Welcome to the 13th International Congress on Autoimmunity interactive program

Displaying One Session

Date
Tue, 28.02.2023
Session Time
14:30 - 16:30
Room
NIKOS SKALKOTAS
Session Type
PARALLEL SESSIONS

LEADERSHIP IN THE COVID-19 EPIDEMIC AND VACCINATION ROLLOUT (ID 801)

Date
Tue, 28.02.2023
Session Time
14:30 - 16:30
Session Type
PARALLEL SESSIONS
Room
NIKOS SKALKOTAS
Lecture Time
14:30 - 14:55

IS010 - COVID-19 AND HASHIMOTO’S DISEASE (ID 800)

Date
Tue, 28.02.2023
Session Time
14:30 - 16:30
Session Type
PARALLEL SESSIONS
Room
NIKOS SKALKOTAS
Lecture Time
14:55 - 15:05

Abstract

Abstract Body

COVID-19 and autoimmune thyroiditis (AIT) often are comorbid because of high prevalence of both entities and possible viral induction of autoimmunity. Molecular mimicry of viral and self antigens is one of the key factors in autoimmunity promotion. We studied correlative dynamics of ferritin level and few immunoendocrine parameters in people with AIT who suffered from COVID-19 and explored possible molecular mimicry of SARS-CoV2 and human thyroid antigens. 409 AIT patients were involved, 214 of them suffered from COVID-19 (23 patients were examined during the acute phase of COVID-19, and 191 - 1 to 18 months after negative PCR test achieved). Clinical blood analyses, serum levels of ferritin, TSH, freeT4, freeT3, prolactin, cortisol, and autoantibodies (Aab) towards thyroglobulin, thyroperoxidase and TSH receptors were measured. We also performed a bioinformatic analysis of probable pentapeptide sharing between human thyroid antigens and SARS- CoV-2 spike glycoprotein, based on UNIPROT and NCBI databases with use of Python language. The level of ferritin in individuals with AIT who did not suffer from COVID-19 fluctuated within the normal range with a tendency to its lower limit and inversely correlated with prolactin (r=-0.11). Ferritin level reflected the severity of COVID-19, especially lung damage. Blood lymphocyte absolute count and relative % in acute COVID-19 decreased with subsequent normalization. This can be related to emigration of lymphocytes from the blood to the involved tissues during acute COVID-19 and may play a part in multi-organ postcovid autoimmune disorders. Ferritin strongly positively correlated with Aab to TSH receptors (r=0.82); less strongly – with hemoglobin (r=0.47), and weakly – with body mass index (r=0.23), fT3 (r=0.13), and iron levels (r=0.07). Bioinformatic study revealed 6 pentapeptides common for thyroid autoantigens and SARS-CoV-2 (P0DTC2) spike glycoprotein, shown in table 1 below:

Thyroid autoantigens

Shared pentapeptides

Thyroglobulin (P01266)

FNFSQ, SAIGK, LDSKT

Thyrotropin receptor (P16473)

ICGDS, LLPLV

Thyroid peroxidase (P07202)

RAAEI

Hide

O024 - IDENTIFICATION OF AUTOANTIBODIES IN LONG-COVID PATIENTS BY ENGINE HEALTHY ALIGNMENT (ID 424)

Date
Tue, 28.02.2023
Session Time
14:30 - 16:30
Session Type
PARALLEL SESSIONS
Room
NIKOS SKALKOTAS
Lecture Time
15:05 - 15:20

Abstract

Background and Aims

Background and aims: Protein arrays are a powerful tool to identify autoreactive proteins in clinical samples for various disorders. But the achieved data must be validated by comparison with reference samples of healthy and self-reported healthy donors. Engine developed the ENGINE HEALTHY ALIGNMENT for search on potential autoantibodies. This new database can be applied for identification of autoantibodies in patients of various disorders. Here, samples of Long-Covid patients were used as clinical application model.

