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Familial partial deficiency of the third component of complement (C3) and the hypocomplementemic cutaneous vasculitis
Insights
Familial C3 deficiency can lead to hypocomplementemic cutaneous vasculitis syndrome. Reduced C3 synthesis predisposes individuals to immune complex-like diseases, highlighting complement
Area of Science:
- Immunology
- Genetics
- Clinical Medicine
Background:
- Familial hypocomplementemia, specifically affecting the third component of complement (C3), presents a rare genetic condition.
- Hypocomplementemic cutaneous vasculitis syndrome (HCVS) and SLE-like syndromes are characterized by immune complex deposition and complement system dysregulation.
Observation:
- A family exhibited familial hypocomplementemia with four affected members.
- The propositus presented with cutaneous vasculitis, hypocomplementemia, arthralgia, proteinuria, and thrombocytopenia, mimicking HCVS or SLE-like syndrome.
- Serum C3 levels were reduced (35-57% of normal) in affected individuals, with negative lupus erythematosus serology.
Findings:
- C3 phenotyping revealed homozygous C3 slow in three hypocomplementemic members and heterozygous C3 fast-slow in one.
- Metabolic studies in a clinically normal mother showed a 50% reduction in C3 synthesis, confirming hypocomplementemia.
- The familial C3 deficiency was linked to the observed immune complex-like disease.
Implications:
- Preexisting C3 deficiency may predispose individuals to immune complex-like diseases such as HCVS.
- Understanding C3 deficiency's role is crucial for diagnosing and managing related autoimmune and vasculitic conditions.
- This study underscores the importance of complement system evaluation in patients with unexplained vasculitis and autoimmune features.
Abstract:
Familial hypocomplementemia of the third component of complement (C3) was found in four members of a family. The prospositus had cutaneous vasculitis, hypocomplementemia, arthralgia, proteinuria and thrombocytopenia. The combination of clinical, laboratory and pathologic findings resembled the "hypocomplementemic cutaneous vasculitis syndrome" (HCVS) or the "SLE-like syndrome" but serum C3 concentration was 35 to 57 per cent of normal in the propositus and in three relatives. Results of Clq precipitins, cryoglobulins and serologic tests for systemic lupus erythematosus were negative. Proteinuria (815 mg/day) but no hematuria was present. Analysis of the C3 phenotypes in this family showed that three hypocomplementemic members were apparent homozygous C3 slow but one was heterozygous C3 fast-slow. Metabolic studies with 125-Iodinated C3 in the clinically normal mother showed a 50 per cent reduction in C3 synthesis which was consistent with hypocomplementemia documented by serum protein assay. The occurrence of an immune complex-like disease (with characteristics of the HCVS) in a patient with a familial deficiency of C3 suggests that the preexisting C3 deficiency may predispose such persons to certain diseases.