TY - JOUR
T1 - Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients
AU - Draborg, Anette Holck
AU - Sandhu, Noreen
AU - Larsen, Nanna
AU - Lisander Larsen, Janni
AU - Jacobsen, Søren
AU - Houen, Gunnar
PY - 2016
Y1 - 2016
N2 - We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV) antigens in systemic lupus erythematosus (SLE) patients and healthy controls (HCs) to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired EBV-directed T-cell response. The concentrations of 14 cytokines (IL2, IL4, IL5, IL6, IL10, IL12, IL17, IL18, IL1β, IFNγ, TNFα, TNFβ, TGFβ, and GM-CSF) were quantified upon stimulation of whole blood with latent state antigen EBNA1, lytic cycle antigen EBV-EA/D, and the superantigen SEB. To avoid results affected by lack of lymphocytes, we focused on SLE patients with normal levels. Decreased induction of IL12, IFNγ, IL17, and IL6 upon EBNA1 stimulation and that of IFNγ, IL6, TNFβ, IL1β, and GM-CSF upon EBV-EA/D stimulation were detected in SLE patients compared to HCs. IFNγ responses, especially, were shown to be reduced. Induction of several cytokines was furthermore impaired in SLE patients upon SEB stimulation, but no difference was observed in basic levels. Results substantiate the previously proposed impaired regulation of the immune response against latent and lytic cycle EBV infection in SLE patients without lymphopenia. Furthermore, results indicate general dysfunction of leukocytes and their cytokine regulations in SLE patients.
AB - We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV) antigens in systemic lupus erythematosus (SLE) patients and healthy controls (HCs) to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired EBV-directed T-cell response. The concentrations of 14 cytokines (IL2, IL4, IL5, IL6, IL10, IL12, IL17, IL18, IL1β, IFNγ, TNFα, TNFβ, TGFβ, and GM-CSF) were quantified upon stimulation of whole blood with latent state antigen EBNA1, lytic cycle antigen EBV-EA/D, and the superantigen SEB. To avoid results affected by lack of lymphocytes, we focused on SLE patients with normal levels. Decreased induction of IL12, IFNγ, IL17, and IL6 upon EBNA1 stimulation and that of IFNγ, IL6, TNFβ, IL1β, and GM-CSF upon EBV-EA/D stimulation were detected in SLE patients compared to HCs. IFNγ responses, especially, were shown to be reduced. Induction of several cytokines was furthermore impaired in SLE patients upon SEB stimulation, but no difference was observed in basic levels. Results substantiate the previously proposed impaired regulation of the immune response against latent and lytic cycle EBV infection in SLE patients without lymphopenia. Furthermore, results indicate general dysfunction of leukocytes and their cytokine regulations in SLE patients.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antibodies, Viral/blood
KW - Antigens, Viral/pharmacology
KW - Blood Cells/drug effects
KW - Case-Control Studies
KW - Cytokines/genetics
KW - Enterotoxins/pharmacology
KW - Epstein-Barr Virus Infections/complications
KW - Epstein-Barr Virus Nuclear Antigens/pharmacology
KW - Female
KW - Gene Expression Regulation
KW - Herpesvirus 4, Human/immunology
KW - Humans
KW - Lupus Erythematosus, Systemic/complications
KW - Male
KW - Middle Aged
KW - Primary Cell Culture
KW - Recombinant Proteins/pharmacology
KW - Signal Transduction
U2 - 10.1155/2016/6473204
DO - 10.1155/2016/6473204
M3 - Journal article
C2 - 27110576
SN - 2314-8861
VL - 2016
SP - 6473204
JO - Journal of Immunology Research
JF - Journal of Immunology Research
ER -