HLA and Disease Association

An interesting application of HLA in medicine was the description of the increased incidence of some HLA class-I and class-II alleles in patients with a particular disease (Tiwari and Terasaki, HLA and disease associations. Springer Verlag, New York, 1985). Amiel reported for the first time that “the HLA antigens B5 + B35 + B18 are found more frequently in patients with Hodgkin’s disease (51%) compared to healthy individuals (27%)”. This report was presented at the Turin HLA workshop ((Amiel, Histocompatibility Testing 1967. Munksgaard, Copenhagen)). It was the beginning of a “long journey” of analysing the HLA allele frequency in a variety of diseases. Many of these diseases are associated with autoimmune responses ((Bell et al., Adv Hum Genet 18:1–4, 1989); (Thorsby and Lie, Transpl. Immunol. 14:175–182, 2005)). Several decades have passed since this report, and yet molecular mechanisms that are responsible for these associations are still not clearly identified, with one exception “the celiac disease”. I will further discuss in detail five diseases that are associated with HLA to demonstrate their complexity and our ignorance about their aetiopathogenesis. These diseases are (a) ankylosing spondylitis, (b) celiac disease, (c) insulin-dependent diabetes, (d) narcolepsy and (e) rheumatoid arthritis.