Can Annexin A1 Expression on Neutrophils Distinguish Adult IgA Vasculitis from Other Small Vessel Vasculitides?

Tadeja Kuret¹, Katja Lakota^1,2, Polona Žigon¹, Manca Ogrič¹, Boris Lestan¹, Snezna Sodin Semrl^1,2, Saša Čučnik^1,3, Matija Tomšič^1,4 and Alojzija Hočevar¹, ¹Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia, ²Faculty of Mathematics, Natural Science and Information Technology, University of Primorska, Koper, Slovenia, ³Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia, ⁴University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Annexins, Immunoglobulin (IG), neutrophils and vasculitis

Session Information

Date: Tuesday, November 7, 2017

Title: Vasculitis Poster III: Other Vasculitis Syndromes

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Immunoglobulin A vasculitis (IgAV, formerly Henoch–Schönlein purpura) is a small vessel, immune complex vasculitis characterized by dominant IgA deposits in the vascular wall. Clinical symptoms include skin, joint, gastrointestinal (GI) or renal involvement. Adults frequently develop more severe disease than children¹. Recently, the neutrophil to lymphocyte ratio (NLR) has been proposed as a potential marker for predicting systemic involvement in adult IgAV². Moreover, neutrophil phenotypes have been shown to be differentially involved in disease progression of other vasculitides³. We aimed to determine the percentage of neutrophils, T- and B-cells, NLR and mean fluorescence intensity (MFI) of CD62L and Annexin A1 (AnxA1) on CD16⁺ neutrophils in peripheral blood of newly diagnosed, biopsy-proven adult patients with IgAV compared to other small vessel vasculitides (non-IgAV) and healthy blood donors (HBD).

Methods: Flow cytometry of stained, lysed and fixed whole blood was performed in IgAV (n=15; n=9 for AnxA1), non-IgAV patients (n=11; n=6 for AnxA1) and HBD (n=16; n=7 for AnxA1). The diagnoses of non-IgAV included infection-associated small vessel vasculitis, vasculitis associated with tubulointerstitial nephritis and uveitis, ANCA vasculitis and, cryoglobulinemic vasculitis. IgAV patients were further divided into two groups based on organ involvement (patients with isolated skin involvement; n=9 and patients with concomitant renal or GI involvement; n=6). In the IgAV group only one patient had concomitant infection (of urinary tract).

Results: Percentage of CD16⁺ neutrophils and NLR were significantly higher, while percentages of T- (CD3⁺) and B-cells (CD19⁺) were significantly lower in newly diagnosed IgAV and non-IgAV cases compared to HBD. Expression of AnxA1 was significantly elevated on CD16⁺ neutrophils in IgAV (16.1 (12.9-19.4); median (IQR)) compared to non-IgAV (10.0 (8.1-15.2); p=0.029 (Table 1)). IgAV patients with skin and renal or GI involvement had a significantly higher percentage of CD16⁺ neutrophils (77.1 (67.2-83.6)) compared to skin limited IgAV cases (64.5 (57.1-69.1); p=0.012).

Table 1: Neutrophil/Lymphocyte percentages, their ratio and expression of AnxA1 and CD62L in IgAV patients as compared to HBD and non-IgAV patients
	MEDIAN (IQR)			P VALUE
	HBD	IgAV	Non-IgAV	HBD vs. IgAV	HBD vs. non-IgAV	IgAV vs. non-IgAV
Neutrophils (%)	51.0 (47.1-56.9)	67.5 (63.6-73.3)	69.0 (59.4-78.2)	<0.0001	<0.0001	0.9586
T-cells (%)	26.4 (23.0-31.8)	16.6 (10.2-21.4)	17.8 (19.2-21.4)	0.0004	0.0096	0.8355
B-cells (%)	3.8 (2.9-4.7)	2.4 (1.6-2.9)	1.5 (0.9-2.7)	0.0042	0.0083	0.3502
NLR	1.7 (1.4-2.1)	3.3 (2.8-5.8)	3.4 (2.2-7.1)	0.0001	0.0043	0.8967
Annexin A1 (MFI)	21.3 (18.4-23.7)	16.1 (12.9-19.4)	10.0 (8.1-15.2)	0.0549	0.0023	0.0290
CD62L (MFI)	56.4 (44.9-72.0)	83.7 (58.6-102.8)	92.2 (61.0-127.1)	0.0575	0.0256	0.4743

Conclusion: Our study reports that neutrophil AnxA1 might represent a good surface marker for distinguishing IgAV from other small vessel vasculitides.

References:

Jennette JC, Falk RJ, Bacon PA. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65:1-11.
Nagy GE, Kemény L, Bata-Csörgő Z. Neutrophil-to-lymphocyte ratio: A biomarker for predicting systemic involvement in adult IgA vasculitis patients [published online Feb 21 2017]. J Eur Acad Dermatol Venereol. 2017. doi: 10.1111/jdv.14176. 2017.
Nadkarni S et al. Investigational analysis reveals a potential role for neutrophils in GCA disease progression. Circ. Res. 2014;114:242-48.

Disclosure: T. Kuret, None; K. Lakota, None; P. Žigon, None; M. Ogrič, None; B. Lestan, None; S. Sodin Semrl, None; S. Čučnik, None; M. Tomšič, None; A. Hočevar, None.

To cite this abstract in AMA style:

Kuret T, Lakota K, Žigon P, Ogrič M, Lestan B, Sodin Semrl S, Čučnik S, Tomšič M, Hočevar A. Can Annexin A1 Expression on Neutrophils Distinguish Adult IgA Vasculitis from Other Small Vessel Vasculitides? [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/can-annexin-a1-expression-on-neutrophils-distinguish-adult-iga-vasculitis-from-other-small-vessel-vasculitides/. Accessed .

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/can-annexin-a1-expression-on-neutrophils-distinguish-adult-iga-vasculitis-from-other-small-vessel-vasculitides/