Background/Purpose:

Cell-bound complement activation products, CB-CAPs (C4d deposition on erythrocytes [EC4d], B lymphocytes [BC4d], reticulocytes [RC4d], platelets [PC4d], and C3d deposition on reticulocytes [RC3d]) are sensitive and specific markers for the diagnosis and evaluation of lupus. Cell-specific CB-CAPs may have a role as biomarkers of organ/systems involvement in SLE, such as the association of PC4d with cardiovascular events/presence of antiphospholipid antibodies, and EC4d with proteinuria. The current study investigated the role of CB-CAPs as markers of SLE flares, as well as their possible association with muco-cutaneous involvement.

Methods:

This was a longitudinal study of 33 patients with childhood onset SLE (cSLE, diagnosed at or before age 19) who fulfilled ACR SLE classification criteria and had up to 6 months of follow-up. Venous blood was collected every 3 months for CB-CAPs and results were reported as net mean fluorescence intensity index (MFI). Additionally, anti-dsDNA, complement levels (C3 and C4) and laboratory work needed for SLE Disease Activity Index (SLEDAI) scoring were also evaluated. Disease activity was assessed at each visit using SLEDAI. Lupus flares were identified using the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) SLEDAI flare index (SFI).

Results:

The study included 33 patients (19±4 years old, 79% female, 45% Hispanic, 33% African American). Patients met on average 5±1 ACR-SLE classification criteria; 97% had positive ANA titers, 88% had elevated dsDNA titers, and 21% tested positive for the antiphospholipid antibodies. Abnormal EC4d (>14 net MFI) levels were observed in 19, BC4d (>75 net MFI) in 20, and PC4d levels (> 20 net MFI) in 12 patients. All patients were treated with hydroxychloroquine, 55% with corticosteroids and 70% with immune-suppressants.

Twelve visits with SLE flares were identified, 7 of which were mild/moderate and 5 severe. Of these 12 flares, 5 patients had rashes, 4 arthritis, 4 nephritis (proteinuria) and 1 vasculitis.

SLE patients with flares (SLEDAI = 9 ± 3), as compared to SLE patients with stable disease (SLEDAI = 4 ± 3), had significantly higher PC4d values (18 [IQ 7-70] vs. 8 [IQ 3-15] net MFI; p=0.045). Among these patients with flares, two patients had normal complement levels and another one had stable/normal dsDNA levels but elevated PC4d. EC4d levels were numerically higher in patients with flares, 17 [IQ 14-29] vs 10 [IQ 6-26] net MFI, p=0.07. BC4d was not significantly different between the two groups, 81 [IQ 32-180] vs 77 [IQ 36-135] net MFI, p=0.91. In addition, within the cohort of 33 patients, 14 with rash had elevated RC3d and a trend toward elevated PC4d levels, with a median level of 4 [IQ 1-7] vs. 1 net MFI [IQ 1-4] (p=0.04) and 10 [IQ 5-36] vs. 8 [IQ 3-15] net MFI (p=0.09) respectively.

Conclusion:

These pilot findings suggest CB-CAPs as a potential biomarker to identify disease flares more consistently than low complement or high levels of anti-dsDNA in cSLE. The relatively shorter lifespan of platelets might allow for closer tracking of changes in disease activity associated with flare. Our data also suggest that reticulocyte bound CB-CAPs may play a role as a biomarker to predict muco-cutaneous involvement in cSLE patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cell-bound-complement-activation-products-as-markers-of-disease-flares-in-childhood-onset-systemic-lupus-erythematosus/