Cytokine profile in granulomatosis with polyangiiti

To evaluate cytokines genes expression in peripheral mononuclear blood cells (PBMC) and cytokines blood levels in patients with granulomatosis with polyangiitis (GPA).

Material and methods

We enrolled 60 patients with GPA aged from 18 to 80 years (21 male and 39 female). 22 patients had localized GPA and 38 patients had generalized GPA. There were 32 patients with relapse of GPA and 28 patients with remission of GPA. Cytokines genes expression was studied in blood by reverse transcription polymerase chain reaction (RT-PCR). We evaluated mRNA for the following cytokines: interferon (IFN)-α, IFN-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, tumor necrosis factor (TNF)-α production in PBMC in 57 GPA patients. Сontrol group consisted of 40 healthy volunteers. Production of IFNα, IL-1β, IL-8, IL-18 and TNF-α was studied by ELISA in blood serum in 40 GPA patients.

Results

.Patients with both generalized and localized GPA had statistically significant (p<0,05) activation of IFN-α and IL-8 mRNA and inhibition of IL-12 and TNF-α mRNA as compared with controls. Patients with relapse and remission of GPA had the same changes in cytokines genes expression. There was an activation of IL-18 gene expression in patients with relapse of GPA as compared with controls. IL-8 concentration in patients with relapse of GPA was significantly higher (p<0,01) than in patients with remission of GPA. Concentration of IL-18 in patients with generalized form was significantly higher than in patienths with localized form of GPA.

Conclusion

IL-8 may play a role in GPA relapse development. However, it cannot be used to evaluate activity due to low sensitivity and specificity. IL-18 production was increased almost in a half of examined patients and was associated with the generalization of the disease.

Key words

Cytokines, cytokines genes expression, ELISA, granulomatosis with polyangiitis.