Welcome to the Autoimmunity 2021 Congress Calendar

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PARALLEL SESSIONS
Session Type
PARALLEL SESSIONS
Session Time
15:30 - 17:30
Session Icon
Pre Recorded

WHAT IS NEW IN THE THERAPY OF SYSTEMIC VASCULITIDES IN 2020?

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
15:30 - 17:30
Room
HALL F
Lecture Time
15:30 - 15:50
Session Icon
Pre Recorded

TREATMENT OF LARGE VESSEL VASCULITIS

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
15:30 - 17:30
Room
HALL F
Lecture Time
15:50 - 16:10
Session Icon
Pre Recorded

PROTECTIVE EFFECTS OF EXTRACELLULAR VESICLES DERIVED FROM ENDOTHELIAL PROGENITOR CELLS IN ANCA-ASSOCIATED VASCULITIS

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
15:30 - 17:30
Room
HALL F
Lecture Time
16:10 - 16:20
Session Icon
Pre Recorded

Abstract

Background and Aims

Complement cascade plays a key role in neutrophil activation and endothelial injury in ANCA-associated vasculitis (AAV). Endothelial Progenitor Cells (EPC) induce tissue regeneration through the release of paracrine factors including extracellular vesicles (EV), microparticles involved in cell-to-cell communication through transfer of proteins, mRNAs and microRNAs. Aim of the study was to evaluate the protective role of EPC EV in AAV-associated neutrophil/endothelial alterations.

Methods

Ten AAV patients were enrolled in the study. Circulating EPC (CD34+/flk-1+) were evaluated by FACS. EV were isolated by ultracentrifugation and characterized for size and protein/RNA content. We established an in vitro model to evaluate the effects of EPC-EV on neutrophil activation and endothelial injury.

Results

Patients’ characteristics: age: 59.5±24; male 6/10; c-ANCA: 5/10 ; creatinine: 3.8±1.68 mg/dl. In primed neutrophils, plasma from ANCA+ patients up-regulated C5b9 and increased C5a/ROS production. EPC-EV reduced these detrimental effects through the transfer of specific mRNA coding for complement inhibitors (CD55, CD59, Factor H). EPC-EV decreased the adhesion of activated neutrophils to endothelial cells. Moreover, when quiescent endothelial cells were incubated with neutrophil supernatants, we observed an increased expression of E-selectin, ICAM-1, angiopoietin-2 and ROS, triggering of apoptosis and inhibition of angiogenesis. EPC-EV reduced all these detrimental effects through endothelial transfer of specific mRNA and microRNA (miR-126 and miR-296) able to modulate inflammation, apoptosis and angiogenesis.

Conclusions

EPC-derived EV may represent an innovative therapeutic approach for AAV for their beneficial effects on complement-mediated neutrophil activation and endothelial injury. This is mainly due to the transfer of specific RNAs from EV to target cells.

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GIANT CELLS ARTERITIS: TOCILIZUMAB DISCONTINUATION AFTER 52 WEEKS OF TREATMENT IS A FEASIBLE OPTION? A RETROSPECTIVE MONOCENTRIC STUDY ON LONG-TERM TREATMENT IN 32 PATIENTS

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
15:30 - 17:30
Room
HALL F
Lecture Time
16:20 - 16:30
Session Icon
Pre Recorded

Abstract

Background and Aims

The efficacy of Tocilizumab (TCZ) in Giant Cells Arteritis (GCA) is supported by two randomized controlled studies (1,2) in which TCZ allowed to achieved remission after 52 weeks of treatment but after treatment discontinuation half of patients relapsed. The aim of this study is to analyze the efficacy and safety of long-term treatment with Tocilizumab in a monocentric cohort of GCA patients.

Methods

We collected retrospectively clinical data from 32 GCA patients treated with TCZ.

Results

32 GCA patients were treated with Tocilizumab (M/F=25/7; years=74(59-81)). Most of them achieved and maintained clinical remission (T1: 69%, T3: 91%, T6: 96%, T12: 100%), with serological and FDG-PET/CT scan improvement. 19 patients were treated for more than 52 weeks and in 13 of them a dose tapering was performed, while in 2 cases TCZ was suspended for disease remission. Only two patients relapsed: one during TCZ tapering, one after TCZ discontinuation. During the follow up ten cases of mild infections and a case of urinary sepsis were reported; in patients treated for more than 1 year there wasn’t an increased incidence of side effects.

