How to conduct research of rare autoimmune diseases

Rare autoimmune diseases are difficult to conduct researches in spite of present era with advanced scientific progress. Research using genetic approach is a promising way since genetic findings implicate causality of diseases. Still, there are multiple obstacles preventing genetic studies of rare diseases. Here, we list up the problems and propose solutions for them with detailed examples. The biggest problem is that it is difficult to collect a substantial number of DNA samples from patients with rare diseases. We propose to collaborate not only with academic institutions and hospitals but with patients’ groups. Detailed examples include studies about Takayasu arteritis (TAK), relapsing polychondritis, and systemic sclerosis. In TAK, we identified IL12B, a key gene which seems to play a central role in the disease. After getting evidence of IL12p40 encoded by IL12B as a possible therapeutic target by showing similarities of the genetic background between TAK and ulcerative colitis, we performed a pilot clinical study of ustekinumab, a monoclonal antibody against IL12p40 for patients with refractory TAK and obtained good response. This is a good example of how genetic findings in a rare disease lead to development of new therapeutic option.