PMID- 34093549
OWN - NLM
STAT- MEDLINE
DCOM- 20211014
LR  - 20211014
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions 
      in Patients With Immune Dysregulation.
PG  - 660506
LID - 10.3389/fimmu.2021.660506 [doi]
LID - 660506
AB  - Intravenous immunoglobulin (IVIG) is an effective immunomodulatory treatment for 
      immune dysregulation diseases. However, the mechanisms by which it reduces 
      systemic inflammation are not well understood. NK cell cytotoxicity is decreased 
      by IVIG in women with reduced fertility, but IVIG effects on NK cells in immune 
      dysregulation are less clear. We hypothesized that IVIG modulation of lymphocyte 
      function, especially in NK cells, is important for resolution of inflammation. 
      Our aim was to identify IVIG-induced changes in a cohort of patients with 
      Kawasaki disease (KD) and those that occur broadly in pediatric patients with 
      various immune dysregulatory diseases. Peripheral blood mononuclear cells (PBMCs) 
      of patients with KD or autoimmune/inflammatory diseases were phenotyped pre and 
      post high dose IVIG treatment by flow cytometry. In KD patients, after IVIG 
      infusion T(reg) cell frequency and the proportion of activated CD25(+) 
      immunoregulatory CD56(bright) NK cells was increased, and multiple lymphocyte 
      subsets showed increased expression of the lymphoid tissue homing receptor CD62L. 
      Importantly, IVIG treatment decreased the frequency of cells expressing the 
      degranulation marker CD107a among cytotoxic CD56(dim) NK cells, which was 
      reflected in a significant reduction in target cell killing and in decreased 
      production of multiple pro-inflammatory mediators. Interestingly, the activating 
      receptor CD336 was expressed on a higher proportion of CD56(bright) NK cells 
      after IVIG in both KD and autoimmune/inflammatory patients while other NK 
      receptors were increased differentially in each cohort. In 
      autoimmune/inflammatory patients IVIG induced the proliferation marker CD71 on a 
      higher percentage of CD56(dim) NK cells, and in contrast to KD patients, 
      CD107a(+) cells were increased in this subset. Furthermore, when PBMCs were 
      stimulated ex vivo with IL-2 or Candida antigen in autologous plasma, more of the 
      CD4(+) T cells of KD patients expressed CD25 after IVIG therapy but fewer 
      cytotoxic T cells were degranulated based on CD107a expression. In summary, IVIG 
      treatment in patients with immune dysregulation has multiple effects, especially 
      on NK cell subsets and CD4(+) T cells, which are compatible with promoting 
      resolution of inflammation. These novel findings provide insight into the 
      immunomodulatory actions of IVIG in autoimmune and inflammatory conditions.
CI  - Copyright (c) 2021 McAlpine, Roberts, Heath, Kasermann, Issekutz, Issekutz and 
      Derfalvi.
FAU - McAlpine, Sarah M
AU  - McAlpine SM
AD  - Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
FAU - Roberts, Sarah E
AU  - Roberts SE
AD  - Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
FAU - Heath, John J
AU  - Heath JJ
AD  - Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
FAU - Kasermann, Fabian
AU  - Kasermann F
AD  - CSL Behring Research, CSL Biologics Research Center, Bern, Switzerland.
FAU - Issekutz, Andrew C
AU  - Issekutz AC
AD  - Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
FAU - Issekutz, Thomas B
AU  - Issekutz TB
AD  - Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
FAU - Derfalvi, Beata
AU  - Derfalvi B
AD  - Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210519
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Immunoglobulins, Intravenous)
SB  - IM
MH  - Adolescent
MH  - CD4-Positive T-Lymphocytes/*drug effects/immunology
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immunoglobulins, Intravenous/*administration & dosage/*therapeutic use
MH  - Immunomodulation
MH  - Inflammation/*therapy
MH  - Killer Cells, Natural/drug effects/*immunology
MH  - Leukocytes, Mononuclear/drug effects/immunology
MH  - Male
MH  - Mucocutaneous Lymph Node Syndrome/drug therapy
MH  - T-Lymphocytes, Regulatory/*drug effects/immunology
PMC - PMC8170153
OTO - NOTNLM
OT  - IVIG
OT  - Kawasaki disease
OT  - NK cell
OT  - autoimmune disease
OT  - immune dysregulation
COIS- Author FK was employed by the company CSL Behring. The authors declare that this 
      study received funding from CSL Behring in the form of an investigator-initiated 
      grant. The funder was not involved in the study design, collection, analysis, 
      interpretation of data or the writing of this article. Author FK read and 
      approved the manuscript.
EDAT- 2021/06/08 06:00
MHDA- 2021/10/15 06:00
PMCR- 2021/01/01
CRDT- 2021/06/07 05:50
PHST- 2021/01/29 00:00 [received]
PHST- 2021/05/04 00:00 [accepted]
PHST- 2021/06/07 05:50 [entrez]
PHST- 2021/06/08 06:00 [pubmed]
PHST- 2021/10/15 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.660506 [doi]
PST - epublish
SO  - Front Immunol. 2021 May 19;12:660506. doi: 10.3389/fimmu.2021.660506. eCollection 
      2021.