C1 inhibitor functional deficiency in systemic lupus erythematosus (SLE). |
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| Authors: | E C Jazwinska P A Gatenby H Dunckley S W Serjeantson |
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| Affiliation: | Human Genetics Group, John Curtin School of Medical Research, Australian National University, Canberra. |
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| Abstract: | C1 inhibitor (C1-inh) was assayed in eight SLE patients presenting with consistently low levels of intact C4. C1-inh antigenic levels were normal in all patients; however, the function of the C1-inh tested against C1s and C1r was variable and outside the normal functional range in seven of the eight patients. The molecular weight of patients' C1-inh 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-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 C1-inh. Furthermore, we found no evidence for a C1-inh autoantibody in patients which could affect normal C1-inh function in vitro. These results indicate that the etiology of C1-inh dysfunction in SLE is heterogeneous and distinct from that reported in either hereditary or acquired angioedema. |
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| Keywords: | complement systemic lupus erythematosus polymerase chain reaction direct sequencing |
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