We have investigated DNA polymorphism of the class II alpha chain genes in HLA typed patients with insulin dependent diabetes mellitus (IDDM; n = 79), celiac disease (CD; n = 46), dermatitis herpetiformis (DH; n = 53), and controls (n = 86).
We investigated polymorphism of HLA-DP genes in three DR3 related diseases, confirming an association of coeliac disease with a Bgl II DP alpha polymorphism (a restriction fragment sized 3.5 kb present in 75% of patients compared to 34% of control subjects, p less than 0.001), and finding a weaker association with dermatitis herpetiformis (57% v 34%, p = 0.01) and no association with insulin dependent diabetes mellitus.
Further, they indicate that a specific DQ molecule, when present in combination with the product of one of several different DPB1 alleles, may contribute to susceptibility to the intestinal lesion, which is common to dermatitis herpetiformis and celiac disease.
To test this hypothesis, we performed DNA sequence analysis on the highly polymorphic HLA-DQB1 and HLA-DQA1 loci of eight patients with dermatitis herpetiformis.
HLA-DQ allelic typing by restriction fragment length polymorphism analysis of PCR-amplified HLA-DQA1 and HLA-DQB1 fragments was also performed in ten patients with DH to determine the allelic distribution among both HLA-DR3 (eight patients) and non-DR3 (two patients) DH patients.
To evaluate the role of other genes, 36 Northern Italian children with DH were analysed for DNA polymorphisms at HLA-DP and immunoglobulin (Ig) heavy chain loci.
Polymorphisms of the HLA-DP region loci have been shown to associate with autoimmune diseases which share immunological features with IgAN; coeliac disease (CD) and dermatitis herpetiformis (DH).
Since functional studies have associated the rare TNFB*1 and TNF2 alleles with a higher secretion of TNF upon activation in vitro, the predominance of these two 'high-response' TNF alleles in DH patients may represent a genetic basis for the chronic inflammatory response in the skin and mucosal tissues of patients with DH.
Since functional studies have associated the rare TNFB*1 and TNF2 alleles with a higher secretion of TNF upon activation in vitro, the predominance of these two 'high-response' TNF alleles in DH patients may represent a genetic basis for the chronic inflammatory response in the skin and mucosal tissues of patients with DH.
Although TNF2 is strongly associated with dermatitis herpetiformis, this was weaker than the association with the class II loci, with DQw2 (DQB1*0201/DQA1*0501) showing the strongest disease association.
We therefore examined TNF-alpha genotypes in patients with dermatitis herpetiformis and controls and compared the association with that of the class II alleles.
Because dermatitis herpetiformis is characterized by neutrophilic inflammation and destructive changes in the basement membrane zone, we studied the in situ expression of interstitial collagenase and stromelysin-1 in 11 lesions.
Collagenase, stromelysin-1, and urokinase-type plasminogen activator were not expressed in normal-appearing skin of patients with dermatitis herpetiformis.
The expression of VPF/VEGF mRNA was strongly up-regulated in the lesional epidermis of bullous pemphigoid (n = 3), erythema multiforme (n = 3), and dermatitis herpetiformis (n = 4) as detected by in situ hybridization.
Dermatitis herpetiformis (DH) and coeliac disease (CD) are gluten-sensitive diseases which have a common immunogenetic background, with the histocompatibility locus antigen (HLA) alleles DQ A1*0501 and B1*0201 in the short arm of chromosome 6.
Expression of interleukin-4 and interferon-gamma in the small bowel of patients with dermatitis herpetiformis and isolated gluten-sensitive enteropathy.
Furthermore, human macrophage metalloelastase was expressed by macrophages in areas with disrupted basement membrane, as assessed by type IV collagen staining, in pityriasis lichenoides and dermatitis herpetiformis.
Expression of interleukin-4 and interferon-gamma in the small bowel of patients with dermatitis herpetiformis and isolated gluten-sensitive enteropathy.