Background/Purpose: Decreases in peripheral blood levels of complement components of C3 and C4 are associated with SLE and often indicate a lupus flare. The aim of this study is to identify the biologic events that underline changes in complement levels and their clinical implications by characterizing peripheral blood features that are associated with low C3 or C4 levels in patients with SLE.

Methods: PBMC samples and multiple clinical and laboratory parameters were collected longitudinally for 71 patients that met ACR criteria for SLE. C3 and C4 were measured by nephelometry (the normal ranges for C3 and C4 were 79–152 mg/dl and 16–38 mg/dl, respectively). Longitudinal PBMC gene expression data were generated by microarray (2-8 visits/patient) for 22 SLE patients from the above group. Based on the data obtained, we built separate statistical models (linear mixed model) for C3 and C4. The relationships of C3 and C4 with the studied parameters were obtained, the p value threshold was set at 0.05 and a multiple testing correction was applied.

Results: C3 and C4 fluctuated during the disease course and from patient to patient. C3 and C4 showed a significant relationship (p<0.05) with each other. Both C3 and C4 correlate positively with serum albumin, alkaline phosphatase and calcium. C3 is positively correlated with WBC, RBC, serum albumin and C-reactive protein, and is negatively correlated with disease activity, as determined by SELENA-SLEDAI or BILAG2004. C3 was lower in patients with high serum creatinine, chloride, proteinurea (by definition of SLEDAI), DNA binding and lymphopenia. Based on longitudinal microarray data, C3 and C4 showed either positive or negative relationships with 1147 transcripts and 37 transcripts, respectively. There were 29 genes correlating with both C3 and C4. The functional analysis of selected transcripts indicates important categories, such as regulation of innate immune response and RNA preprocessing. Transcripts negatively correlating with C3 and C4 include NFATC1, MAP3K8, EGR1 that mediate T cell activation;  or such important molecules as NF1, TNFAIP3, BTG1, DUSP2, CXCR4, NEDD and SHARPIN.

Conclusion: Our data confirmed the usefulness of C3 and C4 for monitoring disease activity in SLE and indicate that C3 might have better prognostic potential than C4. Patients with low C3 tend to have more prominent kidney involvement. Interestingly, C3 showed a better correlation with PBMC gene transcript expression than C4, and low C3 was associated with increased expression of transcripts involved in T cell activation, among other immune activation pathways. The results point to important molecular mechanisms that are associated with SLE disease activity.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/peripheral-blood-and-disease-features-associated-with-complement-components-c3-and-c4-in-sle/