Celiac disease laboratory tests
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: : Iqra Qamar M.D.[2]
Overview
Laboratory Findings
Electrolyte and Biomarker Studies
- Complete blood count (CBC)
- Liver function tests (LFTs)
- B12
- Vitamin D
- Folate
- Ferritin (+/- Ca, alk phos) – at diagnosis and annually
Serologic Markers
Serologic tests may be divided into 2 groups based upon antibodies against respective antigens:
- anti-TTG Ab tests
- anti-gliadin antibody tests
IgA endomysial antibody (IgA EMA):
- Endomysial antibodies bind to the endomysium and can be seen via indirect immunofluorescence producing a staining pattern. The target antigen is a tissue transglutaminase
- IgA EMA have high specificity and even low titres indicate a positive test result
- It has moderate sensitivity but high specificity for untreated celiac disease and is negative in treated patients.
IgA tissue transglutaminase antibody (IgA tTG):
- These antibodies are directed against tissue transglutaminase-2 (tTG) antigen.[1]
- They can be easily detected by ELISA[2]
- Anti-tTG antibodies have high diagnostic accuracy[3][4][5][6][7]
IgG tissue transglutaminase antibody (IgG tTG)
IgA deamidated gliadin peptide (IgA DGP)
IgG deamidated gliadin peptide (IgG DGP)
NOTE:
- Serum IgA EMA and IgA tTG have the highest diagnostic accuracy
- The IgA and IgG antigliadin antibody (AGA) are not recommended for estabilishing diagnosis as they have low accuracy and give more false positive results when compared with IgA tTG and IgA DGP assays
- The anti-deamidated gliadin peptide (DGP) assays also have high diagnostic accuracy
Sensitivity and Specificity of Antibody testing:
Literature review has shown that IgA endomysial and IgA tissue transglutaminase antibodies have a sensitivity more than 95% and a specificity almost 100%. However variations in results are seen among different laboratories.[8][9][10][11][12][13][14]
Test | sensitivity | specificity |
---|---|---|
IgA enomysial antibody | 85 to 98% | 97 to 100% |
IgA tissue transglutaminase antibody | 90 to 98% | 95 to 97% |
IgA deamidated gliadin peptide | 94% | 99% |
IgG deamidated gliadin peptide | 92% | 100% |
Test | sensitivity | specificity |
---|---|---|
HLA-DQ2 | 94% | 73% |
HLA-DQ8 | 12% | 81% |
Abbreviations:DGP: deamidated gliadin peptide; HLA: human leukocyte antigen; Ig: immunoglobulin; TTGA: tissue transglutaminase antibody.
Low Probability (<5%) | |||||||||||||||||||||||||||||||||||||||
TTGA IgA ± IgA level | |||||||||||||||||||||||||||||||||||||||
Positive TTGA | Negative TTGA ↓ IgA | Negative TTGA Normal IgA | |||||||||||||||||||||||||||||||||||||
TTGA IgG ± DGP IgG | |||||||||||||||||||||||||||||||||||||||
If any positive | All negative | ||||||||||||||||||||||||||||||||||||||
Biopsy | Celiac disease unlikely | ||||||||||||||||||||||||||||||||||||||
High probability (>5%) | |||||||||||||||||||||||||||||||
• Duodenal biopsy • TTGA IgG | |||||||||||||||||||||||||||||||
Both negative | Both positive | Serology/biopsy disagreement | |||||||||||||||||||||||||||||
Celiac disease unlikely | Celiac disease | Needs • HLA DQ2 and DQ8 genotyping •IgA level ± TTGA/DGP IgG •work up for other causes of villous atrophy | |||||||||||||||||||||||||||||
References
- ↑ Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D (1997). "Identification of tissue transglutaminase as the autoantigen of celiac disease". Nat. Med. 3 (7): 797–801. PMID 9212111.
- ↑ Tonutti E, Visentini D, Bizzaro N, Caradonna M, Cerni L, Villalta D, Tozzoli R (2003). "The role of antitissue transglutaminase assay for the diagnosis and monitoring of coeliac disease: a French-Italian multicentre study". J. Clin. Pathol. 56 (5): 389–93. PMC 1769943. PMID 12719462.
