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Properties of a low molecular weight complement component C6 found in human subjects with subtotal C6 deficiency
A Orren1, R Würzner, P C Potter
1Molecular Immunopathology Unit, MRC Centre, Cambridge, U.K.
Insights
Subtotal C6 deficiency (C6SD) involves low but functional complement component C6. This study suggests C6SD and combined C6/C7 deficiency share an abnormal C6 protein, potentially offering protection against meningococcal disease.
Area of Science:
- Immunology
- Complement System Biology
Background:
- Complement component C6 (C6) is crucial for the terminal complement pathway.
- C6 deficiency can be complete (C6Q0) or partial (C6SD).
Purpose of the Study:
- To characterize C6 in individuals with subtotal C6 deficiency (C6SD).
- To compare C6 in C6SD with C6 in combined C6/C7 deficiency.
Main Methods:
- Quantitation of serum C6 using a sensitive ELISA assay.
- Analysis of C6 properties including molecular weight and isoelectric focusing (IEF).
Main Results:
- Identified C6 levels between 0.3-3 µg/ml as C6SD.
- C6 in C6SD subjects was haemolytically active with reduced molecular weight (approx. 86% of normal).
- IEF analysis revealed an identical abnormal C6 band pattern in C6SD and combined deficient subjects.
Conclusions:
- The abnormal C6 protein in C6SD subjects appears identical to that in combined C6/C7 deficient subjects.
- Low C6 levels may confer protection against meningococcal disease.
Abstract:
A sensitive ELISA assay was used to quantitate serum complement component C6 concentrations. Levels in the range 0.3-3 micrograms/ml were measured in samples from eight individuals (four separate pedigrees) and two subjects with subtotal combined C6/C7 deficiency who have been reported previously. We defined C6 levels in this range as subtotal C6 deficiency (C6SD). In contrast, C6 deficiency with levels below 0.03 micrograms/ml was defined as C6Q0. C6Q0 has been found in 29 unrelated cases which have already been reported. Investigations of the properties of the C6 found in the C6SD subjects showed it to be haemolytically active and able to incorporate into the terminal complement complex. The protein had a relative molecular weight (Mr) of approximately 86% of normal C6 and this Mr was identical to that of the C6 of one combined deficient subject. The Mr of the C6 of the other combined deficient subject was previously estimated as 79% of the Mr of normal C6. Isoelectric focusing (IEF) analysis with band development by haemolytic overlay revealed that all C6SD samples produced an identical weak C6 band pattern anodal to normal C6A bands. The C7 IEF patterns of the two combined deficient subjects were identical, and the C6 IEF patterns of both were identical to those of the C6SD subjects. Thus the C6 of the combined deficient subjects is probably the same abnormal protein found in the C6SD individuals. None of the C6SD or combined deficient subjects have had meningococcal disease and it may be that low C6 levels afford some protection.