Glucocorticoid gene signatures in systemic lupus erythematosus and the effects of type I interferon: a cross-sectional and in-vitro study

AbstractObjectivesAnti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE). Recently, an association of these autoantibodies with severe COVID-19 was reported in the general population. We assessed whether having pre-existing anti-IFNα autoantibodies was associated with COVID-19 infection in SLE patients.MethodsPatients with SLE who developed COVID-19 between April 1st to October 1st, 2020 were studied. Biobanked pre-COVID-19 plasma from these SLE subjects and healthy controls were tested for anti-IFNα IgG autoantibodies by ELISA. The ability of plasma anti-IFNα autoantibodies to block signal transducer and activator of transcription 1 (STAT1) phosphorylation by recombinant human IFNα in vitro was assessed by flow cytometry.ResultsTen SLE subjects with COVID-19 were identified. A 40% of these subjects had stable autoantibodies against IFNα for up to three years preceding COVID-19 diagnosis. A 50% of the subjects with these autoantibodies neutralized IFNα induced STAT1 phosphorylation.None of the other SLE samples blocked IFNα signaling.ConclusionsWe noted an increased prevalence of pre-existing anti-IFNα autoantibodies in SLE patients with COVID-19 compared to the reported prevalence in lupus patients and the general population with severe COVID-19. Autoantibodies against IFNα in SLE patients may be pathogenic and patients with them maybe at-risk of developing COVID-19.Key MessagesWhat is already known about this subject?-Anti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE) and have recently been associated with severe COVID-19 in the general population.What does this study add?-SLE subjects with COVID-19 had an increased prevalence of pre-existing anti-IFNα autoantibodies compared to the reported prevalence in lupus patients and the general population with severe COVID-19.-Plasma from 50% of subjects with these autoantibodies were able to block in vitro activity of IFNα.-SLE patients with pre-existing anti-IFNα autoantibodies had more severe COVID-19 manifestations.How might this impact on clinical practice or future developments?-Anti-IFNα autoantibodies may be pathogenic and could prove to be a helpful prognostic marker to predict which SLE patient may develop COVID-19 and inform preventive measures and management of this subset of patients.

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Octreotide for the treatment of systemic lupus erythematosus: Clinical effects and an in vitro study on its therapeutic mechanism

Lupus ◽

10.1177/0961203311409268 ◽

2011 ◽

Vol 20 (11) ◽

pp. 1172-1181 ◽

Cited By ~ 2

Author(s):

Y Zhang ◽

W Huang ◽

F Li ◽

S Feng ◽

K Kang ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

In Vitro Study ◽

Vitro Study ◽

Clinical Effects ◽

Systemic Lupus ◽

Therapeutic Mechanism

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Bryophyllum pinnatum leaves ethanol extract inhibit maturation and promote apoptosis of systemic lupus erythematosus BALB/c mice B cells

Medical Journal of Indonesia ◽

10.13181/mji.v26i4.1899 ◽

2018 ◽

Vol 26 (4) ◽

pp. 253-60

Author(s):

Kusworini Handono ◽

Tri W.I. Dantara ◽

Elvira S. Dewi ◽

Mirza Z. Pratama ◽

Nurdiana Nurdiana

Keyword(s):

Systemic Lupus Erythematosus ◽

Flow Cytometry ◽

B Cells ◽

Lupus Erythematosus ◽

In Vitro Study ◽

Ethanol Extract ◽

Vitro Study ◽

Systemic Lupus ◽

Bryophyllum Pinnatum

Background: B cells play a key role in systemic lupus erythematosus (SLE). Targeting B cells as SLE therapy is a plausible approach. This study investigated the potential effects of Bryophyllum pinnatum leaves with ethanol extract in decreasing percentages of maturation, increasing percentages of apoptosis, and decreasing NF-κB p65 expressions of SLE BALB/c mice B cells.Methods: Culturing B cells from pristane induced SLE BALB/c mice’s spleen will resulted in this in vitro study. B cells were activated by BAFF, LPS, IL-4, and anti-CD40 yielding CD19+ >80%. B cells were cultured by adding those stimulants with and without B. pinnatum leaves (0, 0.02, 0.1, or 0.5 µg/ml) for 72 hours at 37°C. Flow cytometry was performed to determine The Percentages of maturation (CD19+CD38+) and apoptosis (Annexin V+PI+) of B cells. Further analysis to determine the expressions of transcription factor of maturation and apoptosis of B cells, NF-ĸB p65, were performed using immunocytochemistry. Data were analyzed using SPSS version 22.Results: Flow cytometry assay showed significant decrease in percentages of maturation of B cells in all doses and significant increase in percentage of apoptosis of B cells in dose 0.5 µg/ml. Immunocytochemistry results showed significant decrease expressions of NF-ĸB p65 in all doses. Percentages of maturation, apoptosis, and expressions of NF-ĸB p65 of B cells were significantly correlated.Conclusion: This in vitro study revealed that B. pinnatum leaves with ethanol extract decreased the percentages of maturation, increased the percentage of apoptosis, and decreased NF-κB p65 expressions of SLE BALB/c mice B cells significantly.

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