Welcome to the 13th International Congress on Autoimmunity interactive program
O042 - ECULIZUMAB USE IN CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME (CAPS): DESCRIPTIVE ANALYSIS FROM THE “CAPS REGISTRY” (ID 297)
Abstract
Background and Aims
To describe the real-world experience of eculizumab use in patients with catastrophic antiphospholipid syndrome (CAPS) according to the information provided by the “CAPS Registry”.
Methods
We analyzed the demographic, clinical and immunological data from all the patients included in the “CAPS Registry” treated with eculizumab and described the indications for eculizumab administration, dose, outcome, use of prophylactic vaccines and adverse effects.
Results
The “CAPS Registry” currently includes 584 patients from whom 39 (6.7%) were treated with eculizumab (it was used as a rescue therapy in 30 cases while in 6 cases it was used as first line therapy). Mean age of eculizumab treated patients was 39 years (SD=14.6), 72% were female, 77% had a primary APS and 79% had a precipitating factor before the CAPS event. Thrombocytopenia was present in 28 (72%) cases and features of microangiopathic hemolytic anemia were present in 15 (38.5%). Twenty-nine (74.4%) patients recovered from the episode of CAPS (four showed only partial remission). Symptoms worsened in 9 patients, from whom 5 finally died despite the treatment. There was only one relapse after a median follow up of 10.7 months. The most common treatment regimen was 900 mg weekly for four weeks and 1200mg fortnightly.
Conclusions
According to the real-world experience provided by the “CAPS Registry”, eculizumab can be considered in some patients with CAPS refractory to previous therapies, especially if they present with features of complement-mediated thrombotic microangiopathy.
DOES COVID-19 VACCINATION TRIGGER AUTOIMMUNE RESPONSES? (ID 813)
(AUTO)ANTIBODIES IN COVID-19 AND COVID-19 VACCINATION (ID 814)
IS016 - MULTIPLE SCLEROSIS, COVID-19 AND VACCINES (ID 815)
Abstract
Abstract Body
Disease-modifying therapies (DMTs) for multiple sclerosis (MS) either modulate or suppress the immune system. In patients with MS (PwMS), infection with SARS-CoV-2 and the effects of Covid-19 vaccination are concerns complicated by an increased risk of severe disease in some, and by the effects of DMTs on immune responses to both the virus and the vaccine. We evaluated the effects of DMTs on humoral and cell-mediated immune responses to 2 and 3 mRNA vaccinations and the longevity of SARS-Cov-2 spike IgG levels in 522 PwMS and 68 healthy controls.
Patients treated with most DMTs were seropositive post 2nd and 3rd vaccinations, however only 38% and 44% of ocrelizumab-treated patients and 54% and 46% of fingolimod-treated patients, respectively, were seropositive. IgG levels decreased by 82% within 6 months from 2nd vaccination (p<0.0001), but were boosted 10.3 fold by the 3rd vaccination (p<0.0001), and 1.8 fold compared to ≤3m post 2nd vaccination (p=0.025). Vaccination ≥5 months after ocrelizumab infusion was associated with higher IgG levels (p=0.039 and 0.036 post-2nd and 3rd vaccination), and higher rates of seropositivity. T-cell responses were detected in 89% and 63% of PwMS post 2nd and 3rd vaccination, but in only 25% and 0% of fingolimod-treated patients, while in 100% and 86% of ocrelizumab-treated patients, respectively. We conclude that PwMS treated with most DMTs develop humoral and T-cell responses following 2 and 3 mRNA SARS-CoV-2 vaccinations, however, fingolimod or ocrelizumab blunt humoral responses, while fingolimod compromises also the cellular responses, with no improvement after a 3rd booster.
O043 - IMMUNE MEDIATED EVENTS TIMELY ASSOCIATED WITH COVID-19 VACCINE (ID 23)
Abstract
Background and Aims
Vaccination may induce de novo autoimmune disease, particularly in genetically predisposed individual. We aimed to study cases of new onset immune mediated disease temporally associated with COVID-19 vaccination.
Methods
We analyzed medical records of patients that presented to our secondary/tertiary rheumatology center with rheumatic symptoms developing in association with COVID-19 vaccination.
