PMID- 17195231
OWN - NLM
STAT- MEDLINE
DCOM- 20070215
LR  - 20220311
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 56
IP  - 1
DP  - 2007 Jan
TI  - Effects of short-term infliximab therapy on autoantibodies in systemic lupus 
      erythematosus.
PG  - 274-9
AB  - OBJECTIVE: To analyze changes in autoantibodies occurring in patients with 
      systemic lupus erythematosus (SLE) treated with 4 infusions of the chimeric 
      anti-tumor necrosis factor alpha (TNFalpha) antibody infliximab. METHODS: In an 
      open-label safety study, 7 patients with SLE were treated with infliximab at 
      weeks 0, 2, 6, and 10 in combination with azathioprine or methotrexate. 
      Antibodies to double-stranded DNA (dsDNA) were determined by radioimmunoassay and 
      the Crithidia luciliae indirect immunofluorescence assay; anticardiolipin 
      antibodies (aCL) and antibodies to histone and chromatin were measured by 
      enzyme-linked immunosorbent assay. Antihistone antibodies were also analyzed by 
      immunoblotting. Peripheral blood mononuclear cells from healthy individuals and 
      SLE patients were incubated for 2 weeks with or without TNFalpha. TNFalpha was 
      removed by washing and by the addition of infliximab. Apoptotic cells were 
      stained with annexin V and analyzed by flow cytometry. RESULTS: Autoantibodies to 
      dsDNA increased in 5 of 7 patients. Histone, chromatin, and IgM aCL levels were 
      increased in 4 of 7, 6 of 7, and 4 of 7 patients, respectively, peaking 4-10 
      weeks after the last infliximab infusion, but falling to baseline levels or lower 
      thereafter. In the in vitro experiments, TNF withdrawal after long-term 
      incubation with recombinant human TNF led to increased percentages of apoptotic 
      cells. CONCLUSION: While TNF blockade was clinically effective, the majority of 
      SLE patients treated with infliximab showed an increase in autoantibodies to 
      nuclear antigens and phospholipids. These increases were transient and were not 
      associated with disease flares. Increased availability of apoptotic antigens 
      after TNF blockade may play a role in the autoantibody formation induced by TNF 
      blockade.
FAU - Aringer, Martin
AU  - Aringer M
AD  - Medical University of Vienna, Vienna, Austria. martin.aringer@meduniwien.ac.at
FAU - Steiner, Gunter
AU  - Steiner G
FAU - Graninger, Winfried B
AU  - Graninger WB
FAU - Hofler, Elisabeth
AU  - Hofler E
FAU - Steiner, Carl W
AU  - Steiner CW
FAU - Smolen, Josef S
AU  - Smolen JS
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Autoantibodies)
RN  - 0 (Dermatologic Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-49-2 (DNA)
RN  - B72HH48FLU (Infliximab)
RN  - MRK240IY2L (Azathioprine)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Antibodies, Monoclonal/pharmacology/*therapeutic use
MH  - Apoptosis/drug effects
MH  - Autoantibodies/blood
MH  - Azathioprine/therapeutic use
MH  - DNA/immunology
MH  - Dermatologic Agents/pharmacology/*therapeutic use
MH  - Drug Combinations
MH  - Drug Therapy, Combination
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fluorescent Antibody Technique, Indirect
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Infliximab
MH  - Leukocytes, Mononuclear/drug effects/pathology
MH  - Lupus Erythematosus, Systemic/*drug therapy/immunology/pathology
MH  - Methotrexate/therapeutic use
MH  - Radioimmunoassay
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/pharmacology
EDAT- 2006/12/30 09:00
MHDA- 2007/02/16 09:00
CRDT- 2006/12/30 09:00
PHST- 2006/12/30 09:00 [pubmed]
PHST- 2007/02/16 09:00 [medline]
PHST- 2006/12/30 09:00 [entrez]
AID - 10.1002/art.22327 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2007 Jan;56(1):274-9. doi: 10.1002/art.22327.