Clinical trial NCT02956980: Impact of Gender and Pubertal Status on Human Plasmacytoid Dendritic Cells. PLASMACYTOKID
Official title: Impact of Gender and Pubertal Status on Human Plasmacytoid Dendritic Cells - PLASMACYTOKID Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Innate Immune Responses
Keywords: type 1 interferons
children
gender
pubertal status
sex difference
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2016-11-06
Enrollment: 78
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

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.

Eligibility criteria: 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

Primary outcomes:
measure: percentage of IFN1 producing pDCs
timeFrame: 1 day
Secondary outcomes:
measure: Percentage of IFN1 producing tumor necrosis factor(TNF)-alpha
timeFrame: 1 day
measure: IFN1 concentration in the peripheral blood mononuclear cells circulating (PBMC) culture supernatant.
timeFrame: 1 day
measure: percentage of cells producing TNF alpha and Interleukin(IL)-12p40
timeFrame: 1 day
measure: percentage of pDc, cDC and monocytes in circulating blood
timeFrame: 1 day
measure: Number of DC (cDC and pDC) by milliliter of blood
timeFrame: 1 day
Other outcomes:
Locations:
city: Toulouse
country: France
facility: CHU Toulouse, Hôpital des Enfants
Study officials:
affiliation: CHU Toulouse, Hôpital des Enfants
name: Arnaud Garnier, MD
role: PRINCIPAL_INVESTIGATOR
References: