PMID- 22217359
OWN - NLM
STAT- MEDLINE
DCOM- 20121217
LR  - 20211021
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 14
IP  - 1
DP  - 2012 Jan 4
TI  - Tumor necrosis factor alpha release in peripheral blood mononuclear cells of 
      cutaneous lupus and dermatomyositis patients.
PG  - R1
LID - 10.1186/ar3549 [doi]
AB  - INTRODUCTION: Several studies have reported that TNFalpha is substantially increased 
      within skin lesions of patients with discoid lupus erythematosus (DLE), subacute 
      cutaneous lupus erythematosus (SCLE) and dermatomyositis (DM) compared to 
      controls. Elevated TNFalpha has been reported in the sera of some patients with 
      systemic lupus erythematosus, DLE and SCLE, but not in the sera of patients with 
      DM. Because of the key pathogenic role of autoimmunity in these diseases, in this 
      study we sought to evaluate TNFalpha production by a readily available source of 
      immune cells (namely, peripheral blood mononuclear cells (PBMCs)) taken from 
      controls and from patients with cutaneous lupus or DM. METHODS: Freshly isolated 
      PBMCs were cultured overnight, and TNFalpha protein accumulation in conditioned 
      medium was determined. In addition, flow cytometry using cell-type-specific 
      markers was performed to determine the sources of TNFalpha. One-way analysis of 
      variance and Dunnett's multiple comparisons test were performed for statistical 
      comparisons. RESULTS: Accumulation of TNFalpha protein in conditioned medium 
      containing PBMCs from DLE patients, but not from SCLE, TLE or DM patients, was 
      significantly greater (19-fold) than that from controls (P < 0.001). In DLE 
      PBMCs, increased TNFalpha was produced by circulating monocytes and myeloid dendritic 
      cells (mDCs). The mean TNFalpha fluorescence intensity, but not the total number, of 
      both monocytes and mDCs (P < 0.01) from DLE patients was significantly greater 
      (2.3-fold) than that of controls. There were significantly more (13.3-fold) mDCs 
      with intracellular TNFalpha in blood from DLE patients (P < 0.001) and DM patients (P 
      < 0.001) compared to controls. Most importantly, a positive correlation was seen 
      in DLE patients between their disease activity measured using the Cutaneous Lupus 
      Erythematosus Disease Area and Severity Index and TNFalpha protein secretion (r = 
      0.61, P < 0.08). CONCLUSIONS: TNFalpha protein production by PBMCs is greater in DLE 
      patients than in patients with other cutaneous forms of lupus and DM or in 
      controls. Flow cytometric studies demonstrated that circulating monocytes and 
      mDCs contributed to this increased TNFalpha production. Monocytes and mDCs are 
      present in lesional skin, and the increased TNFalpha production by these cells and 
      other PBMCs likely increase the number of inflammatory cells seen in DLE skin 
      relative to other subsets of cutaneous lupus erythematosus and DM. These results 
      provide a possible biological explanation for the denser infiltrate seen in DLE 
      relative to DM.
FAU - Nabatian, Adam S
AU  - Nabatian AS
AD  - Philadelphia Veterans Affairs Medical Center, 38th and Woodland Avenues, 
      Philadelphia, PA 08901, USA.
FAU - Bashir, Muhammad M
AU  - Bashir MM
FAU - Wysocka, Maria
AU  - Wysocka M
FAU - Sharma, Meena
AU  - Sharma M
FAU - Werth, Victoria P
AU  - Werth VP
LA  - eng
GR  - K24-AR 02207/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120104
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Analysis of Variance
MH  - Cells, Cultured
MH  - Dermatomyositis/*blood/pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Lupus Erythematosus, Cutaneous/*blood/pathology
MH  - Lupus Erythematosus, Discoid/blood/pathology
MH  - Male
MH  - Middle Aged
MH  - Tumor Necrosis Factor-alpha/*blood
MH  - Young Adult
PMC - PMC3392787
EDAT- 2012/01/06 06:00
MHDA- 2012/12/18 06:00
PMCR- 2012/01/04
CRDT- 2012/01/06 06:00
PHST- 2010/11/22 00:00 [received]
PHST- 2011/09/21 00:00 [revised]
PHST- 2012/01/04 00:00 [accepted]
PHST- 2012/01/06 06:00 [entrez]
PHST- 2012/01/06 06:00 [pubmed]
PHST- 2012/12/18 06:00 [medline]
PHST- 2012/01/04 00:00 [pmc-release]
AID - ar3549 [pii]
AID - 10.1186/ar3549 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2012 Jan 4;14(1):R1. doi: 10.1186/ar3549.