- ↑ Dieterich W, Laag E, Schöpper H, Volta U, Ferguson A, Gillett H, Riecken EO, Schuppan D (1998). "Autoantibodies to tissue transglutaminase as predictors of celiac disease". Gastroenterology. 115 (6): 1317–21. PMID 9834256.
- ↑ Sulkanen S, Halttunen T, Laurila K, Kolho KL, Korponay-Szabó IR, Sarnesto A, Savilahti E, Collin P, Mäki M (1998). "Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease". Gastroenterology. 115 (6): 1322–8. PMID 9834257.
- ↑ Troncone R, Maurano F, Rossi M, Micillo M, Greco L, Auricchio R, Salerno G, Salvatore F, Sacchetti L (1999). "IgA antibodies to tissue transglutaminase: An effective diagnostic test for celiac disease". J. Pediatr. 134 (2): 166–71. PMID 9931524.
- ↑ Hopper AD, Cross SS, Hurlstone DP, McAlindon ME, Lobo AJ, Hadjivassiliou M, Sloan ME, Dixon S, Sanders DS (2007). "Pre-endoscopy serological testing for coeliac disease: evaluation of a clinical decision tool". BMJ. 334 (7596): 729. doi:10.1136/bmj.39133.668681.BE. PMC 1847864. PMID 17383983.
- ↑ Hopper AD, Hadjivassiliou M, Hurlstone DP, Lobo AJ, McAlindon ME, Egner W, Wild G, Sanders DS (2008). "What is the role of serologic testing in celiac disease? A prospective, biopsy-confirmed study with economic analysis". Clin. Gastroenterol. Hepatol. 6 (3): 314–20. doi:10.1016/j.cgh.2007.12.008. PMID 18328437.
- ↑ Mäki M (1995). "The humoral immune system in coeliac disease". Baillieres Clin. Gastroenterol. 9 (2): 231–49. PMID 7549026.
- ↑ Abrams JA, Brar P, Diamond B, Rotterdam H, Green PH (2006). "Utility in clinical practice of immunoglobulin a anti-tissue transglutaminase antibody for the diagnosis of celiac disease". Clin. Gastroenterol. Hepatol. 4 (6): 726–30. doi:10.1016/j.cgh.2006.02.010. PMID 16630760.
- ↑ Swallow K, Wild G, Sargur R, Sanders DS, Aziz I, Hopper AD, Egner W (2013). "Quality not quantity for transglutaminase antibody 2: the performance of an endomysial and tissue transglutaminase test in screening coeliac disease remains stable over time". Clin. Exp. Immunol. 171 (1): 100–6. doi:10.1111/cei.12000. PMC 3530101. PMID 23199329.
- ↑ Sugai E, Vázquez H, Nachman F, Moreno ML, Mazure R, Smecuol E, Niveloni S, Cabanne A, Kogan Z, Gómez JC, Mauriño E, Bai JC (2006). "Accuracy of testing for antibodies to synthetic gliadin-related peptides in celiac disease". Clin. Gastroenterol. Hepatol. 4 (9): 1112–7. doi:10.1016/j.cgh.2006.05.004. PMID 16860613.
- ↑ Prince HE (2006). "Evaluation of the INOVA diagnostics enzyme-linked immunosorbent assay kits for measuring serum immunoglobulin G (IgG) and IgA to deamidated gliadin peptides". Clin. Vaccine Immunol. 13 (1): 150–1. doi:10.1128/CVI.13.1.150-151.2006. PMC 1356631. PMID 16426013.
- ↑ Kelly CP, Feighery CF, Gallagher RB, Gibney MJ, Weir DG (1991). "Mucosal and systemic IgA anti-gliadin antibody in celiac disease. Contrasting patterns of response in serum, saliva, and intestinal secretions". Dig. Dis. Sci. 36 (6): 743–51. PMID 2032515.
- ↑ Rostami K, Kerckhaert J, Tiemessen R, von Blomberg BM, Meijer JW, Mulder CJ (1999). "Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice". Am. J. Gastroenterol. 94 (4): 888–94. doi:10.1111/j.1572-0241.1999.983_f.x. PMID 10201452.