PARALLEL SESSIONS
Session Type
PARALLEL SESSIONS
Session Time
10:00 - 12:00
Session Icon
Pre Recorded

MECHANISM AND ETIOLOGY OF AUTOIMMUNE DISEASES

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
10:00 - 10:20
Presenter
  • Darja Kanduc, Italy
Session Icon
Pre Recorded

Abstract

Abstract Body

Immunoreactive epitopes derived from HCV, HPV, and SARS-CoV-2 are mostly composed of peptide sequences present in human proteins that — when altered, mutated, deficient or, however, improperly functioning — may associate with a wide range of disorders, from respiratory distress to multiple organ failure. The data indicate cross-reactivity as a basic mechanism linking infections to autoimmune diseases, and further support the concept of peptide uniqueness for designing safe and effective immunotherapies against infectious agents. Scientifically, the data show that a negative selection of self-reactive lymphocytes does not exist, demonstrate the essentially pathogenic nature of the immune response, and reveal the inconsistency of an immune system conceived as capable of discerning and rationally reacting against foreign sequences/structures.

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AUTO-REACTIVITY AGAINST OXIDATIVE POST-TRANSLATIONALLY MODIFIED NEOANTIGENS IN AUTOIMMUNE DISEASES

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
10:20 - 10:35
Presenter
  • Ahuva Nissim, United Kingdom
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Pre Recorded

THE ROLE OF SOLUBLE IL-2R IN THE IL-2/IL-2R PATHWAY: THE PARADOX OF IMMUNITY VERSUS TOLERANCE

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
10:35 - 10:50
Presenter
  • Jan Damoiseaux, Netherlands
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Pre Recorded

IDIOTYPE/ANTI-IDIOTYPE NETWORK AND BIOLOGIC DRUGS-ASSOCIATED IMMUNOGENICITY

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
10:50 - 11:00
Presenter
  • José D. Alves, Portugal
Session Icon
Pre Recorded

MEASUREMENT OF OXIDATIVE STRESS BIOMARKERS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: THE ROLE OF MALONDIALDEHYDE

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
11:00 - 11:10
Presenter
  • CATERINA MARIA GAMBINO, Italy
Session Icon
Pre Recorded

Abstract

Background and Aims

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disease whose pathogenesis still remains unknown. Uncontrolled oxidative stress could play an important role in the disease process, by modifying lipids, DNA and proteins structure and function.

The aim of this study was to determine the levels of selected biomarkers, which are deemed to be promising predictors of oxidative damage, in SLE patients.

Methods

The study included 45 SLE patients and 40 healthy donors (controls), age range 22 – 55 years, who were consecutively admitted at the University Hospital of Palermo.

Oxidative stress was evaluated by measuring the levels of the oxidant and antioxidant biomarkers Malondialdehyde (MDA), sulfhydryl groups, paraxonase 1 and taurine, by using HPLC. The results were expressed as means ± standard deviation. Student's t-distribution was used to compare mean values. A p < 0.05 was considered to be statistically significant.

Results

Oxidative stress, measured by MDA levels, was found significantly increased in SLE patients (5.05 ± 3.36 µmol/L) compared to normal controls (2.79 ± 0.89 µmol/L) (p< 0.0001). No significant changes were observed among other biomarkers.

Conclusions

Preliminary results confirm that SLE patients present increased oxidative stress. MDA is an oxidation product of lipoperoxidation, indicating lipid cell membrane breakdown in SLE.

These findings suggest that MDA may be considered as an oxidative stress biomarker in SLE patients and provide a basis for antioxidant interventions to alleviate clinical manifestations. Further investigations are required to confirm such a hypothesis.

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INHIBITION OF IRF5 HYPER-ACTIVATION PROTECTS FROM LUPUS ONSET AND SEVERITY

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
11:10 - 11:20
Presenter
  • Betsy J. Barnes, United States of America
Session Icon
Pre Recorded

Abstract

Background and Aims

The transcription factor interferon regulatory factor 5 (IRF5) is a central mediator of innate and adaptive immunity. Genetic variations within IRF5 associate with risk of systemic lupus erythematosus (SLE) and mice lacking Irf5 are protected from lupus onset and severity, but how IRF5 functions in the context of SLE disease progression remains unclear.

