NONCOORDINATED BIOSYNTHESIS OF EARLY COMPLEMENT COMPONENTS IN A DEFICIENCY OF COMPLEMENT PROTEINS C1R AND C1S

We report on a 60-year-old woman with systemic lupus erythematosus and a total (95%) Clr and a partial (36%) Cls deficiency. The patient complained about cutaneous lesions on forearms and legs without other systemic involvement. Elevated anti-nuclear, anti-native DNA and anti-SSA antibodies were present. The finding of persistently depressed levels of haemolytic complement activity (CH50) on both serum and plasma, associated with normal levels of C3, C4 and C2 components, and normal alternative pathway haemolytic activity showed a deficiency of an early component of the classical pathway. Indeed Clr component was below the limits of detection whereas Cls component was lowered (36%). The depressed CH50 was only corrected by purified Clr. Biosynthesis of Clr and Cls by patient's monocytes was spontaneously normal but not up-regulated by interferon-gamma for Clr alone, whereas the biosynthesis of Cls, but also of interleukin-6, was increased, indicating a specific disregulation of Clr. The deficiency was associated with a lupus syndrome and a fatal assumed septic shock. This is in agreement with other reported cases.