Inheritance of low serum immunoglobulin D

Area of Science:

• Immunogenetics
• Human Genetics
• Immunology

Background:

• Serum Immunoglobulin D (IgD) levels in normal individuals exhibit non-unimodal distributions.
• Previous research indicates potential non-genetic factors influencing IgD levels, necessitating further investigation into hereditary components.

Purpose of the Study:

• To determine if inheritance plays a role in the determination of serum IgD levels.
• To investigate the genetic basis of low Immunoglobulin D (IgD) levels in the human population.

Main Methods:

• Measured IgD levels in serum/plasma from 301 children, 245 adult blood donors, and 134 first-degree relatives of individuals with low IgD.
• Analyzed distributions of log IgD levels and performed sibling-sibling correlation analysis.
• Conducted segregation and pedigree analyses on data from first-degree relatives.

Main Results:

• Log IgD levels in randomly selected children and adults showed non-unimodal distributions with nadirs at 2.15 IU/ml.
• Approximately 13-14% of the general population exhibited low IgD values (<2.15 IU/ml).
• A significant sibling-sibling correlation (r=0.56) for log IgD levels was observed, and segregation analyses supported autosomal recessive inheritance for low IgD.

Conclusions:

• The non-unimodal distribution and familial aggregation of IgD levels suggest a genetic influence.
• Results are compatible with autosomal recessive inheritance of an allele associated with low plasma IgD levels.
• This study provides evidence for a specific genetic mechanism underlying low IgD concentrations in humans.