Antibodies in Blood Banking

Overview

Understanding a few concepts of IgG and IgM are essential to appreciate the concepts of clinical significance and routine blood bank testing methodologies.

Section Goals

  • Differentiate characteristics of IgG and IgM antibodies.

Antibodies: IgM, IgG, and IgA

Some IgM antibodies, like those in the ABO blood group system, occur naturally. These ABO antibodies arise from exposure to environmental factors containing A and B-like substances, such as pollen and intestinal flora. They react with red blood cell antigens despite not being directly stimulated by them. Additionally, immune-related IgM antibodies develop after exposure to red cell antigens through transfusion or pregnancy.

Simplified structural differences of IgM vs IgG

IgM antibodies tend to demonstrate optimal reactivity at room temperature and colder temperatures. Therefore, they typically do not induce hemolytic transfusion reactions, which occur at body temperatures of 37°C. In addition, IgM is a large pentamer molecule, and therefore, does not cross the placenta and is not associated with Hemolytic Disease of the Fetus and Newborn (HDFN). For these reasons, IgM is generally considered to be not clinically significant. However, some IgM antibodies, notably naturally occurring ABO antibodies, are clinically significant as they bind complement and lead to intravascular hemolysis.

IgG antibodies, although smaller in size, are often clinically significant as they react at body temperature (37°C). Many IgG antibodies can cross the placenta and induce shortened red cell survival through intravascular or extravascular hemolysis. Therefore, they are capable of causing HDFN.

There are four subclasses of IgG (IgG1, IgG2, IgG3, and IgG4). IgG1 and IgG3 have the potential to fix complement and cause intravascular hemolysis, while IgG2 and IgG4, although unable to fix complement, can still shorten red blood cell survival through extravascular means, where the IgG antibodies opsonize target cells and extravascular macrophages (e.g., hepatic or splenic macrophages) cull the cell from circulation.

IgA antibodies are typically insignificant in Transfusion Medicine, but antibodies to IgA (i.e., anti-IgA) can provoke severe allergic transfusion reactions and anaphylaxis.

Primary and Secondary (Anamnestic) Response

When encountering a foreign red cell antigen, the immune system may produce antibodies in response, influenced by the antigen’s immunogenicity. The primary response typically takes 21-30 days, with the initial antibody produced being IgM. Over time, the response transitions to generating IgG antibodies. Subsequently, long-lived memory B cells are formed. Upon re-exposure to the same antigen, the body mounts a faster response (1 to 2 days), known as a secondary or anamnestic response, characterized by a rapid increase in predominantly IgG antibody production.

Primary Response occurs upon first exposure to a foreign antigen and takes 21-30 days to develop. Initial antibody produced is IgM, but in time production switches to IgG and memory B-cells are formed. Secondary Response is triggered by re-exposure to the same antigen with a faster response occurring within 1-2 days and is characterized by a rapid increase in IgG antibody production.

Complement

In the context of blood banking, complement refers to a group of proteins that are part of the body’s immune system. Complement proteins play a crucial role in the immune response by enhancing the ability of antibodies to eliminate pathogens and foreign substances, including incompatible blood cells.

When antibodies bind to their target antigens on foreign red blood cells, they can activate the complement system. This activation triggers a cascade of biochemical reactions that result in several outcomes:

  1. Opsonization: Complement proteins coat the surface of the target cells, marking them for destruction by immune cells such as macrophages.
  2. Cell Lysis: The complement cascade can form a membrane attack complex (MAC), which creates pores in the membranes of target cells, leading to their destruction through osmotic lysis.
  3. Inflammation: Complement activation can lead to the release of inflammatory mediators, recruiting immune cells to the site of antigen-antibody interaction.

In the context of blood transfusions, complement activation can be both beneficial and harmful. Beneficially, complement activation aids in the clearance of incompatible red blood cells, reducing the risk of transfusion reactions. However, excessive complement activation can lead to adverse reactions, such as acute hemolysis of transfused red blood cells, which can result in severe complications for the recipient.

Therefore, understanding complement activation is essential in blood banking to ensure safe and compatible transfusions. Techniques such as blood typing and crossmatching are used to identify compatible donor blood and minimize the risk of complement-mediated transfusion reactions.

As mentioned above, and you’ll want to remember this: IgM is capable of fixing complement and may be associated with clinically significant intravascular hemolysis, whereas only a few subclasses of IgG (IgG1 and IgG3) have the potential to fix complement and cause intravascular hemolysis.

Key takeaways:

  • IgM is a big pentamer, and therefore, cannot cross the placenta and is not associated with HDFN.
  • IgG is a smaller molecule that can cross the placenta, and therefore, may be associated with HDFN.
  • IgM is capable of fixing complement and may be associated with clinically significant intravascular hemolysis.
  • Only a few subclasses of IgG (IgG1 and IgG3) have the potential to fix complement and cause intravascular hemolysis.
  • The first exposure to a foreign antigen that results in antibody production is called the “Primary Response” and typically takes 21-30 days, with the initial antibody produced being IgM. Over time, the response transitions to generating IgG antibodies. Subsequently, long-lived memory B cells are formed.
  • If exposed to the same foreign antigen again at some point in the future, the body mounts a faster response in as little as 1 to 2 days. This is known as a “Secondary Response” or “Anamnestic Response” and is characterized by a rapid increase in predominantly IgG antibody production.