Sari H Rytkönen1, Petri Kulmala2,3, Helena Autio-Harmainen4, Pekka Arikoski5, Kira Endén6,7, Janne Kataja8, Tuomo Karttunen4, Matti Nuutinen2, Timo Jahnukainen7. 1. PEDEGO Research Unit and Medical Research Center (MRC) Oulu, University of Oulu and Oulu University Hospital, Box 23, 90029 OYS, Oulu, Finland. sari.rytkonen@fimnet.fi. 2. PEDEGO Research Unit and Medical Research Center (MRC) Oulu, University of Oulu and Oulu University Hospital, Box 23, 90029 OYS, Oulu, Finland. 3. Biomedicine Research Unit, Clinical Microbiology and Immunology, University of Oulu, Oulu, Finland. 4. Cancer and Translational Medicine Research Unit, University of Oulu, and Department of Pathology, Oulu University Hospital, Box 50, 90029 OYS, Oulu, Finland. 5. Department of Pediatrics, University of Eastern-Finland and Kuopio University Hospital, Box 100, 70029 KYS, Kuopio, Finland. 6. Department of Pediatrics, Tampere University Hospital, Box 2000, 33521 TAYS, Tampere, Finland. 7. Department of Pediatric Nephrology and Transplantation, Children's Hospital, Helsinki University Hospital and Helsinki University, Stenbäckinkatu 11, Box 281, 00029, Helsinki, Finland. 8. Pediatric and Adolescent Medicine, Turku University Hospital, Box 51, 20520 TYKS, Turku, Finland.
Abstract
BACKGROUND: Tubulointerstitial nephritis (TIN) is an inflammatory disease of unknown pathogenesis. To evaluate a possible role of regulatory T cells (Tregs) in the pathophysiology of TIN with (TINU) and without uveitis, we investigated the presence and quantity of FOXP3+ T regulatory lymphocytes in diagnostic kidney biopsies from pediatric patients. METHODS: A total of 33 patients (14 TIN and 19 TINU) were enrolled. The quantity of CD4+, FOXP3+ and double-positive T cells in formalin-fixed kidney biopsies was determined using double label immunohistochemistry with anti-human CD4 and FOXP3 antibodies. RESULTS: FOXP3 staining was successful in all 33 patients. In patients with chronic uveitis, the density of FOXP3+ cells was significantly lower (p = 0.046) than in TIN patients without uveitis or with uveitis lasting <3 months. CD4+ staining was successful in 23 patients. The density of all lymphocytes (CD4+, CD4+FOXP3+ and FOXP3+ cells) was significantly lower (p = 0.023) in patients with chronic uveitis than in other patients. CONCLUSIONS: FOXP3+ T cells are present in kidney biopsy samples from TIN and TINU patients. In patients with chronic uveitis, the density of FOXP3+ T cells is significantly lower than in other patients, suggesting a different pathomechanism for these clinical conditions.
BACKGROUND:Tubulointerstitial nephritis (TIN) is an inflammatory disease of unknown pathogenesis. To evaluate a possible role of regulatory T cells (Tregs) in the pathophysiology of TIN with (TINU) and without uveitis, we investigated the presence and quantity of FOXP3+ T regulatory lymphocytes in diagnostic kidney biopsies from pediatric patients. METHODS: A total of 33 patients (14 TIN and 19 TINU) were enrolled. The quantity of CD4+, FOXP3+ and double-positive T cells in formalin-fixed kidney biopsies was determined using double label immunohistochemistry with anti-humanCD4 and FOXP3 antibodies. RESULTS:FOXP3 staining was successful in all 33 patients. In patients with chronic uveitis, the density of FOXP3+ cells was significantly lower (p = 0.046) than in TIN patients without uveitis or with uveitis lasting <3 months. CD4+ staining was successful in 23 patients. The density of all lymphocytes (CD4+, CD4+FOXP3+ and FOXP3+ cells) was significantly lower (p = 0.023) in patients with chronic uveitis than in other patients. CONCLUSIONS:FOXP3+ T cells are present in kidney biopsy samples from TIN and TINU patients. In patients with chronic uveitis, the density of FOXP3+ T cells is significantly lower than in other patients, suggesting a different pathomechanism for these clinical conditions.
Entities:
Keywords:
Biopsy; Child; FOXP3; Regulatory T cell; Tubulointerstitial nephritis; Uveitis
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