Background Regulatory T cells (Tregs) play a key role in the maintenance of immune tolerance and in the development of autoimmune diseases. Expression of Foxp3, a member of forkheadbox family of transcription factors, is specific for Treg cells and can be used for the identification of these cells. Systemic Lupus Erythematosus (SLE) is a prototype autoimmune disease characterized by dysregulated activation of T and B lymphocytes, causing multiple organ damage. There is a high incidence of renal involvement during the course of the disease with varied pathologic and clinical features. Several studies describe a quantitative and/or qualitative abnormalities of peripheral Tregs in SLE. However, the role of Tregs in lupus nephritis (LN) is still unclear.
Objectives Aim of the study:The study aims to investigate the variations of Tregs Foxp3+ in the kidney biopsies inflammatory infiltrate of different LN classes (according to ISN/RPS 2003 criteria) compared to that of ANCA associated crescentic glomerulonephritis (ANCA- CrGN), acute tubulointerstitial nephritis (ATIN) and nephroangiosclerosis (NAS).
Methods Investigation was carried out on renal biopsy samples of 27 patients with histologically proven LN classified according to the ISN/RPS 2003 criteria (class III: 3 patients, class IV: 17 patients, class V: 7 patients), 3 patients with ANCA-CrGN, 6 patients with ATIN, and 2 patients with NAS. Sections of paraffin embedded tissue have been stained by immunohistochemistry with anti-CD3 and anti-FoxP3 antibodies, performed separately on consecutive sections. The number of FoxP3 positive cells and CD3 positive per mm2 was counted after digitalization of slides and application of a dedicated image analysis software.
Results Amount of CD3+ cells was higher in ATIN (5713/mm2) and in ANCA-CrGN (5121/mm2) than in LN-IV (3558/mm2), LN-III (2491/mm2), NAS (2379/mm2) and LN-V (2220/mm2). Instead, we found that the ratio of FoxP3+/CD3+ cells was significantly lower in patients with LN-IV (1,6) and, although less significantly, in patients with CrGN (3) than in course of NAS (3,9), ATN (4), and LN-V (4,5).
Conclusions The data presented herein, demostrate a decrease of Foxp3+ Treg cells in the inflammatory infiltrate of lupus nephritis. These results, although preliminary, suggest an important role of Tregs in the pathogenesis of autoimmune diseases, particularly during the most active phases of LN, as observed in LN-IV class.
Disclosure of Interest None Declared