Abstract
Objective:
To study the association of serum IFNα2 levels measured by ultrasensitive single-molecule array (Simoa) and interferon type I gene signature (IGS) with disease activity and determine whether these assays can mark disease activity states in a longitudinal cohort of childhood-onset SLE patients.
Methods:
Serum IFNα2 levels were measured in 338 samples from 48 cSLE patients and 67 healthy controls using IFNα Simoa assay. Five gene IGS was measured by RT-PCR in paired whole blood samples. Disease activity was measured by clinical SELENA-SLEDAI and BILAG-2004. Low disease activity was defined by Low Lupus Disease Activity State (LLDAS) and flares were characterized by SELENA-SLEDAI flare index. Analysis was performed using linear mixed models.
Results:
A clear positive correlation was present between serum IFNα2 levels and the IGS (r = 0.78, p < 0.0001). Serum IFNα2 levels and IGS showed the same significant negative trend in the first three years after diagnosis. In this timeframe, mean baseline serum IFNα2 levels decreased with 55.1% (Δ 201 fg/mL, p < 0.001) to a mean value of 164 fg/mL, which was below the calculated threshold of 219.4 fg/mL, which discriminated between patients and healthy controls. In the linear mixed model, serum IFNα2 levels were significantly associated with both cSELENA-SLEDAI and BILAG-2004, while the IGS did not show this association. Both IFN-I assays were able to characterize LLDAS and disease flare in ROC analysis.
Conclusions:
Serum IFNα2 levels measured by Simoa technology are associated with disease activity scores and characterize disease activity states in cSLE.
To study the association of serum IFNα2 levels measured by ultrasensitive single-molecule array (Simoa) and interferon type I gene signature (IGS) with disease activity and determine whether these assays can mark disease activity states in a longitudinal cohort of childhood-onset SLE patients.
Methods:
Serum IFNα2 levels were measured in 338 samples from 48 cSLE patients and 67 healthy controls using IFNα Simoa assay. Five gene IGS was measured by RT-PCR in paired whole blood samples. Disease activity was measured by clinical SELENA-SLEDAI and BILAG-2004. Low disease activity was defined by Low Lupus Disease Activity State (LLDAS) and flares were characterized by SELENA-SLEDAI flare index. Analysis was performed using linear mixed models.
Results:
A clear positive correlation was present between serum IFNα2 levels and the IGS (r = 0.78, p < 0.0001). Serum IFNα2 levels and IGS showed the same significant negative trend in the first three years after diagnosis. In this timeframe, mean baseline serum IFNα2 levels decreased with 55.1% (Δ 201 fg/mL, p < 0.001) to a mean value of 164 fg/mL, which was below the calculated threshold of 219.4 fg/mL, which discriminated between patients and healthy controls. In the linear mixed model, serum IFNα2 levels were significantly associated with both cSELENA-SLEDAI and BILAG-2004, while the IGS did not show this association. Both IFN-I assays were able to characterize LLDAS and disease flare in ROC analysis.
Conclusions:
Serum IFNα2 levels measured by Simoa technology are associated with disease activity scores and characterize disease activity states in cSLE.
| Original language | English |
|---|---|
| Pages (from-to) | 2872-2879 |
| Number of pages | 8 |
| Journal | Rheumatology |
| Volume | 62 |
| Issue number | 8 |
| Early online date | 14 Dec 2022 |
| DOIs | |
| Publication status | Published - 1 Aug 2023 |
Bibliographical note
Funding Information:This work was made possible by the support of the Sophia Children’s Hospital Fund [B18-04], NVLE (Dutch patient organization for Lupus, APS, Scleroderma and MCTD) [BP12-1-261] and Dutch Arthritis Society [CO-19-001]. The research was performed within the framework of the Erasmus Postgraduate School Molecular Medicine. N.M.I. received financial support from the State Ministry of Baden-Wuerttemberg for Economic Affairs, Labour and Tourism.
Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology.