PMID- 21244336
OWN - NLM
STAT- MEDLINE
DCOM- 20111028
LR  - 20110708
IS  - 1607-842X (Electronic)
IS  - 0891-6934 (Linking)
VI  - 44
IP  - 5
DP  - 2011 Aug
TI  - Nephritogenic antibodies bind in glomeruli through interaction with exposed 
      chromatin fragments and not with renal cross-reactive antigens.
PG  - 373-83
LID - 10.3109/08916934.2010.541170 [doi]
AB  - Cross-reactivity of anti-double stranded DNA (anti-dsDNA) antibodies with 
      glomerular antigens has been postulated as a key factor in the development of 
      lupus nephritis. Because no direct proof has been presented on anti-dsDNA 
      antibodies binding in vivo to glomerular structures, we have analysed the binding 
      of potentially nephritogenic anti-dsDNA antibodies to alpha-actinin and laminin. By 
      enzyme-linked immunosorbent assay and surface plasmon resonance (SPR) analyses, 
      we demonstrate that monoclonal antibodies (mAbs) bind both double-stranded DNA 
      and alpha-actinin at high affinity. However, when added to nephritic kidney sections 
      they did not bind to such structures, but rather to nucleosome-containing 
      structures within the mesangial matrix or the glomerular basement membranes 
      (GBMs). Nucleosomes, anti-nuclear antibodies and complexes of them were tested 
      for their binding to glomerular components such as agrin, perlecan and laminin 
      using SPR analysis. Nucleosomes bound to laminin, marginally to agrin, but not to 
      perlecan or heparan sulphate-depleted agrin. Anti-histone H2B and anti-nucleosome 
      antibodies in complex with nucleosomes slightly increased the binding of 
      nucleosomes to agrin, while binding to laminin was slightly decreased compared to 
      nucleosomes alone. In conclusion, the availability of nucleosomal antigens and 
      the binding of these antigens to components of the mesangial matrix and GBM seem 
      crucial for the glomerular deposition of immune complexes.
FAU - Mjelle, Janne Erikke
AU  - Mjelle JE
AD  - Molecular Pathology Research Group, Institute of Medical Biology, University of 
      Tromso, Norway.
FAU - Rekvig, Ole Petter
AU  - Rekvig OP
FAU - Van Der Vlag, Johan
AU  - Van Der Vlag J
FAU - Fenton, Kristin A
AU  - Fenton KA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110119
PL  - England
TA  - Autoimmunity
JT  - Autoimmunity
JID - 8900070
RN  - 0 (Agrin)
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Chromatin)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Nucleosomes)
RN  - 11003-00-2 (Actinin)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Actinin/immunology/metabolism
MH  - Agrin/metabolism
MH  - Animals
MH  - Antibodies, Antinuclear/*immunology/*metabolism
MH  - Antigen-Antibody Complex/immunology/metabolism
MH  - Basement Membrane/immunology/metabolism
MH  - Chromatin/*immunology
MH  - DNA/immunology/metabolism
MH  - Immunoglobulin G/immunology/metabolism
MH  - Kidney Glomerulus/cytology/*metabolism/pathology
MH  - Lupus Nephritis/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred NZB
MH  - Nucleosomes/metabolism
MH  - Protein Binding/immunology
MH  - Surface Plasmon Resonance
EDAT- 2011/01/20 06:00
MHDA- 2011/10/29 06:00
CRDT- 2011/01/20 06:00
PHST- 2011/01/20 06:00 [entrez]
PHST- 2011/01/20 06:00 [pubmed]
PHST- 2011/10/29 06:00 [medline]
AID - 10.3109/08916934.2010.541170 [doi]
PST - ppublish
SO  - Autoimmunity. 2011 Aug;44(5):373-83. doi: 10.3109/08916934.2010.541170. Epub 2011 
      Jan 19.