Tubulointerstitial nephritis with uveitis: clinico-pathological and immunological study

Abstract

A 10-year-old boy was evaluated for fever, weight loss, uveitis, normocytic, normochromic anemia, renal insufficiency, and hypergammaglobulinemia of 8 weeks' duration. Infectious and neoplastic causes of fever were excluded. A renal biopsy performed in the 4th week of disease revealed diffuse plasmocytic interstitial nephritis. No treatment was prescribed and the patient was transferred to another hospital. Because clinical symptoms and renal insufficiency were still present, in the 8th week of disease a second biopsy was performed, which showed lympho-monocytic interstitial nephritis. At the same time, phenotypic analysis of peripheral blood mononuclear cells was carried out, revealing a significantly decreased number of CD3(+), CD4(+), and CD3(+)/CD8(+) cells, increased non-T CD3(-)/CD8(+) and CD56(+) NK cells, and decreased "naïve" (CD45RA(+)/CD4(+)) and memory (CD45RO(+)/CD8(+)) T lymphocytes. A 6-month course of oral prednisone was prescribed. Clinical symptoms and laboratory findings quickly returned to normal values. After 13 days of corticosteroid therapy, a second phenotypic analysis of peripheral blood mononuclear cells was performed, which revealed normalization of CD3(+), CD4(+), and CD3(+)/CD8(+) cells as well as proportions of non-T CD8(+) and CD56(+) NK lymphocytes, "naïve" and memory cells. This case shows spontaneous evolution of tubulointerstitial infiltrates from plasmacytic to lympho-monocytic, profound disturbances of the immunological system, and the beneficial effect of corticosteroids on both the clinical course and immunological disturbances.

Tubulointerstitial nephritis and uveitis in monozygotic twin boys

“…Acute tubulointerstitial nephritis has been associated with infectious agents [3], toxins, drugs [4], and systemic disease, but there is little known about the pathogenesis associating tubulointerstitial nephritis with eye manifestations. A recent report has provided evidence of transient immune dysregulation during active TINU [5] and suggested an abnormal response to infection.…”

A case of tubulointerstitial nephritis and uveitis syndrome with severe immunologic dysregulation

“…Various immunopathogenetic characteristics have been described. Renal tubulointerstitial infiltrates are primarily composed of activated lymphocytes, plasma cells and activated macrophages [4,5,6,7,8]. Decreased peripheral CD3+, CD4+ and CD8+ lymphocytes, decreased CD4+/CD8+ lymphocyte ratio, increased NK cells [8], lymphokine abnormalities [9] and clinical anergy [1,5] support a disturbance in T cell-mediated immunity.…”

“…Renal tubulointerstitial infiltrates are primarily composed of activated lymphocytes, plasma cells and activated macrophages [4,5,6,7,8]. Decreased peripheral CD3+, CD4+ and CD8+ lymphocytes, decreased CD4+/CD8+ lymphocyte ratio, increased NK cells [8], lymphokine abnormalities [9] and clinical anergy [1,5] support a disturbance in T cell-mediated immunity. Polyclonal hypergammaglobulinemia [3], circulating immune complexes [10] and serologic evidences of autoantibodies such as anti-nuclear antibody (ANA) [9,10], anti-neutrophil cytoplasmic antibody (ANCA) [11,12], anti-cardiolipin antibody (ACA) [13] and anti-tubular basement membrane antibody (ATBMA) [14] support a disturbance in humoral-mediated immunity.…”

Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome, Two New Cases and Review of the Literature

“…TINU syndrome is a disorder characterized by a combination of idiopathic acute tubulointerstitial nephritis and uveitis [4,5], Since it was first documented in 1975 [6,7], only a little more than 200 cases of TINU syndrome have been reported [8,9], with approximately 60% of cases occurring in children [6]. Most of the patients with TINU syndrome are adolescents and young women, with a median age at the onset of 15 (range 9 to 74) years and a 3:1 female-to-male predominance [2,7], but others found an older age group with a male predominance [9].…”

“…Most of the patients with TINU syndrome are adolescents and young women, with a median age at the onset of 15 (range 9 to 74) years and a 3:1 female-to-male predominance [2,7], but others found an older age group with a male predominance [9]. In the other hand, there are arguments suggesting that TINU is underdiagnosed and may be far more common than currently appreciated, especially in young patients in whom mild renal disease does not become symptomatic and/or if diagnostic tests regarding renal involvement are not performed at the time of presentation [8,10].…”