Reducing the Need for Intestinal Biopsy in Suspected Celiac Patients

Celiac disease (CD) is a digestive condition caused by an adverse, autoimmune reaction to gluten. Symptoms include diarrhoea, bloating, weight loss, abdominal pain, malnutrition and failure to thrive in children.

The current gold standard test for CD diagnosis is intestinal biopsy; however, given the invasive nature of biopsies and the cost of the procedure, laboratory screening tests are used to identify individuals with a high-probability of having the disease.

Gliadin, tissue transglutaminase and endomysial antibodies are markers of CD. Traditionally, assaying for anti-endomysial antibodies (EMA) was the classic laboratory screening test; however, laboratories are increasingly looking to use automated assays for celiac disease testing.

Sonia Nicholas, SelectScience's Clinical Editor, spoke to Dr Robert Reinhardt, Medical Director for Thermo Fisher Scientific, about the modern approach to Celiac screening.

SN: Dr Reinhardt, what are the disadvantages of the celiac screening assays currently available?
RR: EMA has excellent diagnostic accuracy; however, it is labor intensive. EMA also requires the use of a fluorescent microscope, and a skilled technician. Laboratories are looking for faster, more efficient assays that can be run by a larger pool of laboratory staff. Anti-tissue Transglutaminase Antibody (tTG) assays are now routinely used to test patients for CD. But even with this one assay, the use of different antigens by different manufacturers has significant influence on assay performance; this means that there can be considerable difference in sensitivity and specificity between the different assays commercially available. In addition, both the EMA and tTG are less sensitive in young pediatric patients (1).

SN: What assays do you supply for the assessment of patients suspected of having CD?
RR: Thermo Fisher Scientific supplies the ELiA^TM Celikey^TM assay for the quantitative determination of IgA or IgG antibodies to tTG, as well as the EliA^TM Gliadin Assays for the assessment of IgA or IgG antibodies to Gliadin and Deamidated Peptide.

SN: Can you tell me more about the recombinant tTG antigen that is used in your assays?
RR: Our Celikey assays use a human recombinant tTG IgA and IgG expressed in the baculovirus/insect cell system. The advantage of using this recombinant tTG is that is has a very high specificity and sensitivity compared to other assays. The use of recombinant tTG also ensures that our customers have consistency in the antigen from lot to lot and no risk of contaminating human proteins.

SN: What is the current recommendation for the laboratory diagnosis of celiac disease?
RR: Studies have shown that a combination of three or four antibody tests, including either the IgA anti-tTG and/or IgA anti-endomysium, may allow for the diagnosis, or exclusion, of celiac disease without the need for biopsy (2). Research also shows that in very young children, anti-tTG IgA combined with anti-deaminated gliadin peptides IgG is the best test combination for the diagnosis of CD (1). The Celikey assay solutions provided by Thermo Fisher Scientific enable laboratories to carry out these test combinations simultaneously on a single patient specimen.

SN:What are the advantages to the patient when laboratories use the Celikey assays?
RR: Use of these assays offers improved early detection of celiac disease, allowing for the reduction of unnecessary biopsies and treatments, improving patient outcomes. European guidelines now let the clinician make the diagnosis based on very high (>100) anti-tTG results, obviating the need for biopsy.

SN: Are your assays available in all countries? On which analyzers can the assays be run?
RR: Yes all of our assays are globally available now. The assays can be run on the Phadia 100, Phadia 250, and soon on the Phadia 2500 and Phadia 5000.

References:
1. Ignazio Brusca1,*, Antonio Carroccio2, Elio Tonutti3, Danilo Villalta4, Renato Tozzoli5, Maria Barrale1, Filippo M. Sarullo1, Pasquale Mansueto6, Stella Maria La Chiusa1, Giuseppe Iacono7 and Nicola Bizzaro8. The old and new tests for celiac disease: which is the best test combination to diagnose celiac disease in pediatric patients? Clin Chem Lab Med. 2012;50(1):111–117 _ 2011.

2. Annemarie Bürgin-Wolff1, Buser Mauro2 and Hadziselimovic Faruk1* Bürgin-Wolff et al. Intestinal biopsy is not always required to diagnose celiac disease: a retrospective analysis of combined antibody tests. BMC Gastroenterology 2013, 13:19 http://www.biomedcentral.com/1471-230X/13/19

Image Caption: Robert Reinhardt MD is US Medical Director, ImmunoDiagnostics, ThermoFisher Scientific, and Associate Professor of Family Medicine at the Michigan State University College of Human Medicine. ImmunoCAP® specific and total IgE (allergy) blood testing technology is the acknowledged global leader, both scientifically and commercially. Dr Reinhardt has previously been on the medical school faculties at the University of Michigan and at Brown University, where he also completed his residency.