Autoantibodies Against the Immunodominant Bullous Pemphigoid Epitopes Are Rare in Patients With Dermatitis Herpetiformis and Coeliac Disease

Abstract

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of coeliac disease (CD). Patients with DH have an elevated risk of development of another autoimmune blistering skin disease, bullous pemphigoid (BP). In this study we investigated whether patients with DH and CD (mean age for both 49 years) have circulating autoantibodies against BP180, the major BP autoantigen. ELISA tests showed that only a few DH (3/46) and CD (2/43) patients had BP180-NC16A IgG autoantibodies. Immunoblotting found that more than half of the DH samples contained IgG autoantibodies against full-length BP180. Epitope mapping with 13 fusion proteins covering the BP180 polypeptide revealed that in DH and CD patients, IgG autoantibodies did not target the NC16A or other epitopes typical of BP but recognized other intracellular and mid-extracellular regions of BP180. None of the analyzed DH and CD patients with either ELISA or immunoblotting positivity had IgG or IgA reactivity against the cutaneous basement membrane in indirect immunofluorescence analysis or skin symptoms characteristic of BP. Although only a minority of middle-aged DH patients had IgG autoantibodies against the immunodominant epitopes of BP180, our results do not exclude the possibility that intermolecular epitope spreading could explain the switch from DH to BP in elderly patients.

Use of gliptins reduces levels of SDF-1/CXCL12 in bullous pemphigoid and type 2 diabetes, but does not increase autoantibodies against BP180 in diabetic patients

“…Almost equal shares of BP180-NC16A ELISA positive and negative T2D+g and T2D samples recognized FL-BP180 in immunoblotting. Also 46% of the healthy control sera detected FL-BP180, which is in accordance with previous findings of our group and others ( 36 , 40 ). Our previous immunoblotting works have shown that FL-BP180 is frequently recognized by serum samples from patients with Alzheimer’s disease, multiple sclerosis, dermatitis herpetiformis and coeliac disease.…”

“…Our previous immunoblotting works have shown that FL-BP180 is frequently recognized by serum samples from patients with Alzheimer’s disease, multiple sclerosis, dermatitis herpetiformis and coeliac disease. Of note is that those samples displayed various proportions of BP180-NC16A ELISA positive and negative sera ( 28 , 30 , 36 ). The high proportion of FL‐BP180 recognition in immunoblotting could be explained by the fact that the Alzheimer’s disease and T2D populations tend to be older than those with the other conditions.…”

“…FL-BP180 was expressed in COS7 cells transfected with human BP180 cDNA ( 35 ) and prepared as described previously ( 36 ). Fifty ng of each recombinant human glutathione-S-transferase (GST)-BP180-fusion protein expressed in E. coli spanning most of the BP180 polypeptide were used as an antigen.…”

“…The numbers of immunohistochemically stained SDF-1 positive cells in the skin samples were compared using the Kruskal-Wallis test with Dunn’s corrected P values for multiple comparisons. In epitope mapping, antibody-detected bands were densitometrically analyzed using the ImageJ software package (NIH, Bethesda, MD, USA) and classified in an ordinal scale: “0” = no band, “1” = weak, “2” = strong, “3” = very strong, as described previously ( 36 ). Differences between groups in epitope mapping were compared pairwise using the Fisher-Freeman-Halton exact test.…”