A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen

Autoantigen discovery is a critical challenge for the understanding and diagnosis of autoimmune diseases. While autoantibody markers in current clinical use have been identified through studies focused on individual disorders, we postulated that a reverse approach starting with a putative autoantigen to explore multiple disorders might hold promise. We here targeted the epidermal protein transglutaminase 1 (TGM1) as a member of a protein family prone to autoimmune attack. By screening sera from patients with various acquired skin disorders, we identified seropositive subjects with the blistering mucocutaneous disease paraneoplastic pemphigus. Validation in further subjects confirmed TGM1 autoantibodies as a 55% sensitive and 100% specific marker for paraneoplastic pemphigus. This gene-centric approach leverages the wealth of data available for human genes and may prove generally applicable for biomarker discovery in autoimmune diseases.

A Sinister Disease Hides Behind Recalcitrant Mucocutaneous Disorder

Paraneoplastic pemphigus (PNP) is a rare autoimmune disorder associated with underlying benign or malignant neoplasia. Its signs and symptoms may be the first presentation of a concealed malignancy. Due to late diagnosis, prognosis of PNP is not good, so early diagnosis and treatment is of paramount importance. We present a case of 22 years old female who presented to our out patient department (OPD) with history of recurrent, severe, recalcitrant, painful oral ulcers; lichenoid lesions over the hands and feet and widespread blistering and erosions involving the soles. Histopathological examination was consistent with paraneoplastic pemphigus and showed features of lichenoid dermatitis. CT scan revealed retroperitoneal mass suggestive of Castleman disease. The patient was referred to surgical team for further management.

The pemphigus group – diseases and their treatment possibilities

The diseases of the pemphigus group are chronic conditions belonging to the autoimmune blistering disorders. They appear with characteristic skin and mucous membrane symptoms. Their major forms are pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. The aim of this review is to present the diseases of the pemphigus group and to summarize the latest therapeutic options with the exception of paraneoplastic and IgA pemphigus that are discussed separately