Methods

Buffy coats were prepared from fresh blood drawn from consented male and female healthy donors and SLE patients. SLE patients fulfilled at least four of the classification criteria for SLE as defined by the ACR. IRF5 activation was determined by imaging flow cytometry on an Amnis Imagestream X Mark II. In vivo studies were performed in NZB/W F1 and MRL/lpr models of murine lupus. IL6 and anti-dsDNA Ig levels were measure by ELISA. Proteinuria was measured by test strip and Bradford protein assay. Serum auto-antibodies were measured by ANA-HEp-2.

Results

In NZB/W F1 mice, we show that murine Irf5 is hyper-activated before clinical onset in a cell type-specific manner. In SLE patients, IRF5 hyper-activation correlated with SLEDAI and dsDNA titers. Treatment of NZB/W F1 and MRL/lpr mice with IRF5 inhibitor attenuated lupus pathology by reducing serum ANA and dsDNA titers, which alleviated kidney pathology and improved overall survival. In ex vivo human studies, inhibitor blocked SLE serum-induced IRF5 activation and reversed basal IRF5 hyper-activation in SLE immune cells.

Conclusions

Altogether, this study provides the first in vivo pre-clinical support for treating SLE patients with an IRF5 inhibitor.

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CIRCULATING EXTRACELLULAR VESICLES HAVE HIGHER EXPRESSION OF COSTIMULATORY MOLECULES IN LUPUS NEPHRITIS

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
11:20 - 11:30
Presenter
  • Marco Quaglia, Italy
Session Icon
Pre Recorded

Abstract

Background and Aims

Extracellular vesicles (EV), microparticles mediating cell-to-cell communication, are involved in immunecomplexes deposition and renal damage in SLE. Aim of this study was to investigate the association between EV plasma levels, their profile of costimulatory molecules expression and presence and severity of Lupus Nephritis (LN).

Methods

Main clinical and laboratory parameters were compared among 67 SLE patients (52 with LN; 15 with rheumatological SLE) and 50 healthy controls (HCs). Plasma levels of EV were evaluated by Nanotrack; EVs were characterised by FACS analysis (20 surface molecules were considered, including ICOS/ICOS-L and PD-1/PD-1L). ICOS and ICOS-L serum levels were also measured (ELISA).

Results

Plasma EV levels and their dimensions were higher in SLE patients with LN as compared to those without LN (p<0.001 for both); no difference was found between pathological classes of LN. However, plasma EV levels correlated with proteinuria (p=0.032) and with SLICC at diagnosis. FACS analysis revealed a peculiar profile of several costimulatory molecules on EVs surface of patients with LN, with a progressively higher expression of ICOS-L, PD-1 and PD-1L moving from HCs to SLE without LN and then to SLE with LN.

Conclusions

Plasma EVs levels and dimensions and their expression of costimulatory molecules, such as ICOS/ICOS-L and PD-1/PD-1L, were higher in EVs from LN patients as compared with rheumatological SLE and HCs. These elements suggest that circulating EV with a peculiar profile of costimulatory molecules expression are involved in mechanisms of renal damage in SLE and may be promising as biomarkers and new therapeutic targets for LN.

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HSP70, A NOVEL REGULATORY MOLECULE IN B CELL MEDIATED SUPPRESSION OF AUTOIMMUNE DISEASES

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
11:30 - 11:40
Presenter
  • Luman Wang, China
Session Icon
Pre Recorded

Abstract

Background and Aims

A recent study demonstrated that regulatory B cells (Bregs) play a crucial role in autoimmune diseases. However, the molecular mechanisms underlying the regulatory function of Bregs remain controversial.

Methods

In this study, we collected human peripheral blood and utilized mouse autoimmune disease models to identify the frequency and function of Bregs in autoimmune diseases such as IBD and Hashimoto thyroiditis.

Results

We found an increased population of Bregs with promoted suppressive function in autoimmune diseases. Moreover, via gene expression microarrays and flow cytometry, we found that HSP70 expression was significantly up-regulated in Bregs especially in diseases. In vitro and in vivo studies explored that inhibiting HSP70 expression changed the regulatory function of Bregs. Furthermore, adoptively transferred Hsp70 overexpressed B cells effectively rescue diseases. Mechanistically, HSP70 modulated Breg suppressive function via directly producing secreted HSP70 and targeting conventional T cells.

