POS0074 CAN WE PREDICT THE DEVELOPMENT OF NEPHRITIS IN PEDIATRIC IGA VASCULITIS PATIENTS?
Authors: E. Sag, S. Demir, Y. Bilginer, S. Özen
Journal: Annals of the Rheumatic Diseases (2021)

Background: IgA vasculitis (IgAV) is the most common systemic vasculitis of childhood, characterized by palpable purpura, arthritis, gastrointestinal and renal involvement 1 . It is a relatively self-limited disease apart from the renal involvement which is associated with the long term morbidity. Objectives: We aimed to define a marker at disease onset to predict the renal involvement. Methods: In this pilot study, we analyzed a targeted panel of vascular inflammation markers (sT2, RAGE, TIE-2, sCD40L, TIE-1, sFlt-1, LIGHT, TNF-a, PlGF, IL6, IL18, IL10 and MCP-1) in the plasma samples of eight patients IgAV at the onset of the disease, before any treatment was initiated. At the time of sample collection, none of the patients had renal involvement; four of these patients subsequently developed nephritis and were defined as the IgAVN group. The levels of the markers were studied by a cytometric bead-based multiplex assay panel according to manufacturer’s instruction (LEGENDplex HU Vascular Inflammation panel 2 (13-plex); catalogue number 740966, Biolegend) and analyzed by Novocyte 3005 flow cytometer. Results: There were no significant differences in gender, age, clinical manifestations, and laboratory findings between IgAV and IgAVN patients (Table 1). sCD40L levels were higher (median 1938.1 vs 754.9 pg/mL, p=0.04) whereas sST2 levels were lower (median 862.8 vs 2302.8 pg/mL, p=0.02) in the patients who developed IgAV nephritis (Figure 1). sRAGE levels were higher and IL18 levels were lower in IgAVN patients but did not reach statistical significance, probably due to the low number of patients. The other parameters did not show any specific pattern. Table 1. IgAV (n=4) IgAVN (n=4) p value Gender 2F, 2M 1F, 3M 0.49 Age at disease onset 9.0±5.4 10.3±3.4 0.68 Arthralgia/arthritis 50% 75% 0.49 GIS involvement 75% 50% 0.49 Haemoglobine (gr/dL) 12.4±2.3 12.3±0.6 0.95 White blood cells, x10 9 /L 11150±1933 8525±1497 0.08 Platelets x10 9 /L 290250±87328 269250±38741 0.68 Erythrocyte sedimentation rate (mm/hr) 10.5±9.1 21.0±14 0.26 C-reactive protein (mg/dL) 0.63±0.03 1.16±0.96 0.39 Data are given as mean±SD Figure 1. Soluble CD40 ligand (sCD40L) is expressed on platelets and released on activation. It is proinflammatory for endothelial cells and promotes coagulation by inducing expression of tissue factor on monocytes and endothelial cells 2 . It was investigated in acute coronary syndrome and was suggested as a risk factor for vascular damage. 2 . Furthermore, the levels of sCD40L were shown to be correlated with disease activity in ANCA-associated vasculitis 3 . Thus in IgAV, sCD40L may be associated with the involvement of the kidney vasculature, which represents the more severe form of the disease. Receptor for advanced glycation end-products (RAGE) is another marker for endothelial damage and vasculitis which was higher in IgAVN, as well. IL33 is expressed by epithelial and endothelial cells and overexpression of IL33 have been shown in large vessel vasculitis 4 . sST2 acts as a decoy receptor and inhibits IL33 signalling 4 . It was interesting to see that the levels of the IL-18 and sST2, which are members of IL-1 family, were lower in IgAVN patients. Conclusion: Although the number of the patients were limited in this pilot study, we suggest that sCD40L and sRAGE might be used to predict the development of renal disease in IgAV patients. Further studies with larger number of patients are needed to confirm our findings. References: [1]Sag E, Batu ED, Ozen S. Childhood systemic vasculitis. Best practice &amp; research Clinical rheumatology 2017;31(4):558-75. [2]Heeschen C, Dimmeler S, Hamm CW, et al. Soluble CD40 ligand in acute coronary syndromes. The New England journal of medicine 2003;348(12):1104-11. [3]Tomasson G, Lavalley M, Tanriverdi K, et al. Relationship between markers of platelet activation and inflammation with disease activity in Wegener’s granulomatosis. The Journal of rheumatology 2011;38(6):1048-54. [4]Desbois AC, Cacoub P, Leroyer AS, et al. Immunomodulatory role of Interleukin-33 in large vessel vasculitis. Sci Rep 2020;10(1):6405. Disclosure of Interests: None declared.