Riassunto
Premesse
. La malattia celiaca (MC) è una condizione clinica multifattoriale scatenata da un fattore esterno, il glutine, su una base genetica predisponente, dove il ruolo principale è svolto dai geni DQ2 e/o DQ8 appartenenti al sistema Human Leucocyte Antigen (HLA) di classe II. Nelle malattie complesse i test genetici sono predittivi di suscettibilità, ma non risultano avere un significativo ruolo diagnostico. Al contrario, nella MC la tipizzazione HLA può essere di notevole aiuto, come per esempio nei casi di malattia celiaca refrattaria o in soggetti a rischio, quali i familiari di primo grado del paziente celiaco.
La tipizzazione dell’HLA presenta alcuni limiti, dovuti principalmente al suo elevato costo e alla difficoltà di esecuzione del test. In questo studio sono state valutate le performance di due test: il Celiac Gene Screen e il Celiac Gene Typing, proposti da BioDiagene (Palermo, Italia). I due test sono stati comparati con il test per HLA DQ2/DQ8 della Eurospital (Trieste, Italia).
Metodi
. Lo studio è stato eseguito su 95 pazienti, di cui 7 con diagnosi di MC. Il Celiac Gene Screen è un test genetico rapido e a basso costo che permette di definire se nel campione in esame è presente uno degli alleli DQ2 o DQ8 indipendentemente dallo stato di omozigosi o eterozigosi. Il secondo metodo è invece in grado di determinare nello specifico il genotipo HLA, permettendo la stratificazione del rischio genetico per MC.
Risultati
. È stata ottenuta una concordanza del 100% sia fra i due test BioDiagene sia rispetto al test Eurospital.
Conclusioni
. Questo studio ha evidenziato le ottime performance dei due metodi. Inoltre, l’utilizzo del Celiac Gene Screen, grazie al suo basso costo, potrebbe modificare l’algoritmo diagnostico di laboratorio finora proposto e costituire esso stesso un test di primo livello, almeno in soggetti asintomatici, ma con elevate condizioni di rischio per lo sviluppo della MC e, ancora, rappresentare un test di screening di popolazione.
Summary
Background
. Celiac disease (CD) is a multifactorial disorder characterized by intolerance to gluten and associated to genetic predisposition, mainly with Human Leucocyte Antigens (HLA) class II genes. In the complex pathologies, genetic tests are predictive of susceptibility, but they aren’t diagnostic. However, its determination can be helpful in several cases, for example, refractory celiac disease or in risk groups, as first-degree relatives of patients with celiac disease.
Typing HLA pattern have several limits: elevated cost, execution time too long, difficult interpretation of results. Moreover, genetic tests are limited to specialized laboratories.
In this study we have assessed the performance of two tests: the Celiac Gene Screen and the Celiac Gene Typing (BioDiagene, Palermo, Italy). The two tests are compared with the Eu-Gen Risk Eurospital kit (Trieste, Italy).
Methods
. We have analyzed 95 subjects, 7 of these presented CD. The Celiac Gene Screen is a test for identification of samples susceptible to CD, but it does not discriminate the DQ2 and DQ8 alleles, independently homozygosis or heterozygosis status.
The Celiac Gene Typing is a method for the detection of HLA class II genotype associated with CD. For each sample analyzed, individual alleles are detected by the kit and the corresponding serologic haplotype. Celiac Gene Typing identifies the presence of the alleles that codify for the DQ2 and DQ8 heterodimers that determine the risk of developing CD.
Results
. We have obtained 100% concordance between two BioDiagene tests and Eurospital test.
Conclusions
. This study has underlined excellent performances of two methods. Furthermore, the use of Celiac Gene Screen, to low cost, could be modify diagnostic laboratory flow-chart proposed until now, and it become a test of first level, at least in asymptomatic subjects, but with elevated risk conditions to develop the CD and, even, represent a screening test of population.