Conclusions

In our cohort of patients, the efficacy of Tocilizumab in the induction and maintenance of remission of GCA was confirmed. TCZ demonstrated also an important steroid sparing effect and an acceptable safety profile. Moreover, long-term treatment with TCZ seems to prevent relapse of the disease, suggesting that Tocilizumab treatment should be continue for more than 52 weeks with efficacy and safety.

(1) Villiger PM, Lancet 2016. (2) Stone JH, NEJM, 2017.

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ALLERGIC PROFILE AND ALLERGEN-SPECIFIC IMMUNOTHERAPY IN EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA): A SINGLE CENTER OBSERVATIONAL STUDY.

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
15:30 - 17:30
Room
HALL F
Lecture Time
16:30 - 16:40
Presenter
Session Icon
Pre Recorded

Abstract

Background and Aims

Eosinophilic granulomatosis with polyangiitis (EGPA), is a systemic disease characterized by late onset asthma, eosinophilia and vasculitis. About 20-30% of patients with EGPA displays inhalant allergies, while prevalence of food and drug allergy is unknown. Some authors hypothesized a role of allergen-specific immunotherapy (ASIT) as trigger of disease. Aim of the study is to establish the prevalence of allergies among EGPA patients and to determine whether atopy or ASIT could influence clinical expression of the disease.

Methods

Retrospective demographic and clinical data collection of EGPA patients in our center.

Results

Fifty-three (53) patients with definitive diagnosis of EGPA have been included in the analysis among which 25 (47.2%) with allergy history. Among allergic patients 15 (60%) resulted sensitized towards inhalants and among them 13 (86.7%) displayed multiple sensitization. Drug allergy affected 13 patients (52%), food 4 (16%). Thirteen subjects were eligible to ASIT and 7 underwent ASIT prior EGPA diagnosis with an average time-to-EGPA of 16.2 years. No statistically significant difference was found in terms of sex, age at diagnosis, positivity or specificity of anti-neutrophil cytoplasm antibodies (ANCA), eosinophil count at onset, clinical manifestations comparing allergic vs. non-allergic, ASIT vs. non-ASIT, ASIT vs. allergic, ASIT vs. eligible.

Conclusions

Among patients with EGPA allergies are highly prevalent, particularly towards inhalants and drugs, often with multiple sensitizations. The absence of correlation between inhalant ASIT exposure and variation in mode and time of EGPA onset doesn’t support the hypothesis of a its potential role in triggering the disease.

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TAKAYASU ARTERITIS AND SACROILIITIS: A CASE CONTROL STUDY IN 28 PATIENTS OF A SINGLE ITALIAN CENTER

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
15:30 - 17:30
Room
HALL F
Lecture Time
16:40 - 16:50
Session Icon
Pre Recorded

Abstract

Background and Aims

A possible shared immunopathogenesis between Spondyloarthritis (SpA) and Takayasu Arteritis (TAK) has been hypothesized and some clinical case aboutSpA in TAK patients has been reported (1). In clinical practice sacroiliitis may be diagnosed by X-ray, CT or MRI.CT findings of sacroiliitis include joint space alterations, joint erosion, subcondral osteoporosis or sclerosis, enthesitis, ankylosis.TAK patients performe routinely FDG-PET/CT for monitoring disease activity.

This study aims to understand if there is an increased incidence of sacroiliitis in TAK patients.

Methods

We collected retrospectively imaging data (CT) of 28 TAK patients and 28 controls (matched for sex and age) undergoing FDG-PET/CT scan. Controls were selected among patients performing FDG-PET/CT in our Nuclear Medicine Unit, excluding patients with bone tumors, bone metastasis and thyroid cancers. An expert rheumatologist read the CT-scans of sacroiliac joints.

Results

No patients or controls demonstrated FDG-uptake in sacroiliac joints.

In the control group we detected sacroiliac sclerosis in two cases: one due to degenerative changes, one to sacroiliitis (1/28, 4%).

In the TAK group four patients presented CT alterations suggestive for sacroiliitis: one bilateral erosion, one bilateral sclerosis, two monolateral sclerosis (4/28, 14%). One of these patients complained an inflammatory back pain.

