Involvement of drug-specific T cells in acute drug-induced interstitial nephritis

Spanou, Zoi; Keller, Monika; Britschgi, Markus; Yawalkar, Nikhil; Fehr, Thomas; Neuweiler, Jörg; Gugger, Mathias; Mohaupt, Markus; Pichler, Werner J (2006). Involvement of drug-specific T cells in acute drug-induced interstitial nephritis. Journal of the American Society of Nephrology, 17(10), pp. 2919-27. Hagerstown, Md.: Lippincott Williams & Wilkins 10.1681/ASN.2006050418

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Drug-induced interstitial nephritis can be caused by a plethora of drugs and is characterized by a sudden impairment of renal function, mild proteinuria, and sterile pyuria. For investigation of the possible pathomechanism of this disease, drug-specific T cells were analyzed, their function was characterized, and these in vitro findings were correlated to histopathologic changes that were observed in kidney biopsy specimens. Peripheral blood mononuclear cells from three patients showed a proliferative response to only one of the administered drugs, namely flucloxacillin, penicillin G, and disulfiram, respectively. The in vitro analysis of the flucloxacillin-reactive cells showed an oligoclonal immune response with an outgrowth of T cells bearing the T cell receptor Vbeta9 and Vbeta21.3. Moreover, flucloxacillin-specific T cell clones could be generated from peripheral blood, they expressed CD4 and the alphabeta-T cell receptor, and showed a heterogeneous cytokine secretion pattern with no clear commitment to either a Th1- or Th2-type response. The immunohistochemistry of kidney biopsies of these patients revealed cell infiltrations that consisted mostly of T cells (CD4+ and/or CD8+). An augmented presence of IL-5, eosinophils, neutrophils, CD68+ cells, and IL-12 was observed. In agreement with negative cytotoxicity assays, no cytotoxicity-related molecules such as Fas and perforin were detected by immunohistochemistry. The data indicate that drug-specific T cells are activated locally and orchestrate a local inflammation via secretion of various cytokines, the type of which depends on the cytokine pattern secreted and which probably is responsible for the renal damage.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Spanou, Zoi; Yawalkar, Nikhil; Gugger, Mathias; Mohaupt, Markus and Pichler, Werner Joseph

ISSN:

1046-6673

ISBN:

16943303

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Markus Georg Mohaupt

Date Deposited:

04 Oct 2013 14:45

Last Modified:

26 Feb 2014 04:37

Publisher DOI:

10.1681/ASN.2006050418

PubMed ID:

16943303

Web of Science ID:

000240926500032

URI:

https://boris.unibe.ch/id/eprint/18509 (FactScience: 680)

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