IMMUNOGLOBULINS

• Immunoglobulins (Igs) are γ-globulins, the most common types of globulins in the blood; therefore an elevation in Igs (hypergammaglobulinemia) often raises the total protein level and might cause significant clinical symptoms.
• Igs are antibodies which play important roles in humoral immune response.
• A normal Ig is composed of 2 heavy chains (HCs) and 2 light chains (LCs).
• There are 5 major types of HCs (γ, ε, δ, α, and μ) and 2 types of LCs (κ and λ).
• There are 5 major Ig isotypes, classified based on 5 major types of HCs:
   IgG = 2 γ HCs + 2 LCs (either κ or λ)
   IgE = 2 ε HCs + 2 LCs (either κ or λ)
   IgD = 2 δ HCs + 2 LCs (either κ or λ)
   IgA = 2 α HCs + 2 LCs (either κ or λ)
   IgM = 2 μ HCs + 2 LCs (either κ or λ)
• IgG, E, D exist as single monomer; whereas, IgA exist as a dimer and IgM as a pentamer.
• IgG has 4 subclasses (IgG1-4) and IgA has 2 subclasses (IgA1-2).
• Free LCs (either κ or λ) and free HCs (either γ, ε, δ, α, or μ) are incomplete Igs that can be detected in the blood at high concentration, which might suggest certain underlying pathological processes.

• Hypogammaglobulinemia is classified into panhypogammaglobulinemia and selective hypogammaglobulinemia.
   Panhypogammaglobulinemia: a decrease in most, if not all, Ig isotypes-- either caused by a primary disorder (hereditary condition wherein Ig production is impaired) or an acquired condition such as protein loss (via renal tubule, GI tract, or lymph channels) or drug-mediated Ig destruction
   Selective hypogammaglobulinemia: a decrease in one specific Ig isotype either due to a primary deficiency, a suppresion of its production due to overproduction of other Ig isotype (e.g. hyper-IgM syndrome causing IgG, IgA, and IgE deficiencies), or an increased consumption in enhanced immune activity (e.g. IgG deficiency in chronic infection and autoimmune disorders)
• Hypergammaglobulinemia is a common cause of hyperproteinemia and it can be a manifestation of either a monoclonal or polyclonal gammopathy.
   Monoclonal gammopathy:
   Polyclonal gammopathy: