C1 inhibitor functional deficiency in systemic lupus erythematosus (SLE)

• Published in: Clinical and experimental immunology 1993-05, Vol.92 (2), p.268-273
• Main Authors: JAZWINSKA, E. C., GATENBY, P. A., DUNCKLEY, H., SERJEANTSON, S. W.
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; complement; Complement C1 - analysis; Complement C1 Inactivator Proteins - deficiency; Complement C1 Inactivator Proteins - genetics; Complement C2 - analysis; Complement C4 - analysis; Exons; Genes; Humans; Medical sciences; Molecular Sequence Data; Oligodeoxyribonucleotides - chemistry; polymerase chain reaction direct sequencing; Restriction Mapping; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; systemic lupus erythematosus
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.1993.tb03391.x

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.