Results
By the Aug/2021, around 361,000 residents in our region received at least one dose of COVID-19 vaccines available in the country (Pfizer-BioNTech and Moderna, Oxford/AstraZeneca and Jannsen/Johnson&Johnson). During the same period, we identified 28 adults in whom the onset of (auto)immune disease was timely associated with vaccination. Vasculitis was the most prevalent (9 cases), followed by polymyalgia rheumatica, skin panniculitis and neuromuscular disorders. (Table 1) Patients developed symptoms with a median (IQR) delay of 10 (7 – 18) days after either partial (12 cases), or full (16 cases) vaccination. Interestingly, two patients recovered 6 months prior to vaccination from COVID-19, and another one finished a full vaccination during proven COVID-19. Three patients had a history of rheumatic disease, that was in complete remission at the time of vaccination. Overall, 25 patients received systemic treatment (glucocorticoids 23; NSAID 1; anticoagulants 4; DMARD 2), two local treatment (surgery 1, local steroids 1), and one patient received no treatment.
Conclusions
COVID-19 vaccines should be considered as a risk factor for inducing autoimmune and autoinflammatory phenomena.
O044 - MYOCARDITIS FOLLOWING COVID-19 VACCINATIONS: A SYSTEMIC REVIEW (ID 217)
Abstract
Background and Aims
Early reports following the FDA approval of COVID-19 vaccines suggested an association between the vaccines, mainly mRNA-based, and myocarditis. The side effect was considered as the most hazardous and notorious side effect. In fact, myocarditis most commonly arises following a viral infection, and although rare, it can occur following vaccination as well. There are several potential mechanisms behind this phenomenon, all share the same principle of hyper-immunity resulting in the activation of pro-inflammatory and immunological mechanisms in the myocardium, resulting in the signs and symptoms of the disease.
Methods
In our review, we performed an extensive literature review, utilizing PubMed and Google Scholar search engines in the years 2020-2022 regarding myocarditis and COVID-19 vaccines. All vaccination types reviewed; however, the focus was on mRNA-based vaccines. Baseline characteristics of the different studies, time from vaccine to myocarditis diagnosis, the current knowledge regarding the pathogenesis, and management were all addressed.
Results
An increase in the incidence of myocarditis among vaccinated versus unvaccinated patients was seen in several large-scale studies. Negative PCR tests in some of the studies suggested myocarditis was not induced by SARS-CoV-2 infection. The highest incidence reported was following the second dose of the vaccine, either with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines, in young male patients, and was mild to moderate in severity. Cardiac function was restored within several weeks and management was mainly conservative
Conclusions
There is a slight increase in the incidence of myocarditis following COVID-19 vaccination. The pathogenesis seems to be mediated by hyper-immunity.
O045 - DETECTION OF AUTOANTIBODIES GENERATED AFTER SARS-COV2 VACCINATION USING ENGINE PROTEIN ARRAYS (ID 403)
Abstract
Background and Aims
Background and aims: Since December 2019, the spread of COVID-19, developed into a health challenging worldwide pandemic. COVID-19 is an acute respiratory disease, initiated by SARS-CoV-2. In response to this pandemic, development of different gene-based vaccines was fast driven. They encode the SARS-CoV-2-spike protein for induction of neutralizing antibodies against the receptor-binding-domain. This desired vaccination-induced seroconversion could be accompanied by generation of autoantibodies in vaccinated persons.
Methods
Methods: Sera from 11 individuals, vaccinated against SARS-CoV-2, were studied before (T0) and up to 17 weeks (T5) after 1. vaccination. Screening was performed using engine array 1008 (15.000 human proteins; expression host: E.coli), to identify autoantibodies induced by vaccination. 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: For all T5 samples autoantibody-candidates, not detectable in corresponding T0 samples, were found. In total 222 hits were identified, representing 180 genes. For 13 antigens signals could be confirmed in 3 (33%), for 37 in two different donors (20%). For genes detected in at least two individuals, a search for disease associations was performed. For 7 proteins (31%) correlated disorders (e.g. cardiology, autoimmunity, neoplasms) were described but for 50% no published associations are available.
Conclusions
Conclusion: engine protein arrays offer high potentials for detection of novel autoantibodies induced by vaccination against SARS-CoV-2. Every follow-up serum sample showed formerly absent antibodies. Clinical relevance of candidates must be confirmed in larger sample cohorts with different timepoints and subsequent functional testing.
