C1 INHIBITOR FUNCTIONAL DEFICIENCY IN SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE)

C1 inhibitor (C1-inh) was assayed in eight SLE patients presenting wit h consistently low levels of intact C4. C1-inh antigenic levels were n ormal in all patients; however, the function of the C1-inh tested agai nst C1s and C1r was variable and outside the normal functional range i n seven of the eight patients. The molecular weight of patients' C1-in h protein was 105 kD, corresponding to the size of the intact molecule . The C1-inh gene was analysed in all patients. Restriction fragments generated with TaqI, PstI and HgiAI gave no indication of a major C1-i nh gene rearrangement. Direct genomic sequencing of exon VIII revealed three polymorphic point mutations, but there were no changes from the normal gene in or around the reactive-centre residue of C1-inh. Furth ermore, we found no evidence for a C1-inh autoantibody in patients whi ch could affect normal C1-inh function in vitro. These results indicat e that the etiology of C1-inh dysfunction in SLE is heterogeneous and distinct from that reported in either hereditary or acquired angioedem a.