Detailed analyses within the chromosomal region showed that linkage disequilibrium (LD) exists between CD28, CTLA-4, and ICOS, and a common haplotype is found very frequently among patients with autoimmune diseases and celiac disease.[44–46] As the existence of LD between CTLA-4 and these two closely linked genes may mask the true causative risk allele for autoimmune disease, we cannot exclude that a single true disease-causing allele in CTLA-4 or another neighboring gene might be found in this chromosome region. Here, ICOS is linked to autoimmune disease.