PMID- 29894515
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20190107
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 6
DP  - 2018
TI  - Tolerogenic beta2-glycoprotein I DNA vaccine and FK506 as an adjuvant attenuates 
      experimental obstetric antiphospholipid syndrome.
PG  - e0198821
LID - 10.1371/journal.pone.0198821 [doi]
LID - e0198821
AB  - DNA vaccines have recently emerged as a therapeutic agent for treating autoimmune 
      diseases, such as multiple sclerosis. Antiphospholipid antibody syndrome (APS) is 
      an autoimmune disease characterized by beta2-glycoprotein I (beta2-GPI)-targeting 
      antiphospholipid antibodies (APAs) and vascular thrombosis or obstetrical 
      complications. To examine the therapeutic potential of a beta2-GPI DNA vaccine, we 
      administered a vaccine mixed with FK506 as an adjuvant to a mouse model of 
      obstetric APS. First, the pCMV3-beta2-GPI DNA vaccine, which encodes the full-length 
      human beta2-GPI gene, was constructed. Then, we administered the beta2-GPI DNA vaccine 
      in 0.1 ml of saline, mixed with or without 100 mug of FK506, intramuscularly to 
      the mice on days 28, 35 and 42. Blood titers of the anti-beta2-GPI antibody, 
      platelet counts, activated partial thromboplastin times (aPTTs), and the 
      percentage of fetal loss were measured. We also stimulated murine splenic T cells 
      ex vivo with beta2-GPI and determined the T helper cell proportion and cytokine 
      secretion. The administration of the beta2-GPI DNA vaccine mixed with FK506 reduced 
      the blood IgG anti-beta2-GPI antibody titers and suppressed APS manifestations in 
      mice. The combination also suppressed interferon-gamma and interleukin (IL)-17A 
      secretion but increased the Treg cell proportion and IL-10 secretion in murine 
      splenic T cells following ex vivo stimulation with beta2-GPI. Our results 
      demonstrated the therapeutic efficacy of a beta2-GPI DNA vaccine and FK506 as an 
      adjuvant in a murine model of obstetric APS. Possible mechanisms include the 
      inhibition of Th1 and Th17 responses and the up-regulation of Treg cells.
FAU - Chao, Ya-Hsuan
AU  - Chao YH
AUID- ORCID: 0000-0001-8283-6589
AD  - Institute of Biomedical Science, National Chung-Hsing University, Taichung, 
      Taiwan.
FAU - Chen, Der-Yuan
AU  - Chen DY
AD  - Division of Immunology and Rheumatology, Department of Internal Medicine, China 
      Medical University Hospital, Taichung, Taiwan.
FAU - Lan, Joung-Liang
AU  - Lan JL
AD  - Division of Immunology and Rheumatology, Department of Internal Medicine, China 
      Medical University Hospital, Taichung, Taiwan.
FAU - Tang, Kuo-Tung
AU  - Tang KT
AD  - Division of Allergy, Immunology and Rheumatology, Taichung Veterans General 
      Hospital, Taichung, Taiwan.
FAU - Lin, Chi-Chien
AU  - Lin CC
AD  - Institute of Biomedical Science, National Chung-Hsing University, Taichung, 
      Taiwan.
AD  - Department of Biotechnology, Asia University, Taichung, Taiwan.
AD  - Department of Medical Research, China Medical University Hospital, Taichung, 
      Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180612
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adjuvants, Pharmaceutic)
RN  - 0 (Antibodies, Antiphospholipid)
RN  - 0 (Autoantibodies)
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Vaccines, DNA)
RN  - 0 (beta 2-Glycoprotein I)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adjuvants, Pharmaceutic/*administration & dosage
MH  - Animals
MH  - Antibodies, Antiphospholipid/blood/immunology
MH  - Antiphospholipid Syndrome/genetics/immunology/pathology/*prevention & control
MH  - Autoantibodies/blood/immunology
MH  - Cell Proliferation
MH  - Cytokines/metabolism
MH  - *Disease Models, Animal
MH  - Female
MH  - Immunosuppressive Agents/administration & dosage
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Pregnancy
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Tacrolimus/*administration & dosage
MH  - Vaccines, DNA/*administration & dosage/genetics
MH  - beta 2-Glycoprotein I/*genetics
PMC - PMC5997307
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/06/13 06:00
MHDA- 2019/01/08 06:00
PMCR- 2018/06/12
CRDT- 2018/06/13 06:00
PHST- 2018/01/15 00:00 [received]
PHST- 2018/05/26 00:00 [accepted]
PHST- 2018/06/13 06:00 [entrez]
PHST- 2018/06/13 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2018/06/12 00:00 [pmc-release]
AID - PONE-D-18-01449 [pii]
AID - 10.1371/journal.pone.0198821 [doi]
PST - epublish
SO  - PLoS One. 2018 Jun 12;13(6):e0198821. doi: 10.1371/journal.pone.0198821. 
      eCollection 2018.