4.5 Article

Effect of exogenous IL-37 on immune cells from a patient carrying a potential IL37 loss-of-function variant: A case study

Journal

CYTOKINE
Volume 162, Issue -, Pages -

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2022.156102

Keywords

Interleukin 37; Rare genetic variant; Autoimmune diseases; Inflammation; Case study

Ask authors/readers for more resources

A case study was conducted on a patient with a heterozygous stop-gain variant in the IL37 gene, which did not result in a clear pro-inflammatory phenotype in immune cells.
Introduction: Chronic inflammatory or autoimmune diseases are commonly treated with immunosuppressive medication such as NSAIDs, corticosteroids, or antibodies against specific cytokines (TNF, IL-1 IL-17, IL-23, etc.) or signalling cascades (e.g. JAK-STAT inhibitors). Using sequencing data to locate genetic mutations in relevant genes allows the identification of alternative targets in a patient-tailored therapy setting. Interleukin (IL)-37 is an anti-inflammatory cytokine with broad effects on innate and adaptive immune cell function. Dysfunctional IL-37 expression or signalling is linked to various autoinflammatory disorders. The administration of recombinant IL37 to hyperinflammatory patients that are non-responsive to standard treatment bears the potential to alleviate symptoms.Methods: In this case study, the (hyper)responsiveness of immune cell subsets was investigated in a single patient with a seronegative autoimmune disorder who carries a heterozygous stop-gain variant in IL37 (IL37 Chr2 (GRCh37):g.113670640G > A NM_014439.3:c.51G > A p.(Trp17*)). As the patient has been non-responsive to blockage of TNF or IL-1 by Etanercept or Anakinra, respectively, additional in-vitro experiments were set out to elucidate whether treatment with recombinant IL-37 could normalise observed immune cell functions.Findings: Characterisation of immune cell function showed no elevated overall production of acute-phase proinflammatory cytokines by patient PBMCs and neutrophils at baseline or upon stimulation. T-cell responses were elevated, as was the metabolic activity and IL-1Ra production of PBMCs at baseline. The identified stop-gain variant in IL37 does not result in the absence of the protein in circulation. In line with this, treatment with recombinant IL-37 did overall not dampen immune responses with the exception of the complete suppression of IL-17.Conclusion: The heterozygous stop-gain variant in IL37 (IL37 NM_014439.3:c.51G > A p.(Trp17*)) is not of functional relevance as we observed no clear pro-inflammatory phenotype in immune cells of a patient carrying this variant.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available