134. The expression of inducible nitric oxide synthase and arginase-1 in patients with IgA vasculitis nephritis
Creators: name: Gordana Laskarin1, 2
name: Kifer3, Nastasia
name: Babarovic2, Emina
name: Sestan3, Mario
name: Held3, Martina
name: Kifer4, Domagoj
name: Frkovic3, Marijan
name: Bulimbasic3, Stela
name: Coric3, Marijana
name: Gagro5, Alenka
name: Jelusic3, Marija
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background</strong>: Macrophages, categorized as M1 (calprotectin+ subtype) or M2 (CD163+ subtype), infiltrate glomerules and tubulointerstitium of the kidney of patients suffering from IgA vasculitis (IgAV). The number of tubulointerstitial CD163+ macrophages predicts chronic kidney failure. Arginase-1 is the marker of all M2 macrophages, and inducible nitric oxide synthase (iNOS) is the marker of all classically activated M1 macrophage. iNOS shows the activity of inflammation when expressed on the epithelial cells of the intestine. However, the role of iNOS in the development of IgAV is still undetermined. Aim of this research was to determine the distribution of CD68+, iNOS+ and arginase 1+ cells in the kidney tissue of patients with IgAV, their quantity in regard to patients' histologic features and finally the interrelation between CD68+ cells CD3+ and CD56+ cells. <strong>Methods:</strong> CD68+, iNOS+ and arginase1+ were marked with immunohistochemical methods while the double staining of iNOS, arginase-1, CD3 or CD56 with CD68 marker was achieved with double immunofluorescence in kidney biopsy samples of 22 patients with IgAV nephritis. Four patohistologic classifications were used in analysis: ISKDC, Haas, Oxford, and SQC classification. <strong>Results:</strong> Number of CD68+ cells is similar in glomeruli [4,6 (2,6; 13,7)] and in tubulointerstitium [3,3 (2; 6,2)], [median (25. i 75. percentiles)]. There was a similar number of arginase-1+ and iNOS+ cells in glomerules, interstitium and tubules. Double-stained CD68+/iNOS+ cells were found in glomerules and tubules, with only a few CD68+/arginaza-1+ cells. Clusters of CD3+ lymphocytes were imprinting on the interstitium, however, less on the glomeruli. They were found near macrophage and tubular epithelia cells. CD56+ lymphocytes were rarely marked, mostly in glomeruli. Classification stages/total classification scores and all histological variables were evaluated for possible correlation with macrophage count. A statistically significant negative correlation was found between segmental glomerulosclerosis (Oxford classification) and arginase-1+ cells and an indication of negative correlations between arginase-1+ cells and segmental sclerosis, as well as adhesions (SQC classification) in the glomeruli. <strong>Conclusions:</strong> Alongside CD68+ macrophages, tubular epithelia cells express CD68 and present an important source of iNOS, enclosed by CD3+ lymphocytes. The interrelationship of iNOS+CD68+ cells and lymphocites is yet to be explored, as well as their relationship with nephritis activity. Infiltration of glomeruli with arginase-1+ cells was highlighted as a possible negative predictor for segmental glomerulosclerosis, which should be further examined. <strong>Disclosures</strong>: Research is supported by Croatian Science Foundation project IP-2019-04-8822 and University of Rijeka research grant No. Uni-ri-biomed-18-110