Mechanisms in secondary hypogammaglobulinaemia.

Abstract

Hypogammaglobulinaemia refers to the low levels of circulating antibodies associated with a decreased gammaglobulin zone on electrophoresis. Since IgG is the predominant immunoglobulin a deficiency of it will most readily affect the gammaglobulin zone. Deficiencies of IgA and IgM will not necessarily result in a visual decrease in the latter. For practical purposes the clinically important states are the low immunoglobulin levels associated with disease. For IgG, severe hypogammaglobulinaemia is defined as a serum level in an adult of less than 2.0 g/l (MRC Working Party, 1969). At this level 70% of patients suffer severe infection (Hobbs, 1968). During the first six months of life infants commonly have levels below 2-0 g/l, so that in this period 1-0 g/l is better taken as the critical level. If the onset occurs before the age of 3 years (during which time children are building up their memory bank of IgG responses) the residual IgG is poorer in quality than in an adult and infection is much more of a problem. In adults the quality can be so good that down to 1.0 g/l there is no obvious infection, but the usually preceding loss of IgA and IgM can predispose to gut disturbances and malabsorption and loss of weight are common. In some cases primary humoral responses may be affected and infection with organisms not previously encountered may occur long before low levels of immunoglobulins are seen. Hypogammaglobulinaemia may be a result of a longer term inhibition of the humoral immune system, which may be preceded in the early stages by failure to mount a primary response. A normal gammaglobulin level does not necessarily exclude specific humoral response deficiencies (Hobbs, 1966; Hobbs, 1969). The immunoglobulin deficiency can arise from a variety of immunological abnormalities, which may be genetically determined or may be secondary to some other condition. Secondary hypogammaglobulinaemia is 10-100 times more common than the primary forms. In this paper we shall consider clinical conditions which give rise to secondary hypogammaglobulinaemia, with particular reference to the mechanisms producing it. These may be considered under five broad headings (Table 1; Hobbs, 1971).