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Neutrophil MiRNA-128-3p is Decreased During Active Phase of Granulo-matosis with Polyangiitis
Marcin Surmiak1, Magdalena Hubalewska-Mazgaj1, Katarzyna Wawrzycka-Adamczyk1
1Department of Internal Medicine Jagiellonian University Medical CollegeKrakow, Poland.
Abstract:
Granulomatosis with polyangiitis is a rare chronic inflammatory disease. In this multisystem autoimmune disorder neutrophils cause small vessels necrosis and infiltrate perivascular tissue to form granulomas. Progression of the disease is evaluated by the symptoms score and by a titer of anti-neutrophil cytoplasm antibodies. Despite glucocorticoid and immunosuppressive therapy, prognosis is complicated by chronic renal insufficiency, hearing loss and skin ulceration. In this preliminary study we tested the hypothesis that altered neutrophil expression of miRNAs can contribute to the cell activation, extracellular traps formation and decreased apoptosis. First we compared a profile of 728 miRNAs expressed in circulating neutrophils of patients with active disease and matched healthy donors. Subsequently, candidate miRNAs were quantified in neutrophils from 16 subjects with active disease, 16 asymptomatic patients at the remission and in 16 healthy controls. Out of 11 candidate miRNAs, only miR-128-3p was both biologically (relative quantity < 30% control or remission patients) and statistically (p<0.01) decreased in the cells during active stage of the disease. This miRNA correlated with a clinical score of the disease well. A set of 10 transcripts involved in the mechanism of the disease was quantified from the same neutrophils RNA. Relative expression of MMP9 was higher in neutrophils from the patients with active disease and correlated negatively with miR-128-3p. The opposite finding was present for MTA1 transcripts. Despite surprisingly scarce changes in the expression of neutrophil miRNAs, miR-128-3p is the best candidate for deciphering etiology of granulomatosis with polyangiitis.
Insights
In granulomatosis with polyangiitis, miR-128-3p is significantly decreased in neutrophils during active disease. This microRNA correlates with disease severity and may offer insights into the autoimmune disorder's etiology.
Area of Science:
- Immunology
- Genetics
- Pathology
Background:
- Granulomatosis with polyangiitis (GPA) is a rare, chronic, multisystem autoimmune disease.
- Neutrophil activation and granuloma formation are key pathological features of GPA.
- Current treatments have limitations, and understanding GPA's etiology is crucial.
Purpose of the Study:
- To investigate the role of altered neutrophil microRNA (miRNA) expression in GPA pathogenesis.
- To identify specific miRNAs contributing to neutrophil activation, extracellular trap formation, and apoptosis in GPA patients.
Main Methods:
- Compared miRNA profiles (728 miRNAs) in neutrophils from active GPA patients and healthy donors.
- Quantified candidate miRNAs in neutrophils from active GPA, remission GPA, and healthy control groups.
- Assessed expression of disease-related transcripts (e.g., MMP9, MTA1) in neutrophils.
Main Results:
- miR-128-3p was significantly decreased (<30% of controls/remission patients, p<0.01) in neutrophils during active GPA.
- Decreased miR-128-3p correlated with clinical disease scores.
- MMP9 expression was elevated and MTA1 expression was reduced in active GPA neutrophils, inversely correlating with miR-128-3p levels.
Conclusions:
- Despite limited overall miRNA expression changes, miR-128-3p is a promising candidate biomarker for GPA.
- Altered miR-128-3p levels in neutrophils may play a role in GPA pathogenesis.
- Further research into miR-128-3p could elucidate GPA etiology and inform therapeutic strategies.