This is a preview of subscription content, log in via an institution to check access.
Bibliografia
Mustalahti K, Catassi C, Reunanen A (2010) The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann Med 42:587–595
Catassi C, Kryszac D, Bhatti B et al. (2010) Natural history of celiac disease autoimmunity in a USA cohort followed since 1974. Ann Med 42:530–538
Catassi C, Ratsch IM, Fabiani E et al. (1994) Coeliac disease in the year 2000: exploring the iceberg. Lancet 343:200–203
Fernandez A, Gonzalez L, de la Fuente J (2010) Coeliac disease: clinical features in adult populations. Rev Esp Enferm Dig 102:466–471
Gasbarrini G, Ciccocioppo R, De Vitis I et al. (2001) Coeliac disease in the elderly. A multicentre Italian study. Gerontology 47:306–310
Fasano A, Catassi C (2001) Current approaches to diagnosis and treatment on celiac disease: an evolving spectrum. Gastroenterology 120:636–651
Tosco A, Salviati VM, Auricchio R (2011) Natural history of potential celiac disease in children. Clin Gastroenterol Hepatol 9:320–325
Freeman HJ, Chopra A, Clandinin MT et al. (2011) Recent advances in celiac disease. World J Gastroenterol 17:2259–2272
Maglio M, Florian F, Vecchio M et al. (2009) Majority of children with type 1 diabetes produce and deposit anti-tissue transglutaminase antibodies in the small intestine. Diabetes 58:1578–1584
Ventura A, Magazzù G, Greco L (1999) Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. Gastroenterology 117:297–303
Pan SY, Morrison H (2011) Epidemiology of cancer of the small intestine. World J Gastrointest Oncol 3:33–42
Richir M, Songun I, Wientjes C et al. (2010) Small bowel adenocarcinoma in a patient with coeliac disease: case report and review of the literature. Case Rep Gastroenterol 4:416–420
Al-Toma A, Goerres MS, Meijer JW et al. (2006) Human leukocytes antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma. Clin Gastroenterol Hepatol 4:315–319
Mascart-Lemone F, Lambrechts A (1995) Serology of coeliac disease: early diagnosis and therapeutic impact. Acta Gastroenterol Belg 58:388–396
Hugh H, Fudenberg JRL, An-Chuan W et al. (1984) Basic immunogenetics, 3rd edn. Oxford University Press, London
Roitt M, Brostoff J, Male DK (1998) T-cell receptors and major histocompatibility complex molecules. Immunology. 5th edn. Churchill Livingston, London
Ferrer A, Fernandez ME, Nazabal M (2005) Overview on HLA and DNA typing methods. Biotecnologia Appl 22:91–101
Bourgey M, Calcagno G, Tinto N et al. (2007) HLA related genetic risk for coeliac disease. Gut 6:1054–1059
Murray JA, Moore SB, Van Dyke CT et al. (2007) HLA DQ gene dosage and risk and severity of celiac disease. Clin Gastroenterol Hepatol 5:1406–1412
Tonutti E, Visentini D, Bizzaro N et al. (2005) Linee guida per la diagnosi di laboratorio e istologica della malattia celiaca. RIMeL/IJLaM 1:110–122
Megiorni F, Mora B, Bonamico M et al. (2008) A rapid and sensitive method to detect specific human lymphocyte antigen (HLA) class II alleles associated with celiac disease. Clin Chem Lab Med 46:193–196
Husby S, Koletzko S, Korponay-Szabò IR et al. (2012) European Society for pediatric gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 54:136–160
Conflitto di interesse
Nessuno.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Terzuoli, L., Porcelli, B., Trevisan, M.T. et al. Valutazione di un nuovo metodo per la tipizzazione HLA nella malattia celiaca. Riv Ital Med Lab 9, 149–154 (2013). https://doi.org/10.1007/s13631-013-0016-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13631-013-0016-0