HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hyman, L. R. Articles by Steinberg, A. D. Search for Related Content PubMed Articles by Hyman, L. R. Articles by Steinberg, A. D.

Immunopathogenesis of Autoimmune Tubulointerstitial Nephritis

I. Demonstration of Differential Susceptibility in Strain II and Strain XIII Guinea Pigs¹

From the Arthritis and Rheumatism Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014, the Pediatric Renal Section, Department of Pediatrics, Walter Reed Army Medical Center, Washington, District of Columbia 20012, and the Department of Experimental Pathology, Walter Reed Army Institute of Research, Washington, District of Columbia 20012

Abstract

Autoimmune tubulointerstitial nephritis (TN) was induced in strain XIII and Hartley but not strain II guinea pigs after immunization with rabbit tubular basement membranes (TBM) in CFA. Strain XIII guinea pigs developed extensive autoimmune TN associated with high anti-TBM (aTBM) antibody titers and linear deposits of IgG along renal cortical TBM after immunization with 10 µg to 10 mg of TBM. In addition, autoimmune TN was passively transferred to strain XIII animals by the i.p. injection of aTBM sera obtained from actively immunized Hartley guinea pigs. In contrast, strain II guinea pigs did not develop autoimmune TN after active immunization (10 µg to 10 mg) with rabbit TBM in CFA, and only produced high aTBM antibody titers with the highest immunizing antigen dose. At this dose (10 mg) the strain II animals demonstrated linear deposits of IgG along renal cortical TBM but did not develop autoimmune TN. Further, recipient strain II guinea pigs did not develop autoimmune TN after passive transfer of aTBM antisera despite renal cortical tubular deposition of aTBM antibodies. Both inbred guinea pig strains produced antibodies reactive with rabbit and rat renal basement membranes. No evidence for differences in nephritogenic TBM antigens could be demonstrated between strain XIII and strain II TBM. These observations indicate that 1) genetic factor(s) influence the production of antibodies reactive to autologous TBM, 2) after the deposition of antibodies on the TBM, additional or related genetic factor(s) determine the full expression of this autoimmune renal disease, and 3) aTBM antibody deposition on renal TBM is not sufficient to elicit autoimmune TN.

Footnotes

¹ This work was presented in part at the 59th Annual meeting of the Federation of American Societies for Experimental Biology, April 13 to 18, 1975, Atlantic City, New Jersey.

² Address reprint requests to Lawrence R. Hyman, M.D., Department of Pediatrics, Walter Reed Army Medical Center, Washington, District of Columbia 20012.