Validation of the IgA1 Detection Method With Gradient Glycosylation by Mass Spectrometry as a Potential Marker of Renal Involvement in Pediatric Rheumatoid Purpura (FOXIGA-2020)

Recherche d'un Marqueur Pronostique de l'Atteinte rénale du Purpura Rhumatoïde de l'Enfant. Validation de la méthode de détection Des IgA1 Avec Gradient de la Glycosylation Par spectrométrie de Masse

In this ancillary study on the FoxTreg cohort, the study investigators will select variables to input and thus develop two models (Linear Discriminant Analysis and Decision Tree). The aim of this study is to validate the method in terms of repeatability, reproducibility, control of pre-analytical conditions and sample conservation, to complete the screening of IgA glycosylation in individuals of the FoxTreg cohort and to refine the glycopeptide signature to predict renal involvement.

Study Overview

• Status: Completed
• Conditions: Pediatric ALL; Rheumatoid Purpura
• Intervention / Treatment: Other: Mass Sepctrometry

• Study Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• France
  • Montpellier, France
    • CHRU de Montpellier
  • Nîmes, France
    • CHU de Nîmes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 16 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is an ancillary study on the patient biobank of the FoxTreg study (NCT02317133). All these patients had given their consent for blood sampling and the conservation of biological samples within the Biological Resources Center (CRB) of Nîmes. A total of 97 patients were recruited, forming three groups:

• Group A (n = 30): patients with active Rheumatoid Purpura according to the criteria of EULAR / PRES / PRINTO 2010 [Ozen et al. 2010].
• Group B (n = 30): patients in remission of Rheumatoid Purpura according to the criteria of EULAR / PRES / PRINTO 2010 [Ozen et al. 2010].
• Group C (n = 37): age-matched control subjects free of infectious / inflammatory / autoimmune pathology.

For this "FoxIgA-2020" study, only sera collected from these patients not analyzed in the "FoxIgA" study will be used.

Thus 52 samples will be analyzed for the FoxIgA-2020 study:

• 10 sera from group A
• 14 sera from group B
• 28 sera of group C

Description

Inclusion Criteria:

Patient sera from biobank of the FoxTreg study (NCT02317133)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute Rheumatoid Purpura	Other: Mass Sepctrometry; Mass spectrometry (LC/MS) of purified immunoglobulins
Rheumatoid Purpura in Remission	Other: Mass Sepctrometry; Mass spectrometry (LC/MS) of purified immunoglobulins
Controls; Without infection, inflammatory or auto-immune pathology	Other: Mass Sepctrometry; Mass spectrometry (LC/MS) of purified immunoglobulins

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycopeptide signature of serum from children with Rheumatoid Purpura	Mass spectrometry to identify the glycopeptides present and their level	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repeatability of mass spectrometry in measuring glycopeptide signature	Mass spectrometry to identify the glycopeptides present and their level	Day 0
Reproducibility of mass spectrometry in measuring glycopeptide signature	Mass spectrometry to identify the glycopeptides present and their level	Day 0
Control of conservation of samples for measuring glycopeptide signature	Mass spectrometry to identify the glycopeptides present and their level	Day 0
Glycopeptide signature of serum from all patients of the cohort	Mass spectrometry to identify the glycopeptides present and their level	Day 0
Difference between a normally glycosylated IgA and an IgA with GalNac polymer in Rheumatoid Purpura patients with / without renal impairment versus controls	Mass spectrometry to identify the glycopeptides present and their level	Day 0
Number of subjects with IgA glycosylation abnormalities in Rheumatoid Purpura patient population with renal impairment polymer in Rheumatoid Purpura patients with / without renal impairment versus controls	Mass spectrometry of IgA	Day 0
Percentage of subjects with IgA glycosylation abnormalities in Rheumatoid Purpura patient population with renal impairment polymer in Rheumatoid Purpura patients with / without renal impairment versus controls	Mass spectrometry of IgA	Day 0
Number of subjects with IgA glycosylation abnormalities in each group	Mass spectrometry of IgA	Day 0
Percentage of subjects with IgA glycosylation abnormalities in each group	Mass spectrometry of IgA	Day 0
Serum immunoglobulin levels in patients with acute Rheumatoid Purpura and in remission	Mass spectrometry of immunoglobulins IgA, IgM and IgG (g/L)	Day 0
Quantification of blood cell lines in patients with acute Rheumatoid Purpura and in remission.	Blood cell lines, particularly Treg and Breg (number/mm3)	Day 0
Serum cytokine levels in patients with acute Rheumatoid Purpura and in remission	pg/ml of TGF-β, IL-1, IL-6, TNF-α, IL-8, IL-10 and IL-17	Day 0
Bacterial Translocation in patients with Rheumatoid Purpura	Plasma levels of 16S rDNA (copies/µl)	Day 0
Plasma levels of LBP in patients with Rheumatoid Purpura	µg/ml	Day 0
Plasma levels of CD14s in patients with Rheumatoid Purpura	µg/ml	Day 0
Bacterial diversity in the gut microbiota in patients with Rheumatoid Purpura	Diversity Index	Day 0

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Tu Anh TRAN, CHU de Nîmes

Publications and helpful links

General Publications

• Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, Al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A, Ruperto N; Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010 May;69(5):798-806. doi: 10.1136/ard.2009.116657.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 22, 2020
• Primary Completion (ACTUAL): December 31, 2021
• Study Completion (ACTUAL): December 31, 2022

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (ACTUAL): December 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Hemostatic Disorders; Vasculitis; Hypersensitivity; Blood Coagulation Disorders; Skin Manifestations; Immune Complex Diseases; Purpura; Purpura, Schoenlein-Henoch
• Other Study ID Numbers: NIMAO/2020-1/TAT-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No