Methods

Methods: Human sera from healthy donors (20) and patients with previous SARS-CoV-2 infection and long term clinical symptoms were screened using engine array 1008 (15.000 human proteins; expression host: E.coli), to identify autoantibodies in healthy individuals in comparison to SARS-CoV-2-induced autoantibodies. After incubation of diluted sera, detection was performed using anti-human-IgG-AP-secondary antibody. Signals were declared positive if comparable signal intensities for duplicate clones were distinguishable from background.

Results

Results: ENGINE HEALTHY ALIGNMENT was successfully used to identify autoreactive proteins in Long-Covid patients. For healthy reference cohort positive and negative signal should be found in the majority of analyzed samples. For pathological samples, possible candidates of reactive autoantibodies were only considered if protein arrays showed positive signals for one target protein in at least 2 different donor serums.

Conclusions

Conclusion: The availability of a valid reference cohort is crucial for fast and reliable identification of pathological candidates. The inclusion of sufficient data of healthy controls and comparison of this data with different clinical projects will be the base for reliable identification of disease related autoantibodies.

Hide

O025 - AUTOANTIBODY PROFILES ASSOCIATED WITH POST-ACUTE SEQUELAE OF COVID-19 (ID 508)

Date
Tue, 28.02.2023
Session Time
14:30 - 16:30
Session Type
PARALLEL SESSIONS
Room
NIKOS SKALKOTAS
Lecture Time
15:20 - 15:35

Abstract

Background and Aims

After the acute phase of COVID-19 infection, many individuals experience persistent symptoms known as post-acute sequelae of COVID-19 (PASC). Long-term symptoms vary considerably, ranging from enduring anosmia to neurocognitive deficits, and may cause considerable disability and suffering. Although the underlying and likely diverse causes of PASC remain unknown, pre-existing or new-onset autoantibodies are major hypotheses. Therefore, we aim to analyze the autoantibody repertoire in 800 extensively clinically characterized healthcare workers (HCW) followed over 3-5 visits, spanning 8-16 months of the pandemic.

Methods

In the initial phase of the study, we have analyzed 32 HCW with long-term symptoms on two sets of in-house developed planar protein arrays. The untargeted array contains 42000 protein fragments representing approximately 18000 human proteins, while the targeted array contains 1500 full-length secreted or extracellular proteins representing the human secretome.

Results

Early analyses indicate 150 detected autoantibodies on the untargeted (Fig.1A) and targeted (Fig.1B) arrays, with 20 being shared between the long-term symptom groups. In addition, 130 autoantibodies are group-specific, illustrating the breadth of autoantibody responses in COVID-19. The most prevalent autoantibody anti-CFHR2 was found in 6/8 symptom groups, and anti-IFNA and anti-IFNGR IgG were found in single groups, corroborating previous findings.
p12.png

Conclusions

We have revealed 150 shared and unique autoantibodies in HCW with different symptoms of PASC. These autoantibodies, together with previously internally and externally reported autoantibodies, are currently undergoing extensive longitudinal analysis using bead arrays with the aim to associate autoantibodies with SARS-CoV-2 infection onset and clinical outcomes. Results from this analysis will be presented in Athens.

Hide

O026 - POST COVID OR LONG COVID: WHAT HAVE WE LEARNED UNTIL NOW? (ID 207)

Date
Tue, 28.02.2023
Session Time
14:30 - 16:30
Session Type
PARALLEL SESSIONS
Room
NIKOS SKALKOTAS
Lecture Time
15:35 - 15:45
Presenter

Abstract

Background and Aims

The long period of time needed to recover from COVID-19 and the continuation, or the appearance of new complaints, have evolved into a new notion addressing both subjective and objective findings in patients following the recovery from SARS-CoV-2 infection.

Methods

Post COVID or long COVID, have been used interchangeably to describe this period of time. In fact, the persistence of symptoms following infections is not per se a new finding; however, as SARS-CoV-2 and COVID-19 have emerged as a pandemic affecting hundreds of millions around the world, the burden that resulted from the pandemic in terms of the numbers of recovered patients with various complaints, and medical referrals due to the symptoms, necessitates a solid and consensus-like approach as well as a treatment plan for the symptoms of the recovery period.

