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H deficiency in two brothers with atypical dense intramembranous deposit disease
Insights
This study identifies a rare H deficiency in two brothers with glomerulonephritis and lung infections, suggesting an autosomal recessive inheritance pattern for this complement system defect.
Area of Science:
- Immunology
- Nephrology
- Genetics
Background:
- H factor deficiency is a rare genetic disorder affecting the complement system.
- Early-onset glomerulonephritis and recurrent lung infections are severe clinical manifestations.
Observation:
- Two Algerian brothers presented with glomerulonephritis and H deficiency, characterized by undetectable CH50/AP50 and low H, C3, and B levels.
- Renal biopsies showed dense intramembranous deposit disease with atypical C3 deposition patterns.
- Autosomal recessive inheritance was suggested by familial H factor levels.
Findings:
- The H deficiency was linked to complement alternative pathway dysregulation and decreased terminal complement components.
- Atypical C3 deposition suggests a role for alternative pathway activators in disease pathogenesis.
- This case highlights a potential link between nephritic factor, complement activation, and dense intramembranous deposit disease.
Implications:
- Understanding H deficiency mechanisms can inform the diagnosis and management of glomerulonephritis.
- This study provides insights into the complex interplay between complement, infection, and kidney disease.
- Further research into alternative pathway regulation may reveal novel therapeutic targets for complement-mediated kidney diseases.
Abstract:
We report an H deficiency in two Algerian brothers who had early-onset glomerulonephritis. In addition, one suffered from serious lung infections. The H deficiency was defined by undetectable CH50 and AP50, and low levels of H, C3 and B (less than 10% of normal levels). I and classical pathway components, including C4-bp were normal. CR1 was present on both patients' erythrocytes. No nephritic factor or other circulating alternative pathway activator was detected. The parents, who are first cousins, and a healthy brother and sister had half-normal levels of H. These findings favor an autosomal recessive transmission of the H defect. Although by electron microscopy renal biopsies from both patients were typical for dense intramembranous deposit disease, immunofluorescence microscopy showed an atypical pattern with abundant granular C3 deposits within the mesangium and along the capillary walls. Alternative pathway activators, possibly related to dense deposits, may allow the formation of membrane-associated C3/C5 convertases, unusually stable in the absence of H, since C5, C6, C7, C8 and C9 levels were decreased in both patients. This observation may represent an interesting clue to the relationship between nephritic factor, alternative pathway activation, and dense intramembranous deposit disease.