O046 - AUTOIMMUNE HEMOLYTIC ANEMIA AFTER COVID-19 VACCINATION: A ONE YEAR CASE REVISION IN A CLINICAL AUTOIMMUNE LABORATORY (ID 405)
Abstract
Background and Aims
Coronavirus 2019 disease (COVID‐19) is still ongoing two years after the beginning of this pandemic. COVID 19 early vaccination development was one of the most challenging scientific breakthroughs of all mankind. Although major disease complications are now coming to our clinical settings, early post vaccination autoimmune manifestations have caught our eye mainly concerning hematological diseases like autoimmune hemolytic anemia and immune thrombocytopenic purpura. Other autoimmune diseases like thyroiditis, Kawasaki disease, Guillain‐Barre syndrome, as well as other autoantibody detection has revealed the potential of COVID‐19 in inducing autoimmune response.
Methods
We revised 4 cases of autoimmune hemolytic anemia in older patients following early vaccination period with mRNA vaccine, focusing in vaccination time frame, hemolytic markers and clinical manifestations.
Results
All of our patients had preexisting conditions, and although disease was time limited, it was not mild, as they all required hospitalization for hemodynamic and proinflammatory response control.
Conclusions
Autoimmune hematological disorders after COVID-19 vaccines should come into our mind as some patients may have higher risk of thrombotic complications. Monitoring of blood counts and early hemolytic markers as well as patient education are key for early diagnosis and management.
O047 - CAN THE ANTI-SARS-COV-2 VACCINATION BOOST AUTOANTIBODY PRODUCTION IN PATIENTS WITH TRIPLE POSITIVITY FOR ANTIPHOSPHOLIPID ANTIBODIES? (ID 445)
Abstract
Background and Aims
The role of anti-SARS-CoV2 vaccines in autoantibodies’ induction has not been well established. This study aims to evaluate the potential induction of autoantibodies after anti-SARS-CoV2 vaccination in a triple positive antiphospholipid (aPL) cohort.
Methods
Eighteen subjects were enrolled (M/F= 17/1; median age=52 years; 5 PAPS, 5 SLE-associated APS, 8 aPL carriers). Serum samples were collected before the first (T0) and at least one month after the second administration (T1) of anti-SARS-CoV2 vaccination. A wide panel of autoantibodies was evaluated through routinely methods.
Results
None developed additional autoimmune signs/symptoms upon vaccination. Patients majority did not display new autoantibody positivity (table 1). Changes were observed in 3 patients: 1) one aPL carrier ANA negative at T0 became ANA positive with homogenous pattern at T1 (negative anti-dsDNA and anti-ENA); this patient was actually ANA positive in her clinical history; 2) one aPL carrier patient affected by SLE, who was IgM and IgG aCL and IgG aβ2GPI positive at T0, turned positive for IgM and IgA aβ2GPI; 3) one aPL carrier patient affected by Behçet Disease, who was positive for IgM aCL and IgM aβ2GPI at T0, turned positive for IgA aCL and IgA aβ2GPI. All emerging aPL were low titre.
Conclusions
Anti-SARS-CoV2 vaccination did not induce clinical signs of autoimmunity in our cohort. Autoantibodies serology remained mostly stable. Few patients experienced the emergence of low titre aPL, possibly as an expected inter-assay variation rather than an evolving “serological flare”.
O048 - NOVEL SPIKE/NUCLEOCAPSID WHOLE BLOOD T CELL INTERFERON GAMMA RELEASE ASSAY TO EVALUATE SARS-COV2 AND COVID19 VACCINE T CELL MEMORY RESPONSES IN PATIENTS WITH AUTOIMMUNE DISEASES. (ID 273)
Abstract
Background and Aims
Develop a routine whole blood interferon gamma release assay (IGRA) remains mandatory to study SARS-Cov2-specific memory T cell responses in immunocompromised individuals such as those with autoimmune diseases, the aim of the study.
Methods
Preliminary experiments were initiated to evaluate different Spike T cell response in twenty volunteers vaccinated with BNT162b2 using different platforms (ELISpot, IGRA, recombinant proteins or peptides). Next, 103 non-vaccinated healthy individuals and 70 samples from individuals having received COVID19 vaccine including 20 non-Sars-Cov2 infected patients with autoimmune/immunodeficiency diseases (e.g. SLE, SEP, GCA…) were tested for T cell and humoral responses.
