Comparing CHC and healthy donors, Spaan M et al. found no difference in the frequency of circulating CD4+CXCR5+ CXCR5+, CXCR5+PD-1+, CXCR5+ICOS+, and CXCR5+PD-1+ICOS+ subsets of CD4+ T cells between the groups [58]. This evidence concerns the gene ICOS and cryohydrocytosis.