New insights into disease that causes skin blistering

The latest research concerning pemphigus, a life-threatening blistering disorder of the skin and mucous membranes, may help lead to a better understanding of the immunopathogenesis of disease and to more specifically targeted therapeutic approaches, according to Aimee Payne, M.D., Ph.D., of the department of dermatology, University of Pennsylvania, Philadelphia.

Background

Pemphigus is an autoimmune blistering disorder of the skin and/or mucous membranes caused by antibodies against cell surface desmosomal adhesion molecules known as desmogleins (Dsgs).

Little is known about the individual autoantibodies in patients with active disease. Therefore many questions remain, such as: Are there multiple B-cell clones producing many different pathogenic and non-pathogenic antibodies, or are there a limited number of these pathogenic clones?

"Ultimately, a better understanding of pemphigus pathophysiology and more specific treatments will require a detailed genetic investigation of how pathogenic autoantibodies develop within patients," she says.

The study

A recent study by Dr. Payne and her co-workers from the University of Pennsylvania departments of dermatology and pathology (J Clin Invest. 2005;115:888-899) describes the use of phage display technology to clone and genetically characterize anti-desmoglein antibodies from a patient with active mucocutaneous pemphigus vulgaris (PV).

RNA from the peripheral blood lymphocytes of a PV patient was used to amplify cDNA encoding all the expressed antibody variable regions, which are the portions of the antibody that specifically bind antigen. The DNA was then introduced into phage, which are viruses that infect bacteria.

For the study, the Dsg-specific antibodies were selected out of the library by binding to plates containing Dsg3 or Dsg1. The non-specific antibodies were washed away, and then individual anti-Dsg phage clones, each representing a single monoclonal antibody, were purified for sequencing and biochemical characterization.

Results

"Although these antibodies were isolated from only a single patient, they were inhibited from binding to Dsg3 and/or Dsg1 by multiple other pemphigus patients' sera, including patients with pemphigus foliaceus (PF), suggesting that antibody binding motifs, or 'idiotypes,' are shared among pemphigus patients," Dr. Payne explains.