Results

For this to happen, a clear illustration of the symptoms and organ-related complaints together with possible causes need to be addressed. Interestingly, particularly as SARS-CoV-2 causes a respiratory illness, almost all body systems were reported to have part in the post COVID syndrome.

Conclusions

While neurologic and neuropsychiatric sequelae drew a lot of attention; cardiovascular, renal, and ocular manifestations were reported. The wide distribution of angiotensin-converting enzyme 2 (ACE2) receptors, responsible for viral entry were suggested as a mechanism. Nevertheless, hematogenous spread, central nervous system (CNS) invasion, and intestinal dysbiosis were shown to play a role as well. Therefore, we aimed hereby to review the recent data regarding the manifestations of the post COVID syndrome alongside suggested pathogenetic explanations.

Hide

O027 - SEVERE COVID-19 SHARES A COMMON NEUTROPHIL ACTIVATION SIG-NATURE WITH OTHER ACUTE INFLAMMATORY STATES. (ID 961)

Date
Tue, 28.02.2023
Session Time
14:30 - 16:30
Session Type
PARALLEL SESSIONS
Room
NIKOS SKALKOTAS
Lecture Time
15:45 - 16:00

Abstract

Background and Aims

Severe COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we investigated the transcriptome of 1596 individuals, including patients with COVID-19 in comparison to healthy controls, other acute inflammatory states (HLH, multisystem inflammatory syndrome in children [MIS-C], Kawasaky disease [KD]), and different respiratory infections (seasonal coronavirus, influenza, bacterial pneumonia).

Methods

We compared the molecular overlap between patients with COVID-19 and those with HLH, defined the transcriptomic and proteomic signatures stratifying COVID-19 severity, and then investigated the behavior of the resulting molecular signature in other inflammatory syndromes and infectious diseases.

Results

We observed that COVID-19 and HLH share immunological pathways (cytokine/chemokine signaling and neutrophil-mediated immune responses), including gene signatures that stratify COVID-19 patients admitted to the intensive care unit (ICU) and COVID-19_nonICU patients. Of note, among the common differentially expressed genes (DEG), there is a cluster of neutrophil-associated genes that reflects a generalized hyperinflamatory state since it is also dysregulated in patients with KD and bacterial pneumonia. These genes are dysregulated at protein level across several COVID-19 studies and form an interconnected network with differentially expressed plasma proteins that point to neutrophil hyperactivation in COVID-19 patients admitted to the ICU. scRNAseq analysis indicated that these genes are specifically upregulated across different leukocyte populations, including lymphocyte subsets and immature neutrophils.

Conclusions

COVID-19 and HLH show a common dysregulated neutrophil-associated gene signature that reflects a generalized hyperinflamatory state and associates with COVID-19 severity.

Hide

O028 - ASSOCIATION BETWEEN COVID-19 VACCINATION AND AUTOIMMUNE BULLOUS DISEASES: A SYSTEMATIC REVIEW (ID 772)

Date
Tue, 28.02.2023
Session Time
14:30 - 16:30
Session Type
PARALLEL SESSIONS
Room
NIKOS SKALKOTAS
Lecture Time
16:00 - 16:10

Abstract

Background and Aims

An association between COVID-19 vaccination and autoimmune bullous diseases (AIBDs) has been suggested, but no systematic evaluation exists to corroborate this assumption.

Methods

A systematic literature review focusing on this potential link was performed.

Results

Electronic searches using PubMed from inception to February 2022 identified 30 reports meeting predetermined inclusion and exclusion criteria. Among 932 immunized individuals, patients either presented clinically with de novo AIBDs (n = 53; 5.7%) or had a flare/worsening of pre-existing AIBDs (n = 91; 9.7%) after vaccination, whereas vaccination did not negatively influence the clinical course in 788 (84.5%) patients. The reported time between receiving the first or second dose of the vaccine and manifestation of AIBDs ranged between 1 day and 6  weeks, with some patients experiencing aggravation of their AIBD symptoms after the second dose. The clinical courses of post-vaccinal AIBDs were mostly well controlled with conventional immunosuppressive therapy.

