PMID- 7579071
OWN - NLM
STAT- MEDLINE
DCOM- 19951215
LR  - 20210518
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 6
IP  - 1
DP  - 1995 Jul
TI  - Megalin (gp330) possesses an antigenic epitope capable of inducing passive 
      Heymann nephritis independent of the nephritogenic epitope in receptor-associated 
      protein.
PG  - 61-7
AB  - The Heymann nephritis antigenic complex (HNAC) consists of two glycoproteins, 
      megalin (gp330), and the receptor-associated protein (RAP). HNAC is expressed on 
      the surface of the glomerular epithelium where it plays a primary role in the 
      pathogenesis of Heymann nephritis (HN). Several models were previously proposed 
      describing how antibody binding epitopes in HNAC may contribute to the initiation 
      and progression of HN. Although these models suggest that nephritogenic epitopes 
      capable of initiating HN are present in both megalin and RAP, the structural 
      relationship between these epitopes has not been established. Previously a 
      nephritogenic epitope was identified and characterized in RAP that initiates 
      immune complex formation in HN. In this report, the immunologic relationship 
      between nephritogenic epitopes in megalin and RAP were examined to determine 
      whether these epitopes are immunologically distinct or antigenically related. To 
      this end, a polyclonal antibody to megalin was generated that does not recognize 
      RAP by immunoblotting or immunoprecipitation and whether this antibody is capable 
      of inducing passive HN was determined. It was found that antimegalin antibodies 
      devoid of RAP cross-reactivity induced the formation of subepithelial immune 
      deposits (passive HN) when injected into rats. Antibodies eluted from glomeruli 
      of the injected rats recognized only megalin by immunoblotting a cortical extract 
      and did not recognize a RAP fusion protein or any other renal protein. In 
      addition, the eluted antibodies immunoprecipitated two proteolytic fragments of 
      megalin (140 and 75 kd) identifying a pathogenic epitope within a smaller 
      fragment of megalin.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Orlando, R A
AU  - Orlando RA
AD  - Division of Cellular and Molecular Medicine, University of California, San Diego, 
      La Jolla 92093, USA.
FAU - Kerjaschki, D
AU  - Kerjaschki D
FAU - Farquhar, M G
AU  - Farquhar MG
LA  - eng
GR  - DK17724/DK/NIDDK NIH HHS/United States
GR  - F32-DK08885/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Autoantigens)
RN  - 0 (Epitopes)
RN  - 0 (Heymann Nephritis Antigenic Complex)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Animals
MH  - Antibody Specificity
MH  - *Autoantigens
MH  - Cross Reactions
MH  - Disease Models, Animal
MH  - Epitopes
MH  - Glomerulonephritis/*etiology/immunology/pathology
MH  - Heymann Nephritis Antigenic Complex
MH  - Male
MH  - Membrane Glycoproteins/*immunology
MH  - Microscopy, Immunoelectron
MH  - Peptide Fragments/immunology
MH  - Rats
MH  - Rats, Inbred Lew
EDAT- 1995/07/01 00:00
MHDA- 1995/07/01 00:01
CRDT- 1995/07/01 00:00
PHST- 1995/07/01 00:00 [pubmed]
PHST- 1995/07/01 00:01 [medline]
PHST- 1995/07/01 00:00 [entrez]
AID - 10.1681/ASN.V6161 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 1995 Jul;6(1):61-7. doi: 10.1681/ASN.V6161.