Conclusions

In our cohort of TAK patients we demonstrated an increased prevalence of sacroiliitis, diagnosed by CT scan. Only one patient reported an inflammatory back pain, while three patients had radiological signs of previous sacroiliitis. This reinforce the need to look for spondyloarthropathy in TAK patients even if asymptomatic.

(1): Guzel Esen S, Joint Bone Spine, 2019

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NEUTROPHIL ELASTASE INHIBITION IS PROTECTIVE IN EXPERIMENTAL MYELOPEROXIDASE ANTI NEUTROPHIL CYTOPLASMIC ANTIBODY VASCULITIS

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
15:30 - 17:30
Room
HALL F
Lecture Time
16:50 - 17:00
Session Icon
Pre Recorded

Abstract

Background and Aims

Neutrophil elastase (NE) is implicated in initiating neutrophil extracellular trap (NET) formation through proteolytic degradation of the nuclear envelope, histone degradation and chromatin decondensation facilitating DNA release. NE bound to NET derived DNA is protected providing a reservoir of proteolytic NE enabling tissue destruction, and further recruitment of neutrophils. This study investigates the pathogenic contribution of NE release through NET formation in experimental myeloperoxidase anti neutrophil cytoplasmic antibody vasculitis (MPO-ANCA) using animals deficient in neutrophil elastase and NE inhibitors.

Methods

A 20 day experimental model of anti-MPO-GN was induced in B6.129X1-Elanetm1Sds/J mice and wild-type (WT) litter mate controls by myeloperoxidase (MPO) immunisation and GN triggered using a sub-nephritogenic dose of anti-glomerular basement membrane globulin. Further experiments using NE inhibitors Alvelestat and BAY 85-8501 given daily by oral gavage was administered to prevent NET formation.

Results

Elane-/- animals were protected from excessive NET production and glomerular injury with significantly reduced kidney proinflammatory gene expression (IL-6, IL-1β, MCP-1 and CXCL2), segmental necrosis, numbers of glomerular neutrophils, extracellular MPO deposition, CD4 T cells, and macrophages influx (all, P <0.05 compared to WT). NE inhibition yielded similar results as seen in the Elane-/- animals. With a significant reduction in the frequency of MPO specific CD4 effector T cells from the draining lymph nodes and a significant reduction in ANCA titre within the serum (P<0.05, compared with WT).

Conclusions

NE inhibition attenuated inflammation through the reduction of pathological NETs. This data provides proof of concept evidence that targeting NE therapeutically may be of potential benefit in MPO-ANCA vasculitis.

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FROM ACTIVE TO NON-ACTIVE: EMPHASIS ON LONGITUDINAL NEUTROPHIL PROFILING IN PATIENTS WITH GIANT CELL ARTERITIS ON CORTICOSTEROID THERAPY IN COMBINATION WITH LEFLUNOMIDE

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
15:30 - 17:30
Room
HALL F
Lecture Time
17:00 - 17:10
Session Icon
Pre Recorded

Abstract

Background and Aims

Monitoring disease activity in patients with giant cell arteritis (GCA) is important, however appropriate biomarkers are lacking. We aimed to define and longitudinally monitor leukocyte subtype profiles, neutrophil expression of adhesion molecules and sera levels of inflammatory parameters.

Methods

Peripheral blood was obtained from therapy-naïve (T0) GCA patients (n=32), at weeks 1, 4, 12, 24 and 48 of follow-up. After T0, the patients received glucocorticoids (GC), with tapering after week 4. Following week 12, 15 patients additionally received leflunomide. For comparison, we included 15 healthy blood donors (HBD). Whole blood samples were analyzed by flow cytometry, while serological parameters were measured by nephelometry, ELISA or MagPix.

Results

GCA patients had lower percentage of CD4+ (p=0.0001), CD8+ (p<0.0001) T-lymphocytes, B-lymphocytes (p=0.0002) and NK cells (p=0.0005) and higher percentage of neutrophils (p<0.0001), with upregulated CD62L (p=0.04), compared to HBD. Neutrophilia persisted during GC therapy, while percentage of lymphoid subsets decreased. Serum amyloid A (SAA; p=0.001), IL-6 (p<0.0001), IL-8, IL-23 and L-selectin were lowered at week 4 and gradually increased by week 12, while IL-18 and anti-cardiolipin antibodies (p=0.0094) declined at weeks 4 and 12, vs. T0. At week 48, SAA (p<0.0001) and IL-6 (p<0.001) remained significantly lower only in patients receiving GC and leflunomide. At weeks 24 and 48, CD11b (p=0.048) and CD62L (p=0.036) were significantly reduced in patients on combinatory therapy, compared to patients receiving only GC.

