HLA and autoimmunity

No other locus carries as many and as strong genetic risks for autoimmune disease as the HLA region. Individual HLA alleles tip the risk for very specific diseases. Because Genome types the HLA loci, these associations can be placed directly.

HLA TYPE ASSOCIATED DISEASE HLA-DQ2 / DQ8 Celiac disease HLA-DR3-DQ2 / DR4-DQ8 Type 1 diabetes HLA-DRB1*15:01 Multiple sclerosis HLA-DRB1 Shared Epitope Rheumatoid arthritis HLA-B27 Ankylosing spondylitis HLA-DQB1*06:02 Narcolepsy HLA-C*06:02 Psoriasis Association means elevated risk, not diagnosis; most carriers never fall ill.

Why HLA in particular

HLA molecules decide which fragments of proteins are shown to T cells. Which alleles a person carries therefore sets which self and foreign peptides are visible at all. Even small differences in the binding groove shift whether the immune system tolerates or attacks a structure.

How the risk arises

Several mechanisms interlock: certain alleles present autoreactive peptides particularly well, they influence the selection of T cells in the thymus, and through molecular mimicry pathogen peptides can resemble self. In the example of EBV and multiple sclerosis, viral triggers and HLA predisposition come together.

Read with caution

A risk allele is neither necessary nor sufficient for disease. Some associations are strong (HLA-B27, HLA-DQ2), many weak and population-dependent. Genome shows the HLA types and the documented associations as technical evidence, not as a diagnosis.

What Genome measures. Which risk-raising or protective HLA alleles are present in the typing, set against documented disease associations. A context layer on top of HLA typing, not a separate measurement.

Related topics

HLA typingCeliac diseaseMultiple sclerosisDisease associations

Sources

  1. 1Matzaraki et al., 2017 The MHC locus and genetic susceptibility to autoimmune and infectious diseases. Genome Biology 18:76. doi.org/10.1186/s13059-017-1207-1
  2. 2Dendrou et al., 2018 HLA variation and disease. Nature Reviews Immunology 18:325–339. doi.org/10.1038/nri.2017.143
  3. 3Trowsdale & Knight, 2013 Major histocompatibility complex genomics and human disease. Annual Review of Genomics and Human Genetics 14:301–323. doi.org/10.1146/annurev-genom-091212-153455