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Genetically determined low C4: a predisposing factor to autoimmune chronic active hepatitis
Insights
Low C4 levels are common in childhood autoimmune chronic active hepatitis (CAH) and appear to be genetically determined. This suggests a potential link between complement component C4 deficiency and the development of CAH.
Area of Science:
- Immunology
- Genetics
- Hepatology
Background:
- Autoimmune chronic active hepatitis (CAH) is an inflammatory liver disease.
- Complement system deficiencies, particularly C4, are implicated in autoimmune disorders.
Purpose of the Study:
- To investigate the prevalence and potential genetic basis of low C4 serum levels in children with autoimmune CAH.
Main Methods:
- Serum C3 and C4 levels were measured in patients and their families.
- Transferrin, albumin, C3d, and C4d levels were assessed to rule out other causes of low C4.
- C4 phenotyping was performed on patients and parents to identify null allotypes.
Main Results:
- 18 of 26 (69%) pediatric CAH patients had low C4 levels; 5 (19%) had low C3.
- Family studies revealed a higher incidence of low C4 in parents and siblings of affected probands.
- C4 phenotyping showed a significantly higher prevalence of null allotypes in CAH patients (90%) and parents (81%) compared to controls (59%).
Conclusions:
- Low C4 levels in autoimmune CAH are likely genetically determined.
- Defective expression of C4 structural genes may contribute to C4 deficiency and susceptibility to CAH.
Abstract:
Of 26 patients with autoimmune chronic active hepatitis (CAH) starting in childhood 18 (69%) had low C4 and 5 (19%) had low C3 serum levels. Impaired hepatic synthesis and immune-consumption were unlikely since transferrin levels were normal in all patients, albumin levels were persistently low in only 3, and only 3 had raised levels of activation fragment C3d. C4d was normal in all patients studied. In the families of 12 probands with low C4, 7 parents had low C4 and 2 had levels which were at the lower limit of normal. 5 of 10 siblings from 5 families had low C4. These results suggest that low C4 levels in CAH are genetically determined. C4 phenotyping in 20 patients and in 26 parents showed that 90% and 81%, respectively, had null allotypes at either the C4A or C4B locus compared with 59% in controls, indicating that defective expression of structural genes may contribute to the observed C4 deficiency.