FRI0280 BAFF AND APRIL GENE EXPRESSION IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS
Authors: Saket Jha, Jagdeep Singh, Ranjana Minz, Aadhar Dhooria, Gsrsnk Naidu, Rajiv Kumar, Manish Rathi, Sanjay Jain, Shashi Anand, Aman Sharma
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Neutrophil activation is the central step in the pathogenesis of ANCA associated vasculitis (AAV). Activated neutrophils are an important source of tumor necrosis factor (TNF) ligands involved in the B cell development and survival, namely, B cell activating factor (BAFF) and a proliferating ligand (APRIL)<sup>1</sup>. They have been postulated to have a role in the pathogenesis of AAV but presently there is limited data<sup>2, 3</sup>. <h3>Objectives</h3> To study the expression of BAFF and APRIL genes in patients with AAV and healthy controls and their correlation with disease activity. <h3>Methods</h3> This was a prospective case-control study. Gene expression of BAFF and APRIL was studied in 20 patients of AAV (10 each with active disease and in remission) and 20 healthy age and sex matched controls. Blood samples were collected after taking due consent. Following RNA extraction (QIAamp RNA blood mini kit) and cDNA synthesis ("Thermo Scientific™ RevertAid™ First Strand" cDNA Synthesis Kit), quantitative real time polymerase chain reaction (qRT-PCR) using SYBR Green I Chemistry was carried out to study relative mRNA expression of BAFF and APRIL. β actin (ACTB) a housekeeping gene was taken as a reference gene. <h3>Results</h3> Out of 20 AAV patients 16 were GPA and 4 MPA. Mean age of patients in active (8 GPA and 2 MPA) and remission (8 GPA and 2 MPA) group was 34.5 ± 16.1 and 39.9 ± 16.6 years respectively. The sex distribution in both groups was 1:1. Mean BVASv3, ESR and CRP in active AAV patients were 18.8 ± 8.5, 54 ± 10.8 mm/h and 41.75 (7.07- 402) mg/l respectively. BAFF gene expression was significantly higher in both active AAV group and remission AAV group compared to controls (p &lt; 0.01, Figure 1). The BAFF expression was significantly higher in AAV patients in remission compared to active AAV patients (p=0.008). In contrast, the APRIL expression did not differ between AAV patients and controls (P = 0.829) or between active and inactive AAV patients (p = 0.166). There was no significant correlation of both BAFF and APRIL expression with disease activity markers (ESR, CRP, platelets and BVASv3). Fig 1- X axis shows the patients groups A-0(active), R-1(remission), C-2(control); Y axis shows the log fold change (LFC) of BAFF expression <h3>Conclusion</h3> BAFF gene is significantly expressed in patients with ANCA associated vasculitis. Among AAV patients there is significantly higher expression of BAFF in patients with inactive disease than active disease. There is no significant APRIL gene expression in patients with AAV. <h3>References</h3> [1] Mackay F, Schneider P, Rennert P, Browning J. BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003; 21:231–64. [2] Krumbholz M, Specks U, Wick M, Kalled SL, Jenne D, Meinl E. BAFF is elevated in serum of patients with Wegener's granulomatosis. J Autoimmun. 2005; 25:298–302. [3] Schneeweis C, Rafalowicz M, Feist E, Buttgereit F, Rudolph PE, Burmester GR, et al. Increased levels of BLyS and sVCAM-1 in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV) Clin Exp Rheumatol. 2010; 28:62–6. <h3>Disclosure of Interests</h3> None declared