Results
First, full length recombinant proteins rather than peptides were selected to develop a whole blood IGRA assay for routine. Next and following COVID19 vaccination, anti-Spike antibodies response (100% in healthy vs 71.4% in patients) and IGRA-Spike T cell response (98% in healthy vs 61.9% in patients) took place as compared to non vaccinated individuals that presented a SARS-Cov2 infection rate around 10% (IGRA-nucleocapsid and/or IgG anti-nucleocapsid). Among the autoimmune/immunodeficiency disease group, steroids rather than biologics (e.g. rituximab, tocilizumab…) affect the cellular response before and after the third/fourth vaccine boost. Within the healthy group, COVID19 vaccine humoral response decreases first (>100 days) followed by the cellular response (>200 days), which can be reversed following vaccine boost.
Conclusions
This ongoing study confirms the utility of the IGRA-Spike/-nucleocapsid assay coupled with serology in COVID19 vaccinated individuals and in particular in those immunocompromised such as patients with autoimmune diseases treated with steroids.
O049 - AUTOIMMUNE NEUROLOGICAL MANIFESTATIONS FOLLOWING COVID-19 VACCINES (ID 205)
Abstract
Background and Aims
We aimed to present the autoimmune neurological manifestations of the side effects of COVID-19 vaccinations as the following pathologies:
Methods
Guillain-Barre syndrome, an autoimmune neurological disease leading to acute flaccid paralysis. While there is some evidence of increased incidence of GBS following the ChAdOx1-S/nCoV-19 (AstraZeneca) vaccine, it is still unclear whether GBS occurs following the BNT162b2 and mRNA-1273 (Pfizer and Moderna) vaccines. According to the UK Health Security Agency the risk of developing GBS after the first dose of AstraZeneca vaccine adds 5.6 extra cases of GBS per million doses, while having no association to the second dose. Transverse myelitis, an immune mediated damage to spinal cord, resulting in paralysis, sensory alterations, and autonomic dysfunction. A rare subtype of longitudinally extensive transverse myelitis began to emerge from case reports following AstraZeneca vaccine. Most cases occurred in patients under 60 years of age who presented with neurological symptoms starting within 3 weeks of the first dose of the vaccine. Regarding transverse myelitis after the Pfizer vaccine, two patients developed acute transverse myelitis, with a rate of 0.28 per 100,000 cases. Furthermore, only very few cases have been reported after receiving the Moderna vaccine.
Results
Bell’s palsy, a unilateral facial paralysis was reported following Pfizer vaccine. A review of published literature failed to identify case reports of isolated Bell’s palsy linked to the AstraZeneca vaccination.
Conclusions
Conclusion: Neurological adverse effects of COVID-19 vaccination are a rarity. However, further investigation and documentation is needed, especially regarding GBS after the first dose of AstraZeneca vaccine.
O050 - B AND T CELL RESPONSES TO VACCINATION ARE DIFFERENTLY AFFECTED BY B-CELL TARGETED THERAPIES IN SYSTEMIC AUTOIMMUNE DISEASES. (ID 558)
Abstract
Background and Aims
Patients with rheumatic diseases are at higher risk of severe outcome when infected by SARS-CoV2 and vaccination is strongly recommended. However, immunosuppressive therapies can impair response to vaccine. Therefore, we have evaluated B and T-cell mediated immune response to mRNA vaccination in patients with connective tissue diseases or ANCA vasculitis under continuous treatment with B-cell targeted therapies.
Methods
Twenty-eight consecutive patients under treatment with rituximab (RTX, n. 11) or Belimumab (BLM, n.17) and 13 age/sex matched controls (non-rheumatic healthcare personnel) were enrolled in the study. Nobody presented anti-SARS-CoV2 antibodies related to previous viral contact and all were always negative at the molecular swab monthly control. All patients and controls received mRNA vaccines and were tested three to four weeks after complete vaccination. All RTX patients started vaccination within 5 months from the last infusion, and all but one of them were B-cell depleted. Anti-SARS-CoV-2 RBD antibodies were analysed by a diagnostic assay (Elecsys, Roche) while T-cell response was evaluated using the IGRA test (Euroimmun).
Results
Detectable anti-SARS-CoV2 RBD antibodies were documented in 1/11 RTX patients versus 16/17 BLM patients. The median concentration was significantly lower than that observed in controls (39.6 AU/ml vs 1133 AU/ml, p=0.002). The IGRA test was positive in 8/11 (72.7%) RTX patients vs 16/17 (94.1%) BLM patients, with interferon release comparable to control subjects.
Conclusions
B cell targeted therapies significantly affect B-cell response to vaccination, especially RTX. In contrast, in a large percentage of patients, T cell response was as efficient as in controls.