HLA and disease 1982--a survey.

Area of Science:

• Immunogenetics
• Human Genetics
• Disease Association Studies

Background:

• Recent HLA (Human Leukocyte Antigen) research indicates a shift in disease associations from HLA-A/B to HLA-D/DR antigens.
• This shift supports the role of immune response (Ir) and immune suppression (Is) genes in autoimmune diseases.
• Ankylosing spondylitis is an exception, maintaining a stronger association with HLA-ABC antigens.

Purpose of the Study:

• To review recent advancements in HLA and disease association studies.
• To highlight newly identified HLA associations with specific conditions.
• To discuss the genetic basis of disease susceptibility, particularly in relation to HLA.

Main Methods:

• Review of recent HLA and disease association studies.
• Analysis of genetic associations with specific diseases including ankylosing spondylitis, Zwa antigen immunization, IgA deficiency, idiopathic hemochromatosis, and congenital adrenal hyperplasia.
• Evaluation of genetic models for disease inheritance.

Main Results:

• Most diseases previously linked to HLA-A/B are now more strongly associated with HLA-D/DR antigens.
• New associations include maternal immunization against Zwa antigen, IgA deficiency, idiopathic hemochromatosis, and congenital adrenal hyperplasia.
• HLA-B27 confers dominant susceptibility to ankylosing spondylitis.
• HLA's role in Insulin-Dependent Diabetes Mellitus (IDDM) susceptibility is strong, but simple genetic models are unlikely; two susceptibility genes within HLA remain a possibility.

Conclusions:

• HLA-D/DR antigens are increasingly implicated in disease associations, particularly autoimmune conditions.
• Specific HLA factors like HLA-B27 are critical for certain disease susceptibilities.
• Further research is needed to clarify the complex genetic mechanisms underlying HLA-associated diseases like IDDM.