PMID- 16868973
OWN - NLM
STAT- MEDLINE
DCOM- 20060919
LR  - 20071114
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 54
IP  - 8
DP  - 2006 Aug
TI  - Association of alpha-actinin-binding anti-double-stranded DNA antibodies with 
      lupus nephritis.
PG  - 2523-32
AB  - OBJECTIVE: Anti-double-stranded DNA (anti-dsDNA) antibodies may contribute to the 
      pathogenesis of glomerulonephritis (GN) by cross-reacting with alpha-actinin in 
      murine models and in some patients with systemic lupus erythematosus (SLE). We 
      therefore sought to determine possible disease associations with serologic and 
      clinical features and to characterize this new autoantibody specificity. METHODS: 
      One hundred patients with SLE were recruited into this multicenter study, as well 
      as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical 
      disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the 
      anti-DNA component). Anti-dsDNA antibodies were detected by conventional 
      enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay 
      (EIA). Anti-alpha-actinin antibodies were detected by ELISA, and their 
      specificity was confirmed by Western blotting and by indirect immunofluorescence 
      using rat kidney sections and mesangial cells as substrates. Highly positive sera 
      were selected for absorption experiments and were affinity-purified for 
      cross-reactivity studies and measurement of antibody avidity. RESULTS: Sera from 
      62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had 
      anti-alpha-actinin antibodies, as compared with 1 of the 38 sera without 
      anti-dsDNA antibodies. Of the 22 patients with anti-alpha-actinin antibodies, 10 
      had GN, as compared with 14 of the 78 without anti-alpha-actinin antibodies (P < 
      0.01). In patients with GN, anti-alpha-actinin, but not anti-dsDNA, antibodies 
      correlated with the SLEDAI score (minus the anti-DNA component) and with 
      treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with 
      alpha-actinin exhibited high avidity for dsDNA, as determined using a commercial 
      EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA. 
      CONCLUSION: The alpha-actinin-binding antibodies are significantly associated 
      with GN in SLE. Whether such autoantibodies may anticipate the development of 
      this complication of SLE remains to be verified.
FAU - Renaudineau, Yves
AU  - Renaudineau Y
AD  - Brest University Medical School, Brest, France.
FAU - Croquefer, Sabine
AU  - Croquefer S
FAU - Jousse, Sandrine
AU  - Jousse S
FAU - Renaudineau, Eric
AU  - Renaudineau E
FAU - Devauchelle, Valerie
AU  - Devauchelle V
FAU - Gueguen, Paul
AU  - Gueguen P
FAU - Hanrotel, Catherine
AU  - Hanrotel C
FAU - Gilburd, Boris
AU  - Gilburd B
FAU - Saraux, Alain
AU  - Saraux A
FAU - Shoenfeld, Yehuda
AU  - Shoenfeld Y
FAU - Putterman, Chaim
AU  - Putterman C
FAU - Youinou, Pierre
AU  - Youinou P
LA  - eng
GR  - P01-AI-51392/AI/NIAID NIH HHS/United States
GR  - R01-AR-48692/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Actins)
RN  - 0 (Antibodies, Antinuclear)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Actins/*immunology
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies, Antinuclear/*blood
MH  - Blotting, Western
MH  - DNA/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Fluorescent Antibody Technique, Indirect
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Lupus Nephritis/*immunology/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Severity of Illness Index
EDAT- 2006/07/27 09:00
MHDA- 2006/09/20 09:00
CRDT- 2006/07/27 09:00
PHST- 2006/07/27 09:00 [pubmed]
PHST- 2006/09/20 09:00 [medline]
PHST- 2006/07/27 09:00 [entrez]
AID - 10.1002/art.22015 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2006 Aug;54(8):2523-32. doi: 10.1002/art.22015.