Welcome to the 2021 LUPUS CORA Meeting Program Scheduling

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Displaying One Session

CORA Topics || ASL06 BIOMARKERS IN AUTOIMMUNE RHEUMATIC CONDITIONS, CORA Topics || ASL21 NOVEL THERAPEUTIC TARGETS IN RHEUMATIC AND AUTOIMMUNE DISEASES, No Topic Needed

Session Type
Parallel Session (CORA)
Date
Thu, 07.10.2021
Session Time
16:45 - 18:45
Room
Hall 4
Chair(s)
  • Carlomaurizio Montecucco (Italy)

Introduction by Chairperson

Presenter
  • Carlomaurizio Montecucco (Italy)
Lecture Time
16:45 - 16:50

Does RA seropositivity counts in disease and therapeutic outcome? YES: seropositive and seronegative patients are different, respond to different therapies, have different clinical manifestations, even genetics

Presenter
  • Josef Smolen (Austria)
Lecture Time
16:50 - 17:05

Does RA seropositivity counts in disease and therapeutic outcome? NO: they are the same

Presenter
  • Roberto Caporali (Italy)
Lecture Time
17:05 - 17:20

Live rebuttal

Presenter
  • Josef Smolen (Austria)
Lecture Time
17:20 - 17:25

Live rebuttal

Presenter
  • Roberto Caporali (Italy)
Lecture Time
17:25 - 17:30

Panel discussion – Live

Lecture Time
17:30 - 18:10

AUTOANTIBODIES TO PROTEIN-ARGININE DEIMINASE (PAD) 1 FROM THE SERA OF RHEUMATOIR ARTHRITIS (RA) PATIENTS RECOGNIZE THEIR ANTIGEN INDEPENDENTLY OF ITS AUTOCITRULLINATION STATUS

Presenter
  • Laura Martinez-Prat (Spain)
Lecture Time
18:10 - 18:16

Abstract

Background and Aims

Protein citrullination, key in Rheumatoid Arthritis (RA), is catalyzed by the protein-arginine deiminase (PAD) enzymes, which require calcium for their activity. These proteins can autocitrullinate but the impact on antibody recognition isn’t fully understood. The objective of this study was to evaluate the effect of PAD1 autocitrullination on the recognition by anti-PAD1 antibodies.

Methods

Full-length PAD1 proteins were recombinantly generated in the absence or presence of calcium. Citrullination status of the produced antigens was evaluated by immunoblotting using the anti-Citrulline (Modified) Detection Kit (MerckMillipore), alongside a commercial PAD1 protein (Cayman). A panel for the detection of anti-PAD1 IgG for the particle-based multi-analyte technology [PMAT, research use only (RUO), Inova Diagnostics] was created by conjugating the citrullinated and non-citrullinated PAD1 versions to magnetic beads. Sera from RA patients (n=14) and healthy controls (n=8) were tested with this panel on the Aptiva instrument (RUO, Inova Diagnostics).

Results

Autocitrullination of PAD1 antigens was confirmed by anti-citrulline immunoblot only for the proteins generated in the presence of calcium (Figure 1). Partial citrullination was observed for the commercial PAD1 antigen. Strong reactivity to both the citrullinated and non-citrullinated PAD1 antigens was observed with the PMAT anti-PAD1 IgG panel, with apparent higher reactivity to the non-citrullinated versions (Figure 2).

figure1.pngfigure2.png

Conclusions

Both citrullinated and non-citrullinated PAD1 were recognized by anti-PAD1 IgG antibodies in the sera of RA patients, supporting the idea that these antibodies recognize unique epitopes in the PAD1 enzyme and are distinct from ACPA.

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Live Q&A

Lecture Time
18:16 - 18:20

PROTEIN-ENGINEERED MOLECULES CARRYING GAD65 EPITOPES AND TARGETING CR1 SELECTIVELY DOWN-MODULATES DISEASE-ASSOCIATED HUMAN B LYMPHOCYTES

Presenter
  • Andrey Tchorbanov (Bulgaria)
Lecture Time
18:20 - 18:26

Abstract

Background and Aims

Autoimmune Diabetes Mellitus (ADM) is an autoimmune metabolic disorder characterized by chronic hyperglycemia, presence of autoreactive T and B cells and autoantibodies against self-antigens. A membrane-bound enzyme on the pancreatic beta-cells, GAD 65, is one of the main autoantigens in type 1 diabetes. Autoantibodies against GAD65 are potentially involved in beta-cells destruction and decline of pancreatic functions.

The human complement receptor type 1 (CR1) on B- and T-lymphocytes has a suppressive activity on these cells. We hypothesized that it may be possible to eliminate GAD65-specific B cells from ADM patients by using chimeric molecules, containing an anti-CR1 antibody, coupled to peptides resembling GAD65 B/T epitopes. These molecules are expected to bind selectively the anti-GAD65 specific B-cells by the co-crosslinking of the immunoglobulin receptor and CR1 and to deliver a suppressive signal.

Methods

Two synthetic peptide epitopes derived from GAD65 protein, and anti-CD35 monoclonal antibody were used for the construction of two chimeras. The immunomodulatory activity of the engineered antibodies was tested in vitro (Epitope prediction, Protein engineering, ELISA, FACS, ELISpot and Proliferation assay) and in vivo (NSG mice transfer) using PBMCs from diabetes patients.

Results

A reduction in the number of anti-GAD65 IgG antibody-secreting plasma cells and increased percentage of apoptotic B lymphocytes was observed after treatment of PBMCs from patients with ADM with engineered antibodies.

Conclusions

The constructed chimeric molecules are able to modulate selectively the activity of GAD65-specific B-lymphocytes and the production of anti-GAD65 IgG auto-antibodies by co-crosslinking of the inhibitory CR1 and the BCR.

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Live Q&A

Lecture Time
18:26 - 18:30

Session summary by Chairperson - Live

Presenter
  • Carlomaurizio Montecucco (Italy)
Lecture Time
18:30 - 18:37