IMMUNOGLOBULIN D: STRUCTURE, FUNCTION AND NORMAL VALUES - BIOLOGY - 2024

The immunoglobulin D (IgD), discovered in 1965, is a surface immunoglobulin which is (along with IgM) on the membrane of B cells (migd) before activation.

It has its function as the initial receptor for antigens. IgD is also free in plasma thanks to its secretion (sIgD). It has a molecular weight of 185,000 Daltons and represents about 1% of the immunoglobulins in an organism.

Figure 1. Three-dimensional structure of an immunoglobulin or antibody. Source: By UnknownUnknown author, via Wikimedia Commons

What are immunoglobulins?

Immunoglobulins or antibodies are highly specific complex globular glycoproteins synthesized by B lymphocytes, cells responsible for the immune response in the body of animals.

Immunoglobulins interact with molecules that the body identifies as non-self or antigens. Any substance capable of activating the immune response in the body is called an antigen.

The family of Ig antibody molecules includes those circulating in blood plasma and those on the surface of B lymphocytes prior to their activation.

There are five types of immunoglobulins: IgG, IgD, IgE, IgA and IgM (identified in humans, mice, dogs, reptiles, fish, among others), which differ structurally by their constant regions in the heavy chain. These differences give them particular functional properties.

Antibodies act as specific sensors for antigens. With these they form complexes that initiate a cascade of reactions typical of the immune system. The general stages in this process are: recognition, differentiation of the specific lymphocytes and finally the effector stage.

Structure

Since IgD has been evolutionarily preserved from cartilaginous fish (which populated the planet about 500 million years ago) to humans, it is believed to serve vital immune functions.

Despite this, it has been the least studied of the immunoglobulins, which is why the specific functions of sIgD in serum are not yet known exactly, while several functions have been proposed for mIgD.

sIgD

One of the causes of the recent interest in the study of sIgD has been the finding of high levels of this Ig in some children with periodic fever. In turn, another factor of interest is its usefulness in monitoring myelomas.

SIgD is believed to play a role in blood, mucosal secretions, and on the surface of innate immune effector cells, such as basophils.

They are highly reactive against pathogens of the respiratory system and their excretion products. IgD has been reported to increase mucosal immunity, thanks to its effect on bacteria and viruses present.

mIgD

Regarding mIgD, it is considered a membrane antigen receptor for B lymphocytes, which would favor cell maturation. In turn, it is believed to be a ligand for IgD receptors in the immunoregulation of T helper cells.

B lymphocytes

IgD-producing B lymphocytes are believed to represent a particular cell lineage called B-1 lymphocytes. These are self-reactive lymphocytes that have escaped the clonal deletion.

The autoantibodies generated by these lymphocytes react with deoxyribonucleic acid or DNA (single and double-stranded), with cell receptors, the cell membranes of red blood cells and epithelial tissue.

This is how they generate autoimmune diseases, such as systemic lupus erythematosus, myasthenia gravis, autoimmune hemolytic anemia and idiopathic thrombocytopenia purpura.

Immune-inflammatory system

IgD is also known to be involved in the orchestration of a system that interferes between the immune and inflammatory systems: high concentrations of IgD are related to autoinflammatory disorders (hyperimmunoglobulemia syndrome D, HIDS or hyper-IgD).

For example, in patients with autoimmune conditions, such as rheumatoid arthritis, elevated values ​​of both sIgD and mIgD are found. It is therefore believed that this condition contributes to the pathogenesis of the disease.

The possible functions of this antibody in peripheral blood mononuclear cells (PBMC) from these patients are currently being studied. All this has led to consider that IgD could be a potential immunotherapeutic target in the treatment of rheumatoid arthritis.

Normal values

The sIgD in normal individuals varies widely, which has made it difficult to establish an accurate reference interval for their normal concentrations. Some studies have shown that this variation is particularly influenced by:

1. The sensitivity of the applied detection technique -both by radioimmunoassays (RIA), enzyme immunoassays (EIA) and the one most commonly used in clinical laboratories which is radioimmunodiffusion (RID) -.
2. The absence of a single stipulated universal method for the detection of IgD.
3. Hereditary factors, race, age, sex, pregnancy status, smoking status, among others

Some specialists even consider that the routine analysis of IgD is not justified, because its specific role is far from being elucidated and the costs of its analysis in the clinical laboratory are high. It would only be justified in cases of patients with serum monoclonal IgD or suspected of having HIDS.

Serum concentration

On the other hand, it is known that sIgD generally has a serum concentration lower than that of IgG, IgA and IgM, but higher than the concentration of IgE.

Furthermore, because it has a half-life of 2 to 3 days, the plasma concentration is less than 1% of the total immunoglobulin in serum. Some research indicates that it represents 0.25% of total serum immunoglobulins.

Blood values

Among the reported values ​​of sIgD in blood, in newborns it has been 0.08 mg / L (determined by RIA), in infants and adults it varies from undetectable values ​​to 400 mg / L (depending on age and individuals of each individual).

In normal adults they have been reported as normal averages 25; 35; 40 and 50 mg / L. In general terms, the mean serum concentration for healthy adults has been reported as 30 mg / L (determined by RID).

However, as discussed in this article, there are many factors that prevent a standard normal range from being established.

References

1. Chen, K. and Cerutti, A. (2011). The function and regulation of immunoglobulin D. Current opinion in immunology, 23 (3), 345-52.
2. Harfi, AH and Godwin, JT (1985). Normal serum levels of IgG, IgA, IgM, IgD, and IgE in Saudi Arabia. Annals of Saudi Medicine, Vol 5, No. 2.99-104. doi: 10.5144 / 0256-4947.1985.99
3. Josephs, SH and Buckley, RH (1980). Serum IgD concentrations in normal infants, children, and adults and in patients with elevated IgE. The Journal of Pediatrics, Vol. 96, No. 3, pp 417-420.
4. Vladutiu, AO (2000). Immunoglobulin D: properties, measurement, and clinical relevance. Clinical and diagnostic laboratory immunology, 7 (2), 131-40.
5. Voet, JG and Voet, WPD (2005). Fundamentals of Biochemestry: Lyfe at the Molecular Level. Wiley. pp 1361.
6. Wu, Y., Chen, W., Chen, H., Zhang, L., Chang, Y., Yan, S., Dai, X., Ma, Y., Huang, Q. and Wei, W. (2016). The elevated secreted immunoglobulin D enhanced the activation of peripheral blood mononuclear cells in rheumatoid Arthritis. PloS one, 11 (1). doi: 10.1371 / journal.pone.0147788