Three Distinct Profiles of Serum Complement C4 Proteins in Pediatric Systemic Lupus Erythematosus (SLE) Patients: Tight Associations of Complement C4 and C3 Protein Levels in SLE but not in Healthy Subjects

1. Abstract

The serial changes of serum complement proteins C4 and C3 in SLE were characterized in 33 pediatric SLE patients with defined C4 genotypes. Three distinct groups of C4 protein profiles were observed. The first group was characterized by persistently low C4 levels (<10 mg/dL) throughout the course of the study. Patients with this profile had mild disease manifestations and low to medium copy numbers of C4 genes. The second group featured periodic fluctuations of serum C4 protein concentrations above and below 10 mg/dL, paralleled with ups and downs of SLE disease activities. Most patients with the second profile had unequal copy numbers of C4A and C4B genes and relatively severe disease. The third group had normal serum C4 levels (>15 mg/dL) most of the time and occasionally low C4 and C3 levels that were mostly coincident with disease flares prior to effective medical treatment. Most patients in this group had medium to high C4 gene dosages. In SLE patients but not healthy subjects the serum C3 protein levels were tightly associated with serum C4 protein levels. It was found that a subject’s body mass index (BMI) is an important parameter in determining the serum C3 and C4 levels, both in SLE patients and healthy subjects. However, the BMI is unlikely to be involved in the parallel changes of C3 and C4 in SLE. As expected, the maximum serum C4 concentration present in a patient, which probably reflects the patient’s inherent capacity to produce a physiologic level of C4, was a function of her/his C4 gene dosage. Therefore, classifying C4 and C3 protein profiles and elucidating the genotypic and phenotypic variations of C4 may improve prediction of SLE disease flares and severity, and facilitate more effective management of the disease.