Taral P Parikh 
MD, DNB Rheumatology
Consultant Rheumatologist, Zydus Hospital/ Rheumacare Clinic,
Ahmedabad

Study in focus 1: Proteomic and genomic profiling of plasma exosomes from patients with Ankylosing spondylitis (AS)¹.

Study Synopsis

The pathogenesis of ankylosing spondylitis is evolving. The ability of exosomes to transport miRNAs across cells and alter the phenotype of recipient cells has implicated exosomes in perpetuating inflammation in AS. This study reports the first proteomic and miRNA profiling of plasma-derived exosomes in AS using comprehensive computational biology analysis. Altered expression of genes, microRNAs (miRNAs) or proteins may contribute to immune dysregulation and may play a significant role in the onset and persistence of inflammation in AS.

The study demonstrated that in AS exosomes marker protein CD 63 and CD 81 were higher than controls. AS exosomes cultured with CD 4 T cells showed up-regulation of IFN α2 and Il 33 and cytokine profiling showed down regulation of IL 10 and IL 18. CD 4 T cells in controls in presence of AS exosomes reduced proliferation of FOX P 3 +T Reg cells. This inhibitory effect of AS exosomes suggests their role in inciting prolonged activated state of T cells in AS, thus suggesting a new avenue for treatment target in AS.

Study in focus 2: Myelomonocytic cells in giant cell arteritis (GCA) activate trained immunity programs sustaining inflammation and cytokine production².

Study Synopsis

Multiple cell types are involved in the pathogenesis of GCA. This study looks at the role of monocytic lineage. Trained immunity is a de facto memory program of innate immune cells leading to immunometabolic activation and epigenetic changes leading to increased cytokine production.

Monocytes from GCA patients were subjected to functional studies and metabolic activation was studied using FDG PET and immunohistochemistry. GCA monocytes showed hallmark of trained immunity, increased IL 6 production, increased glycolysis, and epigenetic changes, leading to activation of pro inflammatory genes. The role of this immunometabolism pathway was confirmed using pharmacologic inhibition of GCA monocytes. This pathway sheds light on specific cell type in sustaining inflammation in GCA and target for treatment.

References:

1. Tavasolian F, Lively S, Pastrello C, et al. Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis [published correction appears in Ann Rheum Dis. 2024 Feb 15;83(3):e10]. Ann Rheum Dis. 2023;82(11):1429-1443.
2. Cantoni E, Merelli I, Stefanoni D, et al. Myelomonocytic cells in giant cell arteritis activate trained immunity programs sustaining inflammation and cytokine production. Rheumatology (Oxford). 2023;62(10):3469-3479.