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Displaying One Session

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

SMALL FIBER NEUROPATHY AND AUTOIMMUNITY

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
10:00 - 12:00
Room
HALL F
Lecture Time
10:00 - 10:20
Presenter
Session Icon
Pre Recorded

ATYPIC POSTTRANSLATIONALLY MODIFIED AUTOANTIGENS AS IMMUNOGENIC DRIVERS OF B-CELL-NEOPLASMS

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
10:00 - 12:00
Room
HALL F
Lecture Time
10:20 - 10:30
Session Icon
Pre Recorded

Abstract

Background and Aims

Approximately 90% of lymphoma originate from B cells. Several entities depend on chronic BCR activation. For most lymphomas BCR-target antigens are unclear. As atypic posttranslational modifications represents a potential mechanism to generate immunogenicity, we included posttranslationally modified proteins in our screening antigens of lymphoma BCRs.

Methods

BCR-expression cloning was performed from cryopreserved lymphoma specimen and established cell lines encompassing diffuse large B cell lymphoma (DLBCL), primary central nervous system lymphoma (PCNSL), Burkitt lymphoma and mantle cell lymphoma (MCL). Recombinant BCRs were screened on several types of protein arrays, including posttranslationally modified arrays. Target antigens were analyzed proteomically and functionally.

Results

For MCL LRPAP1 was identified as a frequent lymphoma BCR antigen (8 /21 patients + Z138 and MAVER1 lines). For PCNSL SAMD14/neurabin-I werre identiefied as target in 8 of 12 patients and both were hyper-N-glycosylated (ASN339 for SAMD14; ASN1277 for Neurabin-I). For DLBCL Ars2 was a frequent BCR target (8/20 patients and U2932, OCI-Ly10 and OCI-Ly3 lines) and Ars2 was hypophosphorylated. For sporadic Burkitt lymphoma acetylated HSP40 and sumoylated Bystin were antigens of two specific cell lines. In all these lymphoma entities, clear and strong humoral immune responses, i.e. high-titered autoantibodies against these antigens were detectable. Addition of the antigens to the respective cell lines activated the BCR pathway and inducted proliferation. Vice versa addition of immunotoxins encompassing the epitope of the BCR target antigen fused to Pseudomonas aeruginosa Exotoxin A were specifically toxic to cell lines with the respective lymphoma BCR.

Conclusions

Posttranslationally modified autoantigens play an early and crucial role in lymphomagensis.

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ANTI-CARBAMYLATED PROTEINS ANTIBODIES LEVELS AS PREDICTOR OF CLINICAL RESPONSE TO ABATACEPT IN RHEUMATOID ARTHRITIS.

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
10:00 - 12:00
Room
HALL F
Lecture Time
10:30 - 10:40
Session Icon
Pre Recorded

Abstract

Background and Aims

Carbamylation is a post-translational modification of proteins. It was demonstrated that the 16% of anti-citrullinated proteins antibodies (ACPA) negative rheumatoid arthritis (RA) patients had a positivity for anti-carbamylated proteins antibodies (anti-CarP). This study was focused to verify whether anti-CarP antibodies can be used as a predictive factor of abatacept response (ABA).

Methods

Sixty patients (F/M=49/11; media(±standard deviation) of age=57(±12.1)years; CRP(C Reactive Protein)-DAS28=4.59(±0.99); ACPA positive (n (%))=51(85); RF positive=35(58)), ABA treated were enrolled. ELISA-test for anti-CarP IgG and a commercial anti-CCP3.1 kit (Inova Diagnostic) for ACPA IgG were applied. Rheumatoid Factor (RF) (Siemens) was also tested.

Results

At baseline, the 30% of patients were anti-CarP positive. They were younger (p=0.01) with a longer disease duration (p=0.05) and with higher CRP levels (p<0.05), when compared to anti-CarP negative. A significant reduction of anti-CarP titre after twelve-months of treatment was shown (p<0.01) with a reduction of CRP-DAS28 in the first six months of therapy in anti-CarP positive patients (p=0.03). No significant results were found by dividing the cohort using the positivity to ACPA and/or RF.

Conclusions

The precocious onset and a longer disease duration in anti-CarP positive patients might suggest them as a risk factors for RA in this subgroup of patients. The link between the anti-CarP positivity at baseline and the reduction of disease activity during the first six months of treatment let us to hypothesize that anti-CarP antibodies, but not ACPA and/or RF, could be a predictive factor of a good clinical response to ABA.

Shi J, PNAS USA 2011;Trouw LA, Autoimmun Rev 2012.

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AGE-ASSOCIATED IGD-CD27- DOUBLE NEGATIVE (DN) B CELLS WITH A PRO-INFLAMMATORY PHENOTYPE AND FUNCTION ARE ABNORMALLY ELEVATED IN MULTIPLE SCLEROSIS PATIENTS

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
10:00 - 12:00
Room
HALL F
Lecture Time
10:40 - 10:50
Session Icon
Pre Recorded

Abstract

Background and Aims

Age-associated IgD-CD27-double negative (DN) B cells have been described in autoimmunity. We aimed to investigate the prevalence and functions of DN B cells in MS patients.

