Human Leukocyte Antigen DQ2.2 and Celiac Disease

Abstract

Patients with celiac disease (CD) lacking both human leukocyte antigen (HLA)-DQ2.5 in cis (DQA1*05:01, DQB1*02:01) or trans (DQA1*05:05, DQB1*02:02) configuration and HLA-DQ8 (DQA1*03:01, DQB1*03:02) are considered to be rare. Therefore, absence of these genotypes is commonly used to exclude the diagnosis of CD. To investigate whether this approach is justified, the HLA-distribution in 155 children with CD was studied. A total of 139 (89.7%) patients carried HLA-DQ2.5. Of the remaining patients, 7 (4.5%) carried HLA-DQ8. Interestingly, the 9 (5.8%) patients lacking HLA-DQ2.5 and HLA-DQ8 carried HLA-DQA1*02:01 and -DQB1*02:02 (HLA-DQ2.2). Therefore, HLA-DQ2.2 should be included as an important HLA-type related to CD.

Prevalence of Celiac Disease Predisposing Genotypes, Including HLA-DQ2.2 Variant, in Brazilian Children

“…Previous studies already showed that a great proportion of DQ2.5 and DQ8 negative CD patients were positives for the DQ2.2 variant (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) concluding that DQ2.2 should be considered as a risk variant for celiac disease. Other studies also gave details on the probable molecular role of the heterodimer coded by this variants (18,19) .…”

“…However, due to their heterogeneous distribution in different populations around the world, genotypes' prevalence must be first characterized for the local population to be able to compare it to at-risk subjects. The inclusion of HLA-DQ2.2 as a predisposing variant for celiac disease remains under discussion with it being significant for some but not all studied populations (6)(7)(8)(9)(10)(11)(12)(13) . Although about 30%-40% of the general population carry HLA-DQ2 and/or DQ8 without developing CD, these alleles are absent in less than 0.5% of CD patients (14) .…”

“…Although about 30%-40% of the general population carry HLA-DQ2 and/or DQ8 without developing CD, these alleles are absent in less than 0.5% of CD patients (14) . HLA typing is considered an excellent tool to be used before performing more invasive tests like endoscopy, when serology is ambiguous in subjects being investigated for CD (4)(5)(6)(7)(8) . Additionally, in individuals considered at high risk for CD as first-degree relatives, patients with immunoglobulin A deficiency, other autoimmune diseases or with Down, Turner or Williams syndromes, the HLA typing is used to exclude those in which these alleles are absent from further investigation.…”

“…However, there are still some patients that don´t carry neither of these predisposing variants. In an attempt to describe the genetic bases of the disease on those patients, some authors found significance in the association between celiac disease and HLA-DQ2.2 (DQA1*02:01 -DQB1*02:02) (6) but they are still a lot of controversies regarding the role of this heterodimer.…”

Present View of the Management and Tasks in the Celiac Disease Field: From Diagnosis to Therapy

“…Discussions are still held among the choice of forms of screening with the best combination, including good specificity, sensitivity and lower cost of a shorter period of time from receipt of materials, through processing to delivery of the actual outcome. Elsewhere, there is a support for the implementation of some special genetic test [11]. Other authors recommend that each endoscopy biopsy sampling implement should contain several samples of small intestine with special needs in functional dyspepsia, or even regardless of the cause of examination [9,15].…”