Conclusions

Our findings revealed that HSP70 is a novel factor that moderates Breg function, indicating a viable therapy aimed to enhance Breg-mediated production of HSP70.

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THE ROLE OF PAMPS/DAMPS IN THE INDUCTION OF TRAINED INNATE IMMUNITY IN HEALTH AND AUTOIMMUNE DISEASE

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
11:40 - 11:50
Presenter
  • Katerina Laskari, Switzerland
Session Icon
Pre Recorded

Abstract

Background and Aims

The hypothesis that trained immunity contributes to the initiation and perpetuation of the inflammatory response in rheumatoid arthritis (RA) has not been investigated so far. We aim to better investigate pathogen-associated and damage-associated molecular pattern (PAMP and DAMP, respectively)-induced trained immunity in healthy individuals and RA patients.

Methods

Monocytes were isolated from the peripheral blood (PBMCs) of healthy volunteers and active rheumatoid arthritis patients (University Hospital Zurich) by Ficoll-paque centrifugation and negative selection using magnetic beads. The cells were stimulated for 24h with different PAMPs/DAMPs. PBMCs of healthy subjects were re-stimulated 5 days later with the liposaccharide of Escherichia coli (LPS E.coli). The culture supernatant was collected at days 1 and 6.

Results

Citrullinated vimentin, the lipopolysaccharide of Porphyromonasgingivalis (LPS P.gingivalis) and oligomeric S100A4 (oS100A4) induced training in most healthy controls, as suggested by the significantly increased levels of secreted interleukin-6 (IL-6), the chemokine CXCL-1, and CCL20. The citrullinated vimentin had significantly more training capacities compared to the native one. In RA, while the levels of released IL-6 were similar to controls after stimulation with LPS E.coli, we observed a significantly increased immune response after stimulation with LPS P. gingivalis, citrullinated vimentin or oS100A4.

Conclusions

Citrullinated vimentin, LPS of P.gingivalis and oS100Α4 can induce trained immunity in vitro. RA monocytes respond stronger than healthy controls to PAMPs/DAMPS. These observations point towards a possible failed resolution of inflammation in RA due to training capacities of the innate immune cells.

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INTERLEUKIN 1Α IN THE PATHOGENESIS AND TARGETED TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
10:00 - 12:00
Room
HALL C
Lecture Time
11:50 - 12:00
Presenter
  • Giulio Cavalli, Italy
Session Icon
Pre Recorded

Abstract

Background and Aims

The interleukin (IL)-1 family member IL-1α is a ubiquitous and pivotal pro-inflammatory cytokine. The IL‑1a precursor is constitutively present in nearly all cell types in health, but is released upon necrotic cell death as a bioactive mediator. IL‑1a is also expressed by infiltrating myeloid cells within injured tissues. The cytokine binds the IL-1 receptor 1 (IL-1R1), as does IL‑1β, and induces the same pro-inflammatory effects. Being a bioactive precursor released upon tissue damage and necrotic cell death, IL-1α is central to the pathogenesis of numerous conditions characterized by organ or tissue inflammation. This review illustrates the clinical relevance of IL-1α to the pathogenesis of inflammatory diseases, as well as the rationale for the targeted inhibition of this cytokine for treatment of these conditions.

Methods

Comprehensive review of the literature and expert opinion.

Results

IL-1α is involved in the pathogenesis of conditions affecting the lung and respiratory tract, dermatoses and inflammatory skin disorders, systemic sclerosis, myocarditis, pericarditis, myocardial infarction, coronary artery disease, inflammatory thrombosis, as well as complex multifactorial conditions such as COVID-19, vasculitis and Kawasaki disease, Behcet’s syndrome, Sjogren Syndrome, as well as cancer. Three biologics are available to reduce the activities of IL-1α; the monoclonal antibody bermekimab, the IL‑1 soluble receptor rilonacept, and the IL‑1 receptor antagonist anakinra.

Conclusions

Advances in mechanistic understanding and therapeutic management make it incumbent on physicians to be aware of IL-1α and of the opportunity for therapeutic inhibition of this cytokine across in a broad spectrum of diseases.

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