Lupus science & medicine 2018
Erythrocyte-bound C4d in combination with complement and autoantibody status for the monitoring of SLE.
Abstract
Background
We examined the usefulness of erythrocyte-bound C4d (EC4d) to monitor disease activity in SLE.
Methods
Data and blood samples were collected from three different studies, each of which included longitudinal evaluations using the Physicians Global Assessment (PGA) of disease activity and the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI), which was assessed without anti-double-stranded DNA (dsDNA) and low complement C3/C4 (clinical SELENA-SLEDAI). EC4d levels were determined using flow cytometry; other laboratory measures included antibodies to dsDNA, C3 and C4 proteins. Relationships between clinical SELENA-SLEDAI, PGA and the laboratory measures were analysed using linear mixed effect models.
Results
The three studies combined enrolled 124 patients with SLE (mean age 42 years, 97% women, 31% Caucasians and 34% African-Americans) followed for an average of 5 consecutive visits (range 2-13 visits). EC4d levels and low C3/C4 status were significantly associated the clinical SELENA-SLEDAI or PGA in each of the three study groups (p<0.05). Multivariate analysis revealed that EC4d levels (estimate=0.94±0.28) and low complement C3/C4 (estimate=1.24±0.43) were both independently and significantly associated with the clinical SELENA-SLEDAI (p<0.01) and PGA. EC4d levels were also associated with the clinical SELENA-SLEDAI (estimate: 1.20±0.29) and PGA (estimate=0.19±0.04) among patients with chronically low or normal C3/C4 (p<0.01). Anti-dsDNA titres were generally associated with disease activity.
Conclusion
These data support the association of EC4d with disease activity regardless of complement C3/C4 status and its usefulness in monitoring SLE disease. Additional studies will be required to support these validation data.
Related Questions
What is your approach to discordant dsDNA testing, such as positivity to dsDNA by crithidia but negativity to dsDNA by other modalities?
What a great question with many facets. The information I provide is meant to be very practical. These answers are from the viewpoint of a rheumatologist and not an immunologist. I discussed this subject with Dr. Debra Zack, a rheumatologist/immunologist who is an expert with anti-dsDNA, and I had t...
How would you interpret a positive dsDNA in a patient with a negative ANA performed via indirect immunofluorescence?
Another important consideration is the methodology by which the anti-dsDNA antibody was assessed. Most commercial labs use EIA, which is sensitive but not as specific as Farr or Crithidia assays. Many positive EIA results are negative when checked by these more specific methodologies.
How do you approach the use of commercial testing such as AVISE CTD in clinical practice?
Short story to start off with: A little over 20 years ago, I was a young rheumatologist sitting in a meeting room full of more experienced rheumatologists from the Washington DC area. Some of them were very well known in the field. The person in charge asked, "anti-CCP antibodies are now available t...