Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (992 page)

   How do HLA antigens confer disease susceptibility? Data regarding the relationship of HLA antigens to disease susceptibility remain at the level of associations, not disease mechanisms. Nevertheless, HLA associations that are reproducible and robust provide important clues about the development of certain rheumatic diseases. A variety of models have been postulated to explain these associations functionally. These include the importance of HLA polymorphisms in:

   Shaping the T-cell repertoire during development

   Shaping the peripheral T-cell repertoire

   Determining which antigenic peptides are bound and, therefore, presented to the immune system for recognition

   Generating molecular mimicry between self antigens and either the HLA molecule itself or peptides that it recognizes

   Affecting HLA protein presentation of either foreign or self-antigenic peptides to autoreactive T cells

   Influencing how infection, exogenous agents, or “molecular mimicry” may reactivate silenced T cells in autoimmune diseases

   Affecting immune suppression and cancer development in important ways through the loss of HLA gene expression because of viral infection, somatic mutations, or other causes

   Influencing antigen processing and presentation

   Identification of the mechanistic basis of these disease associations may lead to novel and specific treatments, as well as preventive strategies.

   
Listed
below
are some of the current known disease associations based on various publications
:

   
Ankylosing spondylitis
:
HLA-B*27
(especially
HLA-B*27:05
)

   
Celiac disease
:
HLA
-
DQA1*05-DQB1*02:01, DQA1*03-DQB1*03:02