Conclusions

While causality between COVID-19 vaccination and AIBDs remains unproven and should not affect present vaccination recommendations for this group of patients, raised awareness and timely recognition of rare post-SARS-CoV-2-vaccinal cases would be important for their optimal management.

Hide

O029 - COVID-19 AND IMMUNOLOGICAL DYSREGULATION: ROLE OF ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ID 721)

Date
Tue, 28.02.2023
Session Time
14:30 - 16:30
Session Type
PARALLEL SESSIONS
Room
NIKOS SKALKOTAS
Lecture Time
16:10 - 16:20

Abstract

Background and Aims

Coronavirus disease 2019 (COVID-19) is characterized by different manifestations, including an immune system imbalance. However, the specific mechanism that triggers a dysregulated immune response is not yet completely known.AntiNeutrophil Cytoplasmic Antibodies (ANCAs) are autoantibodies directed against various neutrophil antigens, including MyeloPerOxidase (MPO) and PRoteinase 3 (PR3). The current study investigated the potential usefulness of anti-MPO and anti-PR3 to elucidate whether the infection stimulates autoantibody production and contributes to autoimmunity activation in COVID-19 patients.

Methods

We assessed 110 patients hospitalized for COVID-19, 62 (interquartile range [IQR], 52-72) years, admitted to COVID-19 Units at the University Hospital “P. Giaccone” of Palermo, Italy. Hematological, biochemical, and inflammatory parameters were evaluated. ANCA testing (anti-MPO and anti-PR3) was analyzed using a chemiluminescent assay (ACL AcuStar; Instrumentation Laboratory).

Results

Laboratory results revealed a reduction in lymphocytes, higher levels of C Reactive Protein (CRP) and IL-6. In the great majority (76%) a moderate decrease in vitamin D levels was found. In addition, a weak increase in serum D-dimer and high-sensitive troponin T (hs-TnT) concentrations were observed in 37% and 51% of patients. Our analysis showed that anti-MPO and anti-PR3 antibodies were present in <2% and <5%, respectively, of study population.

Conclusions

It has been known that SARS-CoV-2 can trigger a strong immune response in some individuals. Our results don't show greater activation of autoimmune response given the low rate of ANCAs positivity encountered. However, the study is ongoing for a long-term evaluation of patients and to understand a better clinical utility of autoimmunity in monitoring in association with other laboratory tests.

Hide

O030 - THE RELATIONSHIP BETWEEN AUTOANTIBODIES TARGETING GPCRS AND RAS-RELATED MOLECULES ASSOCIATES WITH COVID-19 SEVERITY (ID 336)

Date
Tue, 28.02.2023
Session Time
14:30 - 16:30
Session Type
PARALLEL SESSIONS
Room
NIKOS SKALKOTAS
Lecture Time
16:20 - 16:30

Abstract

Background and Aims

The coronavirus disease 2019 (COVID-19) can manifest features resembling systemic autoimmune diseases, including the presence of autoantibodies that are still poorly characterized. Here we aimed to perform a cross-sectional study of 246 individuals to determine whether autoantibodies targeting G protein-coupled receptors (GPCRs) and renin-angiotensin system (RAS)-related molecules associate with the clinical severity of COVID-19.

Methods

We assessed the serum levels of these autoantibodies in patients with COVID-19 versus healthy controls.

Results

Patients with moderate and severe disease exhibited higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Machine learning classification identified anti-GPCR autoantibodies targeting the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as having the strongest association with disease severity. Moreover, while the autoantibody network signatures were relatively conserved in patients with mild COVID-19 relative to healthy controls, they were disrupted in patients with moderate disease severity and even more disrupted in patients with severe disease.

Conclusions

Our results are in line with our previous work showing that anti-GPCR antibodies are natural components of human biology that become dysregulated in inflammatory and autoimmune diseases, suggesting novel molecular pathways for therapeutic intervention in COVID-19 patients.

Hide