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THU0376 Potential Role of Interleukin 32 in Lupus Nephritis Pathogenesis
  1. S. Truglia1,
  2. C. Alessandri1,
  3. F. Ciccia2,
  4. A. Rizzo3,
  5. T. Colasanti1,
  6. F. Miranda1,
  7. F.R. Spinelli1,
  8. F. Ceccarelli1,
  9. G. Triolo2,
  10. G. Valesini1,
  11. F. Conti1
  1. 1Dipartimento di Medicina Interna e Specialità Mediche, Policlinico Umberto I, Sapienza Università di Roma, Rome
  2. 2Dipartimento di Medicina Interna, Divisione di Reumatologia, Palermo
  3. 3Ospedali Riuniti Villa Sofia-Cervello, Palermo, Palermo, Italy

Abstract

Background Lupus nephritis (LN) affects up to 70% of patients with systemic lupus erythematosus (SLE) and is a major cause of morbidity and mortality. There is compelling evidence demonstrating that resident renal cells can directly contribute to renal inflammation through their ability to secrete cytokines, chemokines, and glycosaminoglycans. Interleukin 32 (IL32) is a recently described cytokine with an important role in both innate and adaptive immune responses. IL32 exhibits several properties typical of proinflammatory cytokines by inducing the maturation and activation of dendritic cells, resulting in Th1 and Th17 polarization, and endothelial activation. In addition, overexpression of intracellular IL32 aggravated the secretion of interstitial collagenase, gelatinase, and collagenase 3 that are implicated in glomerular basement membrane damage.

Objectives To evaluate serum concentration of IL32 in LN patients and its expression in renal biopsy samples.

Methods Serum samples were obtained from 28 LN patients who underwent a renal biopsy as part of the routine clinical assessment, 30 SLE patients without renal involvement (non renal SLE), and 10 healthy controls (HC) matched for sex and age. Sera were collected and stored at -20°C until use. Serum IL32 concentrations were measured using ELISA (R&D system). IL32, expression was also evaluated in renal biopsy samples of patients with active LN (n=20) by using a polyclonal rabbit anti-human IL32. As control, normal perilesional kidney tissue from patients undergoing nephrectomy for kidney malignancies were used. Patients' demographic, clinical and serological data were recorded in an electronically-filled database. All the patients signed a written informed consent and local Ethical Committee approved the protocol. Data were expressed as mean ± standard deviation or median and interquartil range (IQR) when appropriate (non parametric distribution). A p value ≤0.05 was considered significant.

Results The twenty-eight LN patients included in this study were all Caucasian (2 male and 26 women) with a mean age at renal biopsy of 36.8±11.5 years and a mean disease duration of 9.74±11.42 years. Non renal SLE patients (3 male and 27 female) showed a mean age of 46 years ±17 and a mean disease duration of 18±7 years. We found that IL32 serum levels were significantly higher in patients with LN (median 2210, IQR 2404) compared to non renal SLE patients (median 1254, IQR 1334 pg/ml) (p=0.019). No significant difference in IL32 serum levels between LN patients and HC was found. IL32 expression was strongly expressed in renal biopsy samples of LN patients, especially in patients with class III and IV LN, compared to controls (for detail view Figure.1). Analysis of tissue distribution demonstrated IL32 expression in epithelial cells of proximal and distal tubular segments and among mesangial cells. IL-32-expressing cells were also observed among infiltrating inflammatory mononuclear cells scattered in the peri-tubular interstitium.

Conclusions Data from this study showed increased serum and tissue levels of IL32 in LN patients, suggesting a potential role for IL32 in the pathogenesis of LN.

Disclosure of Interest None declared

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