Clinical settings in which human leukocyte antigen typing is still useful in the diagnosis of celiac disease

Table 3 Clinical settings where it is reasonable to propose human leukocyte antigen genotyping for celiac disease

Condition	HLA-DQ2 and HLA-DQ8 negativity
Before biopsy
First-degree relatives of a patient affected by CD	Allows the exclusion of serological monitoring in individuals not carrying any genetic risk
Individuals who have started a GFD without performing t-TG2-IgA measurement	Allows the exclusion of CD as the cause of gastrointestinal symptoms regardless of the clinical response to the GFD
Individuals with persistent low t-TG2-IgA titer	Allows unequivocal definition of the false positives, including first-degree relatives of a proband with reduced gluten intake
Individuals affected by IgA deficiency	Allows the exclusion of serological monitoring in individuals not carrying any HLA genetic risk
Patients with chromosomal pathologies associated with increased CD risk (Down syndrome, Turner syndrome, Williams syndrome)	Allows the limit of periodic serological follow-up exclusively to positive patients
Patients affected by Hashimoto’s thyroiditis	Allows the limit of the periodic serological follow-up exclusively to positive patients
After biopsy
Ineffectiveness of GFD in patients with CD	Allows exclusion of CD and suspect other pathologies. Could help in excluding refractory CD type II and enteropathy-associated T cell lymphoma
Dubious CD biopsy performed for other reasons	Allows exclusion of CD and suspect other pathologies

GFD: Gluten free diet; HLA: Human leukocyte antigens; CD: Celiac disease; t-TG2-IgA: Tissue transglutaminase type 2-IgA.