PMID- 10540174
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20220317
IS  - 0009-9104 (Print)
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Linking)
VI  - 118
IP  - 1
DP  - 1999 Oct
TI  - Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity 
      to ultraviolet radiation and to antibody-mediated cytotoxicity.
PG  - 164-70
AB  - Keratinocyte cytotoxicity is an important component of the immunopathology of 
      photosensitive lupus erythematosus, and antibody-dependent cell-mediated 
      cytotoxicity (ADCC) has been shown to be an important mechanism by which 
      autoantibodies, especially those specific for SS-A/Ro, can induce keratinocyte 
      damage in models of photosensitive lupus. We provide further evidence that 
      keratinocytes from patients with photosensitive lupus show significantly greater 
      ultraviolet radiation (UVR)-induced cytotoxicity, and that ADCC of these targets 
      is especially enhanced by autologous patient's serum or by anti-SS-A/Ro+ sera. 
      Keratinocytes from normal uninvolved skin of 29 patients with cutaneous lupus 
      erythematosus (LE) were grown in cell culture and tested as targets in 
      cytotoxicity experiments in vitro. Cultured keratinocytes from patients with 
      systemic lupus erythematosus (SLE) and subacute cutaneous lupus erythematosus 
      (SCLE) showed significantly greater cytotoxicity following UVR treatment than did 
      keratinocytes from normal adult controls or from neonatal foreskins (P < 0.01). 
      The same cultures also showed greater UVR-induced binding of IgG from 
      fractionated anti-SS-A/Ro+ preparations. ADCC experiments were also performed 
      using keratinocytes cultured from patients with SLE, SCLE, discoid lupus 
      erythematosus (DLE), and normal controls. When keratinocytes were incubated in 
      autologous serum plus a standard mononuclear cell effector population, the 
      percentage of ADCC observed was significantly greater in cultures containing 
      keratinocytes and sera from the SLE and SCLE patients (P < 0.001). When cultured 
      keratinocytes were added to different IgG antibody probes, plus standard 
      mononuclear effector populations, greater ADCC was seen using the anti-SS-A/Ro 
      probe and keratinocytes from patients with SLE or SCLE. With normal human 
      neonatal keratinocyte targets, the anti-SS-A/Ro probe induced greater ADCC than 
      that seen with anti-ssDNA or normal human serum. We have shown that keratinocytes 
      from patients with some forms of lupus erythematosus (SLE and SCLE) show greater 
      cytotoxicity in vitro when irradiated with UVR, and greater susceptibility to 
      ADCC whether the antibody source is their own serum or an anti-SS-A/Ro probe.
FAU - Furukawa, F
AU  - Furukawa F
AD  - Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, 
      Japan. ofuku@wakayama-med.ac.jp
FAU - Itoh, T
AU  - Itoh T
FAU - Wakita, H
AU  - Wakita H
FAU - Yagi, H
AU  - Yagi H
FAU - Tokura, Y
AU  - Tokura Y
FAU - Norris, D A
AU  - Norris DA
FAU - Takigawa, M
AU  - Takigawa M
LA  - eng
GR  - R01 AR026427/AR/NIAMS NIH HHS/United States
GR  - R01-AR26427-18/AR/NIAMS 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  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (SS-A antibodies)
SB  - IM
MH  - Adult
MH  - Antibodies, Antinuclear/isolation & purification/metabolism
MH  - Antibody-Dependent Cell Cytotoxicity/immunology/*radiation effects
MH  - Cell Membrane/metabolism
MH  - Cells, Cultured
MH  - Cytotoxicity Tests, Immunologic
MH  - Female
MH  - Humans
MH  - Keratinocytes/cytology/*immunology/metabolism/*radiation effects
MH  - Lupus Erythematosus, Systemic/immunology/*pathology
MH  - Male
MH  - Middle Aged
MH  - *Ultraviolet Rays
PMC - PMC1905409
EDAT- 1999/10/30 00:00
MHDA- 1999/10/30 00:01
PMCR- 2000/10/01
CRDT- 1999/10/30 00:00
PHST- 1999/10/30 00:00 [pubmed]
PHST- 1999/10/30 00:01 [medline]
PHST- 1999/10/30 00:00 [entrez]
PHST- 2000/10/01 00:00 [pmc-release]
AID - cei1026 [pii]
AID - 10.1046/j.1365-2249.1999.01026.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 1999 Oct;118(1):164-70. doi: 10.1046/j.1365-2249.1999.01026.x.