Hypergammaglobulinemia is a rare hereditary medical condition in which the patient has abnormally high levels of gamma globulin. Gamma globulin is a class of proteins found exclusively in the blood and mainly refers to antibodies. In other words, the patient with hypergammaglobulinemia has too many antibodies swimming around in their blood.
In addition to elevated gamma globulin levels, other symptoms of hypergammaglobulinemia include enlarged tonsils, lymph nodes, liver, and spleen; along with anemia; poor immunity; and susceptibility to bacterial and opportunistic infections. With these symptoms, the disease is an immunoproliferative disorder, which means that it greatly weakens the immune system. When the immune system is affected, it makes a person much less able to ward off infection. On top of that, it can even make small infections like the common cold feel much worse.
Causes of hypergammaglobulinemia include a number of diseases, including myeloma, hepatitis C, human immunodeficiency virus 1 (HIV-1), rheumatoid disease, POEMS syndrome, and liver cirrhosis. Treatment of the disease usually includes receiving immune globulin intravenously or taking antibiotics. Many patients, despite treatment, must live with a weakened immune system for the rest of their lives.
Hypergammaglobulinemia presents in five forms, depending on which immunoglobulin is found at abnormal levels. The most common type that people experience is an excess of an immunoglobulin known as IgM. Other types are characterized by a deficiency in the main immunoglobulins IgA, IgE and IgG.
The first and primary type is called hyper IgM type 1, and this is the one with the elevated levels of gamma globulin. The second is a mutation of the activation-induced cysteine deaminase (AICDA) gene found on the short arm of chromosome 12. The third type is also a mutation, this one is found on the surface of B cells. Hyper antibodies IgM type 4 is similar to the first type, but an exact cause has not yet been determined. Hyper IgM type 5 is a mutation of the uracil DNA glycosylase (UNG) gene, which is also located on chromosome 12.
Waldenstrom's macroglobulinemia is a malignant variation of an immunoproliferative immunoglobulin disorder, the category that hypergammaglobulinemia falls into, although it is not considered a form of hypergammaglobulinemia. This condition usually affects people when they are around 55 years old, with a slight predominance towards men. Patients who develop this disorder generally live about six years longer. It is a relatively rare disorder, with only about 1,500 cases annually in the United States; There are around 10.3 incidences per year for every million people living in the UK.