Primary Immunodeficiency Disorders

Selective IgA deficiency (IgAD) is the most common primary genetic immune defect, with high prevalence in Western countries and relatively low prevalence in the East. The laboratory definition of IgAD is based on the measured serum component. However, the important manifestations of deficiency of IgA, the most prevalent of human antibodies, relate to the absence of secretory IgA, which covers a vast surface area of the human body. Diagnostic criteria by the International Union of Immunological Societies (IUIS) define IgAD as very low or absent levels of IgA (< 0.07 g/L) in a child older than 4 years of age. IgAD is asymptomatic in the majority but if symptoms do occur, these generally manifest with mild infections of the respiratory tract with encapsulated bacteria or intermittent diarrhoea with G.lamblia. Symptomatic patients should be investigated for deficient polysaccharide antibody responses, IgG subclass deficiency or allergies because of increased frequency of these conditions co-existing in these patients. IgAD also increases risk for autoimmunity and malignancies but surveillance guidelines are currently lacking. Treatment of IgAD includes reassurance of the asymptomatic patient, optimal control of allergies, prophylactic antibiotics and very rarely immunoglobulin replacement. INTRODUCTION A estimated 6 million individuals worldwide are affected by Primary Immunodeficiency (PID), also called genetic immunodeficiencies. In Africa alone up to 900 000 people may be living with a PID, most of whom are not recognised.1 The overall prevalence is approximately 1:10,000 live births and this is increased in countries with high consanguinity or genetic isolation. Genetic defects of the immune system usually cause increased susceptibility to infections that are often severe, persistent, unusual, recurring (SPUR), debilitating and sometimes fatal. More recently also autoinflammatory and dysregulatory conditions have been included in the International Union of Immunological Societies (IUIS) classification. Primary antibody deficiencies (PAD) are the most common of the genetic deficiencies of the immune system. Mutations of antibody related genes may result in impaired regulation of B-cell development and maintenance or in the immunoglobulin genes. Characteristic is the inability to produce sufficient functional antibodies for protection against harmful antigens, with onset of symptoms commonly in early childhood, although onset may also occur in adulthood. Typical symptoms of hypoagammaglobulinaemia are those of respiratory infections such as sinusitis, bronchitis and pneumonia although skin infections, gastrointestinal complaints, arthritis and other may be seen also. Autoimmune manifestations and allergies may be features of antibody deficiencies too. Infections are classically caused by encapsulated bacteria, because these require anti-polysaccharide antibodies which do not require T-cell assistance for effective clearance of infection. But patients with antibody deficiencies may also show inability to maintain long-term antiviral immunity despite adequate T-cell control. This is exemplified by the dissemination of poliovirus from the gut and enteroviral encephalitis seen in patients with severe antibody deficiencies such as agammaglobulinaemia. IgAD, the commonest of antibody deficiencies in the Western world, is thought to be present from birth, with the majority of affected people being clinically asymptomatic. True deficiency is defined as serum IgA levels equal to or below 0.07 g/L with normal IgM and IgG levels at age 4 years or older.2 It is important to be aware of different test methodologies and ranges of detectable levels, as some laboratories may not titer out to these low levels. Symptom onset can already be in the first year of life but the physiologic lag in serum IgA production can delay the diagnosis until after age of two. Infections may later disappear with maturity or they may persist throughout life.3 Symptoms are more likely to occur in association with IgG