Diagnosis:
Immunogenetics: HLA Association With Disease
• Multiple human diseases are associated with human leukocyte antigen (HLA) alleles.
• It is important to understand the difference between association and causation; HLA alleles associated with diseases may not always be pathogenic themselves. The culprit may be other (non-HLA) alleles specific to a human population, which also happens to be characterized by a high frequency of certain HLA alleles.
• In the case of DQB1*06:02, it is one of the strongest disease associations of an HLA allele described. Some 90% to 100% of patients with definite cataplexy carry this allele.
• The pathogenic role of HLA-DQB1*06:02 has not been fully elucidated, but as in all HLA-disease associations, an autoimmune mechanism is strongly suspected.
• Recent studies describe a deficiency in hypocretin-secreting neurons in the hypothalamus of narcoleptic patients. HLA-DQB1*06:02 was shown to bind hypocretin with high affinity, and presumably present it to T cells, triggering an autoimmune response.
