Deficiency of antibodies can be secondary to diseases such as leukaemia which suppress B cell production by the bone marrow or due to loss, especially through the kidneys in conditions such as the nephrotic syndrome. Antibody deficiency is usually secondary to other causes in older patients.
Primary antibody deficiency is usually seen in children and is due to defects in B cells. Antibody deficiency forms a spectrum as regards severity (agammaglobulinaemia means an absence of antibodies, hypogammaglobulinaemia means low levels of antibodies). Some examples are given below:
The hallmark of significant antibody deficiency is recurrent infection. This most commonly affects the respiratory tract and is frequently caused by encapsulated organisms e.g. Streptococcus pneumoniae, Haemophilus influenzae type b. A small number of other organisms can also cause infection in patients with hypogammaglobulinaemia, e.g. diarrhoea caused by Giardia lambia, encephalitis caused by Echo virus.
Treatment of antibody deficiency involves replacing the patient's IgG by regular infusions of this protein (intravenous gammaglobulin) in cases where the IgG level is low and rigorously treating infections with antibiotics.
If a complement component is lacking in an individual the problems encountered depend on which pathway is affected.
Deficiencies of C1, C4 or C2 (classical pathway) are associated with recurrent infections by encapsulated bacteria which require the triad of antibody, complement and neutrophils to respectively bind to, opsonise and phagocytose and kill these bacteria. These patients can instead or in addition suffer from conditions which result from inefficient clearance of immune complexes e.g. glomerulo-nephritis, lupus erythematosus (these are commonly manifest as renal damage, joint problems and rashes). A small number of patients do not appear to experience any disease.
Deficiencies of C3 result in severe problems with recurrent infection and with immune complex mediated disease because of the central position of C3 in the complement pathways.
Deficiencies of alternative pathway components (Properdin, Factor D) are relatively rare. Properdin deficiency is usually associated with a single episode of bacterial meningitis whilst factor D deficiency is commonly associated with recurrent respiratory tract infections.
Despite the potency of the terminal pathway in causing bacterial lysis, deficiencies of C5, C6, C7, C8 and C9 are associated with recurrent infection with only one group of bacteria, Neisseria. Deficient patients commonly present with recurrent meningococcal meningitis.
There is no specific treatment of complement deficiency so immunisations and antibiotics are used to respectively reduce the risk of and treat infections.
Neutropenia means low numbers of neutrophils in the blood and agranulocytosis means an absence of neutrophils.
Primary neutrophil deficiencies are rare and are due to an abnormality, usually inherited, of the neutrophil itself. The problem can affect phagocytosis (e.g. deficiency of an adhesion molecule, CD18/LFA deficiency, on the neutrophil surface) or the metabolic pathways involved in intracellular killing (e.g. in chronic granulomatous disease in which there is an abnormal cytochrome).
Patients with neutrophil defects suffer from recurrent chest infections with bacteria or fungi, recurrent skin abscesses often caused by Staphylococcus aureus and poor wound healing.
Treatment centres around the use of appropriate antibiotics and anti-fungal agents. Interferon gamma helps prevent infection in chronic granulomatous disease.
