Properdin deficiency and meningococcal disease—identifying those most at risk

The complement system plays an important role in host defence against a variety of microorganisms and also makes a crucial contribution to the generation of humoral immune responses. Over the past 30 years a wide variety of inherited complement deficiency states have been described and careful evaluation of these deficiencies has contributed not only to an understanding of the physiological function of the individual components but also to a more general appreciation of the functions of the affected complement pathway. Properdin is a soluble glycoprotein which has a unique role as a positive regulator of the alternative complement pathway by binding and stabilizing the inherently labile C3/C5 convertase enzymes, C3bBb and C3bBbC3b, substantially increasing their half-lives. Properdin, found in plasma at a concentration of about 5-15 mu g/ml, comprises a mixture of oligomers of a 53-kD monomer, mainly dimers, trimers and tetramers in a ratio of approximately 1:2:1, with functional activity increasing with the size of the oligomer. Properdin deficiency was first described in a Swedish family in 1982 in association with fulminant meningococcal disease. Subsequently, over 100 individuals have been described in about 30 kindreds and three distinct variants of properdin deficiency identified. Type I deficiency is characterized by the absence of detectable protein in plasma, type II by the presence of low but detectable plasma properdin (< 10% of normal) and the rare type III by a normal serum concentration of a dysfunctional variant of properdin.