Journal Article

FRI0516 Insight into inflammatory cell and cytokine profiles in adult iga vasculitis

Hočevar, A., Tomšič, M., Lakota, K., Kuret, T., Čučnik, S., Sodin-Šemrl, S., Žigon, P., Ogrič, M.

2018

Overview

BackgroundImmunoglobulin A vasculitis (IgAV) is a small vessel, immune complex vasculitis, involving skin, joints, gastrointestinal tract (GIT) and kidney. While different diagnostic/prognostic and inflammatory markers have already been studied in paediatric IgAV, data on adult cases are scarce1.ObjectivesTo examine the inflammatory cell profile in peripheral blood and cytokine profile in sera of newly diagnosed, biopsy-proven and treatment-naïve adult IgAV compared to healthy blood donors (HBD), and determine associations with IgAV clinical signs.MethodsFlow cytometry of stained, lysed and fixed whole blood was performed in IgAV (n=30), and HBD (n=17) (Miltenyi). Cytokines were quantitated by multiplex bead assay (Luminex), ELISA (IL-6) and immunonephelometry (acute phase serum amyloid A (SAA)) in 57 IgAV vs. 53 HBD.ResultsPercentage of CD16+ neutrophils was significantly higher, while percentages of CD3+ T-cells (including CD4+ and CD8+ cells), as well as CD19+ B-cells were significantly lower in peripheral blood of IgAV patients vs. HBD. The expression of l-selectin (CD62L) on CD16+ neutrophils was significantly increased in IgAV vs. HBD, as were the sera levels of TNF-α (2-fold), IL-6 (3-fold), IL-8 (2.2-fold) and SAA (11.7-fold changed levels) (table 1). Association was found between GIT involvement and lower neutrophil expression of integrin αM (CD11b) (median; IQR: 7.2; 4.2–16.0), compared to skin limited (17.8; 9.9–40.5) IgAV cases (p=0.047). There was no association found between different cytokines and IgAV clinical phenotype.Abstract FRI0516 – Table 1Cell profiles, neutrophil surface proteins and cytokines in IgAV patients compared to HBDMEDIAN (Q25-Q75)MEDIAN (Q25-Q75) Cells(% of WBC)HBD(n=15)IgAV(n=15)P valueCytokines (pg/ml)HBD(n=53)IgAV(n=57)P value Neutrophils51.0(47.1–56.9)67.5(63.6–73.3)<0.001IL-1β0.4(0.4–0.4)0.4(0.4–1.5)ns T-cells26.4(23.0–31.8)16.6(10.2–21.4)<0.001IL-62.0(1.0–6.0)6.0(2.8–14.3)0.015 CD4+T cells13.6(11.7–18.4)10.4(7.7.–14.4)0.003IL-853.3(10.9–195.0)117.1(29.3–443.9)0.018 CD8+T cells10.3(6.0–12.6)5.0(1.9–7,9)0.002IL-919.0(19.0–19.0)19.0(19.0–19.0)ns B-cells3.8(2.9–4.7)2.4(1.6–2.9)0.006IL-101.0(0.8–2.8)0.04(0.04–1.3)ns NK cells4.6(3.8–6.3)3.6(2.3–6.1)nsIL-13665.2(354.1–1668.0)23.0(23.0–102.2)ns Neutrophil surface proteins (MFI)HBD(n=17)IgAV(n=30)IL-231.4(1.4–82.9)1.4(1.4–118.6)ns CD62L56.4(44.9–73.7)86.5(45.4–107.5)0.036TNF-α3.9(0.8–15.5)8.1(3.0–20.2)0.003 CD11b8.7(5.5–27.4)15.7(6.4–31.3)nsSAA (μg/ml)2.8(1.9–4.7)32.8(7.2–168.0)<0.001 ConclusionsWe found significant up-regulation of neutrophils and their CD62L expression, as well as sera levels of IL-6, IL-8, TNF-α and SAA in IgAV, implying a pathogenic role of neutrophils in IgAV. CD11b might represent a promising surface marker of GIT involvement in adult IgAV.Reference[1] Nagy GE, Kemény L, Bata-Csörgő Z, et al. Neutrophil-to-lymphocyte ratio: A biomarker for predicting systemic involvement in adult IgA vasculitis patients. J Eur Acad Dermatol Venereol2017;31(6):1033–1037.AcknowledgementsThe authors would like to thank the Rotary club Zgornji Brnik, Slovenia, as well as Prof. Mauro Peretti and Dr. Suchita Nadkarni from WHRI, Queen Mary, University of London for their support. We would also like to thank the Sovenian Research Agency for financial support.Disclosure of InterestNone declared

• Publisher: Elsevier Limited
• Subject: Amyloid / Biopsy / Blood & organ donations / Blood donors / CD11b antigen / CD16 antigen / CD19 antigen / CD3 antigen / CD4 antigen / CD8 antigen / Cytokines / Gastrointestinal tract / Immunoglobulin A / Inflammation / Interleukin 10 / Interleukin 13 / Interleukin 6 / Interleukin 8 / Interleukin 9 / Joint diseases / L-selectin / Lymphocytes B / Neutrophils / Patients / Phenotypes / Skin / Surface markers / Vasculitis