HLA & immunogenetics

HLA and autoimmunity

The HLA region contains many variants associated with autoimmune diseases in research. HLA alleles can influence relative risk, but the strength and relevance vary by disease and population. Genome presents typed HLA alleles alongside documented associations, not as a diagnosis.

Key points

  • HLA variants are involved in many autoimmune diseases, with effects that differ by condition.
  • HLA molecules influence which peptides immune cells can recognize.
  • An association is not a diagnosis; many carriers of a risk allele do not develop the disease.
HLA TYPEASSOCIATED DISEASEHLA-DQ2 / DQ8Celiac diseaseHLA-DR3-DQ2 / DR4-DQ8Type 1 diabetesHLA-DRB1*15:01Multiple sclerosisHLA-DRB1 Shared EpitopeRheumatoid arthritisHLA-B27Ankylosing spondylitisHLA-DQB1*06:02NarcolepsyHLA-C*06:02PsoriasisAssociation means elevated risk, not diagnosis; most carriers never fall ill.

Why HLA in particular

HLA molecules present selected peptides to T cells. Differences between alleles can change which peptides bind and are presented, and may influence immune responses. This alone does not show whether the immune system will attack a person's own tissue.

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