Impact of Gender and Pubertal Status on Human Plasmacytoid Dendritic Cells. PLASMACYTOKID

Not Applicable

Terminated

• Conditions: Innate Immune Responses
• Interventions: Biological: Blood Plasmacytoid dendritic cells (pDCs) absolute number

• Registration Number: NCT02956980
• Lead Sponsor: University Hospital, Toulouse

Brief Summary

Differences in pDCs function related to gender have been demonstrated in adults but have never been addressed in children. Yet, differences in immune responses related to gender also exist in children, both in responses to pathogens and susceptibility to autoimmune diseases. The investigators suppose that these differences are partly linked to difference in pDCs functions. This study aim is to compare pDCs functions in children based on gender and pubertal status. This study will be performed in healthy children, boys with Klinefelter syndrome and girls with Turner syndrome.

Detailed Description

There are differences in immune responses according to gender. Women have stronger responses against pathogens, especially viruses but are also more susceptible to develop autoimmune diseases. These points reflect more robust innate and adaptive responses in women. Plasmacytoid dendritic cells (pDCs) are key actor of innate immune responses through their ability to produce large amounts of type 1 Interferons (IFN1) secondary to stimulation of their toll like receptors (TLR) 7 and 9 by nucleic acids. Thus, pDCs play a major beneficial role in antiviral responses. In autoimmune diseases like Systemic Erythematous Lupus, pDCs also play a role, mostly deleterious, through inappropriate production of IFN1 upon stimulation of their TLR's by self nucleic acids. In these diseases, pDCs from women have been demonstrated to produce more IFN1 as compared to men, a phenomenon that can be linked to both hormonal and genetic factors. Indeed, the investigators research team demonstrated that IFN1 production by human pDCs can be increased by oestradiol through a specific receptor present in pDCs. Regarding genetics, some studies recently shown in a humanized mouse model, that pDCs developing from female hematopoietic precursor cells have an enhanced TLR 7 mediated IFN1 response as compared to male ones. These results indicate that X chromosome dosage could contribute independently to the enhanced TLR 7 mediated response of pDCs from women. Although some genes implicated in IFN1 production are on the X chromosome, including TLR 7, the mechanism underlying this observation are presently unknown.

Study Timeline

• Study First Submitted: 2016-11-03
• Study First Submitted QC: 2016-11-04
• Study First Posted: 2016-11-06
• Study Start: 2017-06-21
• Primary Completion: 2018-12-31
• Study Completion: 2018-12-31
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-11
• Last Update Posted: 2019-07-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

1. Pediatric patients (0-18 years old):

   • Group 1 : Age<8 years old
   • Group 2 : Age>12 years old

2. Body weight >10kgs

3. Pubescent (group 2) or non-pubescent (group 1)

4. Written consent of parents

Exclusion Criteria

1. Active infectious disease
2. Known perturbations of immune and/or inflammatory systems
3. Oral or subcutaneous contraception in pubescent girls

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: non-pubescent children	Blood Plasmacytoid dendritic cells (pDCs) absolute number	70 non-pubescent children (25 healthy boys, 25 healthy girls, 10 boys with Klinefelter syndrome and 10 girls with Turner syndrome) Two 7 ml tubes of blood will be taken to perform the functional assays as well as the quantification of Blood Plasmacytoid dendritic cells (pDCs) absolute number in this 70 non-pubescent children.
Group 2: pubescent healthy children	Blood Plasmacytoid dendritic cells (pDCs) absolute number	50 pubescent healthy children (25 boys and 25 girls) Two 7 ml tubes of blood will be taken to perform the functional assays as well as the quantification of Blood Plasmacytoid dendritic cells (pDCs) absolute number in this 50 pubescent healthy children.

Primary Outcome Measures

Name	Time	Method
percentage of IFN1 producing pDCs	1 day	Assessment of the percentage of IFN1 producing pDCs after ex vivo stimulation with TLR 7, 9 and 8 ligands.

Secondary Outcome Measures

Name	Time	Method
percentage of pDc, cDC and monocytes in circulating blood	1 day	Innate immune functions of pDCs, cDC and Monocytes present in the circulating blood of boys with Klinefelter syndrome or girls with Turner syndrome will be evaluated identically to healthy children.
percentage of cells producing TNF alpha and Interleukin(IL)-12p40	1 day	Innate immune functions of conventional dendritic cells (cDC) and monocytes present in the circulating blood of healthy children will be assessed by the percentage of cells producing TNF alpha and IL-12p40.
Percentage of IFN1 producing tumor necrosis factor(TNF)-alpha	1 day	Innate immune functions of pDCs present in the circulating blood of healthy children will be assessed by the percentage of pDCs producing TNF-alpha.
IFN1 concentration in the peripheral blood mononuclear cells circulating (PBMC) culture supernatant.	1 day	The innate immune functions of pDCs present in the circulating blood of healthy children will also be assessed by measuring the concentration IFN1 present in the culture supernatant of PBMC stimulated with TLR 7 or TLR 9 ligands.
Number of DC (cDC and pDC) by milliliter of blood	1 day	The number of DCs (pDCs CDC) / ml of blood flowing will be quantified and expressed in blood and percentage of PBMCs.

Trial Locations

Locations (1)

CHU Toulouse, Hôpital des Enfants; 🇫🇷 Toulouse, France