Methods

Peripheral blood frequencies of DN B cells and their expression of costimulatory and antigen presentation molecules were determined in healthy controls (HC) and MS patients using flow cytometry. DN B cells were also measured in paired blood and cerebrospinal fluid of MS patients. Cytokine production was analysed following ex vivo B cell stimulation. DN B cell migration was studied using an in vitro chemotaxis assay. The T-box transcription factor T-bet, previously described in a pathological age-associated B cell subset, was measured in DN B cells.

Results

DN B cells were significantly elevated in the peripheral blood of MS patients younger than 60 years compared with age-matched HC (p=0.004), and were further increased in MS cerebrospinal fluid (p=0.03). Expression of antigen presentation and costimulatory molecules CD80/CD86 on DN B cells indicated their potential to induce T cell responses. DN B cells produced pro-inflammatory lymphotoxin-α, tumor necrosis factor-α and granzyme B and demonstrated high migration towards the pro-inflammatory chemokines CXCL10 and CXCL13. T-bet expression was found in 22[3.3, 52.0]% of MS DN B cells.

Conclusions

Thus, DN B cells are abnormally elevated in MS patients and could migrate into the central nervous system. They could contribute to inflammation by induction of T cell responses and pro-inflammatory cytokine production. Further research on DN B cells could lead to novel targets for more specific MS therapy.

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CD27 DIFFERENTIALLY REGULATES TREG AND TH17 CELLS DURING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS (EAE)

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
10:00 - 12:00
Room
HALL F
Lecture Time
10:50 - 11:00
Session Icon
Pre Recorded

Abstract

Background and Aims

CD27/CD70 costimulation enhances T-cell survival, expansion and Th1-effector function. However, in (RORγt+)Th17 cells, CD27 signalling reduces activation by suppressing IL-17 production. Consequently, CD27KO mice have more IL-17 producing cells compared to WT mice and display exacerbated EAE. Modulating this pathway might therefore be a promising approach to treat Th17-cell mediated diseases. However, (RORyt+)Foxp3+ regulatory T (Treg) cells, which are crucial for suppressing Th17 autoimmunity, might also be affected.

Methods

To examine how CD27 costimulation affects (RORyt+)Treg vs. Th17 cells, we used a MOG-induced EAE mouse-model and studied the effect of absence (CD27KO) or over-stimulation (CD70tg) of CD27.

Results

Single-cell mRNA-sequencing of CNS-infiltrating cells confirmed enhanced activation and survival of Th17 cells in the absence of CD27. However, in Treg cells from CD27KO mice, OX40 and 4-1BB, markers important for Treg-cell activity/stability, were down-regulated. Furthermore, the frequency of RORyt+Treg cells was significantly reduced in the CNS and these Treg cells expressed lower levels of Bcl-2. Over-stimulation of CD27 could invert this phenotype suggesting that CD27 is required for Treg survival/activation in the inflammatory environment. Furthermore, Treg cells in the periphery of CD27KO mice expressed less CCR6 during an early phase of the disease suggesting delayed CNS-homing.

Conclusions

Based on this, we believe that Th17 and Treg cells are differentially regulated by CD27 during EAE: stimulating CD27 may suppress Th17-cell activation/survival while enhancing activation, survival and CNS homing of Treg cells. Thus, modulating CD27/CD70 costimulation presents a promising approach to tip the Th17/Treg balance towards Treg activity.

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ASSIGNING LIKELIHOOD RATIOS TO IMMUNOBLOT ASSAY RESULTS: A CLINICAL APPROACH IN AUTOIMMUNE REPORTING

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
10:00 - 12:00
Room
HALL F
Lecture Time
11:00 - 11:10
Session Icon
Pre Recorded

Abstract

Background and Aims

Recent studies showed how using likelihood ratios (LRs) to report autoantibodies results may improve their clinical interpretation. We aimed to assess whether LR calculation could be extended to antibodies to anti-extractable nuclear antigens (ENA) tests results, carried out by immunoblot (IB).

Methods

We evaluated result specific LRs for the ENA profile (Sm, RNP, Ro60, Ro52, Scl70, Jo1 and CENP-B) by an immunodot method (BlueDiver Quantrix, D-tek, Belgium) on 269 diagnostic samples from patients with ANA-associated autoimmune rheumatic diseases (AARD) [systemic lupus erythematosus (SLE) (n=79), primary Sjögren’s syndrome (SjS) (n=97), systemic sclerosis (SSc) (n=69), idiopathic inflammatory myositis (IIM) (n=12), mixed connective tissue disease (MCTD) (n=12)], and samples from 117 controls (81 diseased controls and 30 healthy blood donors).

Results

We calculated the LRs for each single anti-ENA antibody and for all antibodies grouped together, defining LR at different thresholds (Table). At 6 arbitrary units (AU) (corresponding to the cutoff indicated by the manufacturer), 12 AU, 25 AU, and 50 AU (corresponding to assay calibrators), overall positive LRs (all antibodies grouped together) for AARD were 14.5, 16.0, 41.2 and 65.0, respectively, while overall negative LRs for AARD were 0.45, 0.47, 0.54 and 0.62, respectively.

table-.png

Conclusions

Our study shows that expressing results in LR is also feasible using IB methods, even if some differences may be found due to local variation in the referred population. The use of LRs in addition to antibody values may facilitate the clinical interpretation of anti-ENA IB results and may contribute to harmonizing autoimmune laboratory reporting.

