2021) AGA Clinical Practice Update on the Evaluation and Management of Seronegative Enteropathies: Expert Review. Gastroenterology. Jan 2021; 160(1): 437-444. PMID 33010252

Maglione MA, Okunogbe A, Ewing B, et al.(2016) Diagnosis of Celiac Disease (Comparative Effectiveness Review No. 162). Rockville (MD): Agency for Healthcare Research and Quality; 2016.

Marton A, Xue X, Szilagyi A.(2012) Meta-analysis: the diagnostic accuracy of lactose breath hydrogen or lactose tolerance tests for predicting the North European lactase polymorphism C/T-13910. Aliment Pharmacol Ther. 2012 Feb;35(4):429-40.

Megiorni F, Pizzuti A.(2012) HLA-DQA1 and HLA-DQB1 in Celiac disease predisposition: practical implications of the HLA molecular typing. J Biomed Sci 2012; 19:88.

Mendoza Torres E, Varela Prieto LL, Villarreal Camacho JL, Villanueva Torregroza Da.(2012) Diagnosis of adult-type hypolactasia/lactase persistence: genotyping of single nucleotide polymorphism (SNP C/T-13910) is not consistent with breath test in Colombian Caribbean population. Arq Gastroenterol. 2012 Jan-Mar;49(1):5-8.

National Institute for Health and Care Excellence (NICE).(2013) NICE clinical guideline 86: Recognition and assessment of coeliac disease. Available online at: www.nice.org.uk/cg86. Last accessed April, 2013.

National Institute of Diabetes and Digestive and Kidney Diseases.(2020) Definition & Facts for Celiac disease. Reviewed October 2020. Accessed September 23, 2022.

NIH consensus development conference on celiac disease. Consensus development conference statement. 2004. Available online at: http://consensus.nih.gov/2004/2004celiacdisease118html.htm. Last accessed April, 2013.

Oliveira DR, Rebelo JF, Maximiano C, et al.(2022) HLA DQ2/DQ8 haplotypes and anti-transglutaminase antibodies as celiac disease markers in a pediatric population with type 1 diabetes mellitus. Arch Endocrinol Metab. Apr 28 2022; 66(2): 229-236. PMID 35420265

Pallav K, Kabbani T, Tariq S, et al.(2014) Clinical utility of celiac disease-associated HLA testing. Dig Dis Sci. Sep 2014;59(9):2199-2206. PMID 24705698

Piccini B, Vascotto M, Serracca L et al.(2012) HLA-DQ typing in the diagnostic algorithm of celiac disease. Rev Esp Enferm Dig 2012; 104(5):248-54.

Suchy FJ, Brannon PM, Carpenter TO, et al.(2010) NIH consensus development conference statement on lactose intolerance and health. NIH Consens State Sci Statements 2010 Feb 22-24;27(2):1-27.

Walker-Smith JA GS, Schmitz J, et al.(1990) Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child 1990; 65(8):909-11.

Werkstetter KJ, Korponay-Szabo IR, Popp A, et al.(2017) Accuracy in diagnosis of celiac disease without biopsies in clinical practice. Gastroenterology. Oct 2017;153(4):924-935. PMID 28624578


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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