Inherited deficiency of the seventh component of complement associated with nephritis. Propensity to formation of C56 and related C7-consuming activity.
A 46-yr-old female with chronic pyelonephritis was found to lack complement (C) activity by the use of hemolytic screen assays in agarose gels. These assays also revealed a propensity of patient serum to form an activated complex of the fifth and sixth components of C, C56. Each of the C component hemolytic activities was present in normal or elevated amounts with the exception of C7, which was undetectable; addition of purified C7 led to the restoration of hemolytic activity. C-dependent phagocytosis, immune adherence, and neutrophil chemotaxis were normal. Family studies demonstrated that the defect was transmitted as an autosomal codominant apparently not linked with alleles at the HLA-A or HLA-B loci. Persisting C56 was readily formed in this as compared to normal serum upon incubation with multiple C activators including zymosan, inulin, immune complexes, heat-aggregated human gamma globulin, endotoxin, and agarose. A heat-stable (56 degrees C, 30 min) activity which consumed C7 with time-and temperature-dependent kinetics was detected in plasma and serum, and seemed to be similar to a "C7 inactivator" previously described in another C7-deficient individual. However, this activity was found to have properties identical to those of C56 during low ionic strength precipitation and chromatography on Sephadex G-200, to be specifically removed upon passage through an anti-C5 immunoadsorbent column, and to be associated with a small amount of C56, suggesting that it represents an expression of small amounts of C56 rather than a new C-inhibitory activity. Thus, an individual with chronic nephritis lacking C7 is reported; the utility of a hemolytic screen assay in agarose plates for the detection of such patients is emphasized; persisting C56 is shown readily to be formed in this serum; and the presence of C7-consuming activity which is associated with and in all likelihood attributable to C56 is shown.
D003182:Complement C5 / Q000378:metabolism*; D003183:Complement C6 / Q000378:metabolism*; D003184:Complement C7 / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006462:Hemolytic Plaque Technique; D006801:Humans; D008875:Middle Aged; D011704:Pyelonephritis / Q000276:immunology*
D003182:Complement C5; D003183:Complement C6; D003184:Complement C7; D006680:HLA Antigens