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ANKYLOSING SPONDYLITIS AND RISK OF SKELETAL MANIFESTATIONS: A MATCHED-COHORT STUDY

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
10:00 - 12:00
Room
HALL F
Lecture Time
11:10 - 11:20
Session Icon
Pre Recorded

Abstract

Background and Aims

Background: The risk incurred by ankylosing spondylitis (AS) for developing osteoporosis, hip fracture, and the necessity for a joint replacement remains unknown.

Aims: To estimate the hazard for osteoporosis, hip fractures, and joint replacement in patients with AS compared to controls.

Methods

Methods: This was a retrospective cohort study. It was based on the chronic disease registry of Clalit Health Services that covers over 4.4 million patients from cradle to grave and draws data from primary care clinics, outpatient clinics, hospitals, and pharmacies. All patients diagnosed with AS between 2002 and 2018 were included—patients with one of the outcomes prior to AS diagnosis were excluded. Controls were matched by sex, date of birth, socioeconomic status, and country of birth in a 5:1 ratio. Cox regressions were used.

Results

Results: Overall, 5,930 AS patients were diagnosed during the study period. Of them, 5,352 were free of the investigated outcomes prior to the AS diagnosis. Matching resulted in 27,404 controls. Of the final cohort, 64% were men, 63% born in Israel, 28% of low socioeconomic status, with a mean age of 49 (17) at the time of AS diagnosis, and a mean follow-up of 7.8 years. AS patients had adjusted hazard ratios of 1.83 (1.58-2.11) for osteoporosis, 1.53 (1.23-1.89) for hip fractures, 2.26 (1.96-2.60) for joint replacement, and 1.20 (1.11-1.31) for mortality.

Conclusions

Conclusion: AS increases the risk of osteoporosis, hip fracture, joint replacement, and death. Our study implies that active screening and attempts for prevention should be considered in this high-risk population.

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DEVELOPMENT AND EVALUATION OF I-TRACKER VEDOLIZUMAB AND I-TRACKER ANTI-VEDOLIZUMAB KITS: FAST AND INNOVATIVE CHEMILUMINESCENT ASSAYS FOR THE MONITORING OF PATIENTS TREATED WITH VEDOLIZUMAB

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
10:00 - 12:00
Room
HALL F
Lecture Time
11:20 - 11:30
Session Icon
Pre Recorded

Abstract

Background and Aims

Therapeutic Drug Monitoring is currently proposed to provide useful information to clinicians to improve the efficacy of the treatment. Theradiag developed the innovative i-Tracker Vedolizumab and i-Tracker Anti-Vedolizumab kits: fast quantification of Vedolizumab and Anti-Vedolizumab antibodies fully automated on the random access i-Track10 chemiluminescent analyzer.

Methods

Analytical performances were assessed using 2 types of serum samples: human serum spiked with Vedolizumab or Anti-Vedolizumab antibodies, and samples from IBD patients treated with Vedolizumab (n=33). Vedolizumab from serum sample was captured by anti-idiotypic antibody coupled magnetic microparticles and anti-Vedolizumab polyclonal antibodies conjugated to acridinium ester were used for the detection of Vedolizumab. Anti-Vedolizumab antibodies were captured according to Vedolizumab coupled magnetic microparticles and detected with the use of Vedolizumab conjugated to acridinium ester.

Results

Vedolizumab measurement showed high accuracy (recovery was comprised between 84% and 108%). High precision was reached for both assays (intra-precision CV were below 3.5% and 3.5% for Vedolizumab and Anti-Vedolizumab assays; inter-precision CV were below 6.1% and 4.4% respectively). No interference was seen with biologic agents (bilirubin, hemoglobin, lipids, biotin and rheumatoid factors). The dynamic ranges of the assays were 1µg/ml to 60µg/ml for Vedolizumab quantification and 10 ng/ml to 2000 ng/ml for anti-Vedolizumab antibodies quantification. i-Tracker assays showed excellent correlation with LISA-TRACKER assays (R² = 0.96, Slope = 0.91 for Vedolizumab assay; Spearman’s coefficient correlation was 0.84 for Anti-Vedolizumab assay).

Conclusions

i-Tracker kits are innovative assays which exhibit fast, accurate and reproducible results for the quantification of Vedolizumab and Anti-Vedolizumab antibodies. Excellent agreements were observed with respective LISA-TRACKER assays

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THYROID AUTOIMMUNITY AND COVID-19 INFECTION, REVIEW OF THE LITERATURE, AND REPORT OF A LARGE ITALIAN SERIE.

Session Type
PARALLEL SESSIONS
Date
30.05.2021, Sunday
Session Time
10:00 - 12:00
Room
HALL F
Lecture Time
11:30 - 11:50
Session Icon
Pre Recorded