Clinical immunohematology: Anti-Rh (anti-D) antibodies produced after exposure to Rh-positive red blood cells primarily belong to which immunoglobulin class?

Introduction / Context:
In transfusion medicine and maternal–fetal medicine, the class of antibodies directed against Rh (D) antigen determines their ability to cross the placenta and cause hemolytic disease of the fetus and newborn. Correctly identifying anti-Rh as predominantly IgG has major clinical implications.

Given Data / Assumptions:

• Anti-Rh (anti-D) antibodies arise after sensitization to Rh-positive erythrocytes.
• Placental transfer occurs via Fc receptors specific for IgG.
• We are focusing on the clinically significant, high-affinity response.

Concept / Approach:
Anti-Rh antibodies are class-switched, affinity-matured IgG, typically IgG1 and IgG3 subclasses. These efficiently cross the placenta, opsonize fetal red cells, and can activate complement or mediate Fc receptor–dependent destruction. While early responses to many antigens may include IgM, the clinically important anti-D antibodies that cause hemolysis are IgG.

Step-by-Step Solution:
Recognize that Rh antigens are proteinaceous and provoke T cell–dependent responses. Recall class switching to IgG in secondary responses with memory B cells. Note placental transfer of IgG explains fetal risk. Select IgG as the predominant class.

Verification / Alternative check:
Antiglobulin (Coombs) testing detects bound IgG on fetal or maternal red cells. Rho(D) immune globulin prophylaxis uses IgG anti-D to prevent maternal sensitization.

Why Other Options Are Wrong:

• IgM: Does not cross placenta; initial low-affinity responses are less clinically significant here.
• IgA: Mucosal; not a driver of hemolysis in Rh disease.
• IgE / IgD: Involved in allergy or B-cell receptor, not hemolytic disease.

Common Pitfalls:
Assuming all first antibodies are IgM; anti-D of clinical concern is IgG after class switching. Also, conflating ABO hemolysis (often IgM) with Rh disease (IgG).

Final Answer:
IgG type.