C1 inhibitor functional deficiency in systemic lupus erythematosus (SLE)

SUMMARY Cl inhibitor (Cl-inh) was assayed in eight SLE patients presenting with consistently low levels of intact C4. Cl-inh antigenic levels were normal in all patients; however, the function of the Cl-inh tested against C1 s and C1 r was variable and outside the normal functional range in seven of the eight patients. The molecular weight of patients’ Cl-inh protein was 105 kD, corresponding to the size of the intact molecule. The Cl-inh gene was analysed in all patients. Restriction fragments generated with TaqI, PstI and HgiAI gave no indication of a major Cl-inh 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 Cl-inh. Furthermore, we found no evidence for a C1-inh autoantibody in patients which could affect normal Cl-inh function in vitro. These results indicate that the etiology of Cl-inh dysfunction in SLE is heterogeneous and distinct from that reported in either hereditary or acquired angioedema.