Conclusions

Neutrophil CD62L and CD11b, together with inflammatory parameters (e.g. SAA, IL-6) could represent an informative panel of biomarkers for GCA activity, additionally lowered by leflunomide.

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MORTALITY AMONG PATIENTS WITH GIANT-CELL ARTERITIS: A LARGE-SCALE POPULATION-BASED COHORT STUDY

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
15:30 - 17:30
Room
HALL F
Lecture Time
17:10 - 17:20
Session Icon
Pre Recorded

Abstract

Background and Aims

Studies regarding mortality among patients with giant-cell-arteritis (GCA) have yielded conflicting results. Thus, in this large population-based study we aimed to examine whether GCA is associated with increased mortality, and if so, the effect of age at diagnosis and gender on the association.

Methods

We utilized the medical database of Clalit-Health-Services for this retrospective cohort study. Follow-up was from January 1,2002 and continued until death or end of follow-up on September 1,2018. Incident GCA patients were compared with age-and-sex-matched controls. Estimated median survival-times were calculated using Kaplan-Meier method. Hazard-ratios for all-cause-mortality were obtained by the Cox proportional-hazard model, adjusted for socio-demographic variables and cardiovascular risk factors.

Results

The study included 7,294 GCA patients and 34,156 controls. The mean age at start of follow-up was 72.1±9.9 years with 69.2% females. Estimated median survival-time was 13.1 years (95% CI, 12.6-13.5 years) in GCA patients compared with 14.3 years (95% CI, 14.1-14.6) in controls (P-value < 0.001).The multivariate analysis demonstrated increased mortality risk in the first 2 years after diagnosis (HR 1.14; 95% CI 1.04-1.2) and >10 years after diagnosis (HR 1.14; 95% CI 1.02-1.3). The mortality-risk was higher in patients diagnosed ≤70 years of age (HR 1.5(95% CI 1.14-1.99) 0-2 years; HR 1.38(95% CI 1.1-1.7) >10 years).

Conclusions

GCA patients have a minor decrease in long-term survival compared to age-and-sex-matched controls. The seen difference is due to excess mortality in the first 2 years, and >10 years after diagnosis. Patients diagnosed ≤70 years of age are at greater risk.

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LARGE VESSEL VASCULITIS: PET/CT RESULTS FROM A LARGE COHORT

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
15:30 - 17:30
Room
HALL F
Lecture Time
17:20 - 17:30
Session Icon
Pre Recorded

Abstract

Background and Aims

18F-FDG PET/CT serves an increasingly important role in the diagnosis of large vessel vasculitis (LVV). By illustrating enhanced uptake in the walls of the aorta and large vessels, PET/CT identifies evidence of active inflammation.

Methods

A retrospective single center study was conducted on patients undergoing 18F-FDG PET/CT scans between 2009 and 2019 at Sheba Medical Center, Israel. The imaging results were analyzed for evidence of LVV.

Results

Out of a cohort of 128 PET/CT studies which were performed, we identified fifty-eight studies which either showed evidence of active vasculitis or were performed in patients who had been previously treated for LVV. In six patients presenting with fevers with no prior diagnoses, PET/CT demonstrated LVV. Out of thirteen PET/CT scans performed in patients with treated LVV, six showed increased large vessel uptake. Eight PET/CT scans showed LVV in patients who had other known inflammatory conditions. Twenty eight of the PET/CT studies showed evidence of LVV as part of malignancy surveillance and three showed LVV in patients with a suspicion for infectious aortitis.

Conclusions

Discussion: The results of the 18F-FDG PET/CTstudies performed illustrate that this modality is useful for identifying inflammation of the large vessels in those patients with a suspicion of LVV. It may also be used to identify active LVV in patients receiving prior treatment. The finding of LVV in the PET/CT's of many patients being surveilled for malignancy relapse reinforces the place of PET/CT, as a critical tool to be used in conjunction with other befitting clinical findings, in diagnosisng LVV.

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