Navigating the maze of complement genetics: a guide for clinicians.

Genetic deficiencies of nearly all of the 30 complement system proteins have been recognized clinically. In many instances, the molecular basis for the deficiency has been elucidated. As a byproduct of these studies, we now have new insights into the pathophysiologic role of complement studies in several acquired diseases.

Complement: a critical test of its biological importance.

The biological activities of the more than 30 proteins that comprise the complement system have been elucidated in parallel lines of investigation that resulted in the purification of the proteins and studies of their function in vitro. Twenty years ago, the first complement cDNA clones were generated. Subsequently the structure and chromosomal localization of the complement genes and the primary sequences of their gene products were revealed.

Population-based estimates of surfactant protein B deficiency.

Objective: Surfactant protein B deficiency is a lethal cause of respiratory distress in infancy that results most commonly from a homozygous frameshift mutation (121ins2). Using independent clinical ascertainment and molecular methods in different populations, we sought to determine allele frequency.

Study Design: Using clinical characteristics of the phenotype of affected infants, we screened the Missouri linked birth-death database (n = 1 052 544) to ascertain potentially affected infants.

Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B.

In systemic lupus erythematosus, the renal deposition of complement-containing immune complexes initiates an inflammatory cascade resulting in glomerulonephritis. Activation of the classical complement pathway with deposition of C3 is pathogenic in lupus nephritis. Although the alternative complement pathway is activated in lupus nephritis, its role in disease pathogenesis is unknown.

The role of complement activation in tumour necrosis factor-induced lethal hepatitis.

Injection of tumour necrosis factor (TNF) in animals causes severe liver cell toxicity, especially when D-(+)-galactosamine (GalN) is co-administered. After challenge with TNF/GalN, serum complement activity (CH50 and APCH50) decreased dramatically, suggesting strong activation of both the classical and the alternative pathways. TNF or GalN alone had no such effect.