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The phenotype of SLE associated with complete deficiency of complement isotype C4A
T R Welch1, C Brickman, N Bishof
1Division of Nephrology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
Insights
Complete deficiency of complement C4A isotype is linked to systemic lupus erythematosus (SLE). C4A-deficient SLE patients showed significantly less renal disease and lower C3 levels, suggesting a milder disease course.
Area of Science:
- Immunogenetics
- Rheumatology
- Complement System Biology
Background:
- Complete deficiency of the complement C4A isotype is a recognized genetic risk factor for systemic lupus erythematosus (SLE).
- The specific clinical and serological disease phenotype associated with C4A deficiency in SLE patients has not been previously defined.
Purpose of the Study:
- To define the disease phenotype of patients with SLE and C4A deficiency.
- To compare the clinical and serological features of C4A-deficient SLE patients with those who are C4A replete.
Main Methods:
- Identification of 18 (9%) C4A-deficient individuals among 200 SLE patients from five centers.
- Comparative analysis of clinical and serological features between C4A-deficient and C4A-replete SLE patient groups.
Main Results:
- C4A-deficient SLE patients exhibited significantly lower rates of renal disease (11% vs. 46%, P < 0.006).
- Lower serum concentrations of complement C3 were observed in C4A-deficient patients (11% vs. 35%, P < 0.04).
- A trend towards milder disease was noted in the C4A-deficient cohort.
Conclusions:
- C4A deficiency in SLE is associated with a distinct phenotype characterized by reduced renal involvement and lower C3 levels.
- The findings suggest that C4A-deficient individuals may experience a milder form of SLE.
- Clinicians should be cautious about aggressive C4 level normalization in these patients due to their inherent deficiency.
Abstract:
Complete deficiency of the complement C4A isotype is a known genetic risk factor for systemic lupus erythematosus (SLE). The disease phenotype of C4A-deficient patients has never been defined. Among 200 patients with SLE from five centers, 18 (9%) with C4A deficiency were identified. These individuals were compared to those who were C4A replete with regard to a series of clinical and serologic features. The only significant differences between the two groups were in the presence of renal disease (C4A deficient, 11%; C4A replete, 46%; P < 0.006) and a decrease in the serum concentrations of C3 (C4A deficient, 11%; C4A replete, 35%; P < 0.04). There was also a trend for the C4A-deficient individuals to have milder disease. In light of the tendency for C4A-deficient individuals to have lower serum concentrations of C4, it is important that such patients not be subjected to overly aggressive efforts to "normalize" their C4 levels.