Common immunogenetic profile in children with multiple autoimmune diseases: the signature of HLA-DQ pleiotropic genes

Abstract

Type 1 diabetes mellitus (T1DM), celiac disease (CD) and autoimmune thyroid disease (ATD) are autoimmune conditions relatively common in paediatric age and frequently occur in association in the same subject. This event is not by chance and requires an explanation. Here, we studied the distribution of HLA-DQ αβ heterodimers in 334 Italian children with T1DM, ATD and CD alone or in association and in 224 Italian healthy controls. In particular, 164 patients had T1DM (133 alone, 20+ATD, 7+CD and 4+CD+ATD), 118 had ATD (110 alone, 8+CD) and 52 had CD (40 alone, 11+ATD and 1+T1DM). 51 patients suffered from multiple autoimmune diseases. The risk for multiple autoimmune diseases was significantly associated with the increased number of HLA-DQ markers of susceptibility for both T1DM (p = 0.003) and CD (p = 0.006). The presence of one or more diabetogenic DQ molecules significantly increased the probability of developing not only T1DM (p < 0.001) but also CD (p < 0.001) and ATD (p = 0.001). Similarly, the presence of one or more celiac HLA-DQ heterodimers significantly increased the likelihood of developing not only CD (p < 0.001), but also T1DM (p < 0.001) and ATD (p < 0.001). We confirm that the sharing of the immunogenetic background is responsible for the development of multiple autoimmune diseases although with a different risk according to the number and type of susceptible HLA-DQ heterodimers as reported in the algorithm proposed here. It is likely that combinations of DQA1 and DQB1 alleles are the real culprits of the progression towards multiple autoimmune diseases and HLA-DQ genomic typing will improve the capability to predict associated autoimmune diseases in infancy.

Keywords::

• HLA-DQ
• autoimmune disease
• children
• multiple

Acknowledgements

This work was financially supported by current researches 594, 556 and 657 of IRCCS Foundation Policlinico San Matteo (Pavia, Italy) dedicated to ameliorate the quality of the local reservoir of adult stem cell donors extending the typing of volunteers to HLA-DQA1 and DQB1 genes.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Notice of CorrectionThe version of this article published online ahead of print on 11 July 2012 contained an error in Table I on page 3. In table 1a, the numbers “15 (28.85%)” should have read “25 (28.85%)”. In table 1b, the numbers “41 (34.75%)” should have read “16 (13.56%)”. These errors has been corrected for this version.