Concordance of Dermatitis Herpetiformis and Celiac Disease in Monozygous Twins

Abstract

Celiac disease can be defined as the classical manifestation of gluten sensitivity, which primarily affects the small intestine. Gluten sensitivity has also a skin manifestation, i.e., dermatitis herpetiformis. Both diseases have a strong genetic association with HLA DQ on chromosome 6. In this study we tried to estimate how much different clinical expressions of gluten sensitivity are determined by genetic factors, and hence how feasible they are for genetic mapping; therefore, we studied all six monozygous twin pairs found among 1292 prospectively collected patients of dermatitis herpetiformis in Finland. Three of the six twin pairs were concordant for dermatitis herpetiformis and for simultaneous enteropathy, celiac disease. Two other twin pairs were partially discordant, one of each pair had dermatitis herpetiformis and celiac disease, whereas the other had solely the gut manifestation of gluten sensitivity, i.e., celiac disease. Only one pair was found to be discordant for gluten sensitivity. All the pairs had typical risk alleles for gluten sensitivity, i.e., either HLA DQ2 or DQ8. These results demonstrate that the genetic component in gluten sensitivity as broadly defined is very strong (5/6 concordant). Genetically identical individuals can have clearly distinguished phenotypes, either dermatitis herpetiformis or celiac disease, suggesting that environmental factors determine the exact phenotype of this multifactorial disease. These findings are of importance in genetic linkage analyses, which focus to only certain phenotypic properties of a complex trait.

Decreased numbers of circulating plasmablasts and differences in IgA1-plasmablast homing to skin in coeliac disease and dermatitis herpetiformis

“…DH, whereas others with the same genetic background develop only gluten enteropathy without the rash and immunoglobulin (Ig)A1 deposits, i.e. CD [7].…”

Genome-wide linkage analysis of Scandinavian affected sib-pairs supports presence of susceptibility loci for celiac disease on chromosomes 5 and 11

“…Furthermore, the concordance rate of monozygotic twins is significantly higher than that of HLA-identical dizygotic twins (30%), (Romino et al, personal communication). 5,6 Assuming a multiplicative model of disease predisposing genes, the overall importance of non-HLA genes has been calculated to be greater than that of the HLA genes. 3,7 Despite this, knowledge about non-HLA genes that predispose to CD is scarce.…”

Genetic dissection between coeliac disease and dermatitis herpetiformis in sib pairs

“…E-mail : jukka.partanen!bts.redcross.fi genetic component is important too, as approximately 10-19 % of first-degree relatives are affected (Mearin et al 1983 ;Auricchio et al 1988 ;Hervonen et al 2002). Twin studies (Polanco et al 1981 ;Bardella et al 2000 ;Hervonen et al 2000) and studies of HLA identical sibs (Petronzelli et al 1997) have also indicated the importance of genetic factors. The only genetic locus indisputably associated with cCD and DH is the HLA DQ on chromosome 6.…”

“…As genetically identical twins can differ in outcome between cCD and DH (Walker-Smith, 1973 ;Jepsen & Ullman, 1980 ;Kosnai et al 1985 ;Hervonen et al 2000) this may be determined, at least in some cases, solely by environmental factors. …”