Welcome to the 13th International Congress on Autoimmunity interactive program

Abstract Body

Children with autoimmune inflammatory rheumatic diseases (AIIRD) may have an increased risk of infections due to the disease itself or to treatment with immunosuppressive drugs. Adolescents with AIIRD can be at-risk for disease flare secondary to COVID-19 infection, and to withholding their anti-inflammatory therapy. Therefore, it is crucial to prevent COVID-19 disease in this population.

Understanding the impact of COVID-19 infection on children and young people with AIIRD is important for informing national protection, school attendance and vaccination guidance. A large, cooperative, multinational study found that most children and young people with AIIRD experience mild COVID-19 disease. However, hospitalizations did occur, mainly among those with SLE/MCTD, vasculitis, and rare autoinflammatory syndromes.

The socioeconomic burden of COVID-19 and pressure on healthcare systems can only be alleviated by achieving herd immunity against SARS-CoV-2. Vaccines can lead to this objective. Patients with pediatric-onset AIIRD require a personalized vaccination schedule that considers many factors, including disease activity, treatment, infection risk, and vaccine safety and efficacy.

In continuation of the positive findings of Covid vaccines in adults with AIIRD, an international, prospective, multicenter study demonstrated safety and immunogenicity of the BNT162b2 anti-SARS-CoV-2 vaccine among adolescents and young adults with juvenile-onset AIIRD, including those on immunosuppressive therapy. The seropositivity rate was 97.3% in the AIIRD group compared with 100% among controls. However, anti-S1/S2 antibody titers were significantly lower in the AIIRD group, similar to adults with AIIRD.

We will present, for the first time, results of the effectiveness of the BNT162b2 mRNA COVID-19 vaccine among adolescents with AIIRD. By using a very large dataset from the largest healthcare organization in Israel, we conducted an observational cohort study, demonstrating that the BNT162b2 mRNA vaccine is highly effective in adolescents with AIIRD, similar to healthy controls. Immunosuppressive therapy did not affect effectiveness.

PRES recommends vaccinating pediatric rheumatology patients against COVID-19 using vaccines approved by relevant national health authorities.

Our results and those of other studies demonstrating safety, immunogenicity, and effectiveness, together can make the PRES statement stronger and encourage adolescents with AIIRD to get vaccinated against COVID-19, which will help decrease the global burden of the disease.

Background and Aims

Basophils are clearly implicated in allergy, but recent experimental evidence supported their immunoregulatory role even in autoimmunity, especially in systemic lupus erythematosus (SLE). Initial studies suggested that circulating basophils can be reduced in adult patients with SLE. No studies investigating basophil homeostasis in pediatric SLE (pSLE) are available: here, we investigated this aspect in this specific population.

Methods

Three groups of pediatric patients (pSLE; Juvenile Idiophatic Arthritis, JIA; children affected with non-rheumatic/inflammatory disorders, nRHE) have been investigated. Circulating basophils were assessed through flow cytometry. Briefly, basophils were identified as FceRI+ and CCR3+ peripheral blood mononuclear cells (PBMC). The statistical analysis was performed by one-way ANOVA.

Results

Fifty-five pediatric patients were included in this study: pSLE (n=20; 13.3±2.1 years; F/M=3/17), JIA (n=18; 13.5±2.7 years; F/M=9/9), and children admitted to the pediatric inpatient department for non-rheumatic/non-inflammatory chronic disorders (nRHE, n=17; 12.5±3.2 years; F/M=9/8). JIA patients were classified in different ILAR subtypes; nRHE children included: type 1 diabetes mellitus, hypopituitarism, Turner syndrome, short stature, osteogenesis imperfecta. Basophils number were expressed as number per 500,000 PBMC. In general, patients with pSLE (895±751) showed a statistically significant reduction of basophil numbers compared to children affected with another rheumatic disorder (JIA: 2,111±728; p<0.001) or different non-rheumatic chronic diseases (2,353±978; p<0.001).

Conclusions

No matter the clinical characteristics, disease activity and stage, and ongoing therapy, patients with pSLE seems to have a statistically significant reduction of circulating basophils than children with JIA or non-rheumatic/non-inflammatory conditions. The physiopathological and clinical significance of this finding is unclear; further clinical studies and multi-parametric analysis are required.

Background and Aims

The objective of this study was to establish pediatric reference limits for autoimmune disease markers in the CALIPER cohort of healthy children and adolescents to support their interpretation. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) is a national study of healthy children aiming to close gaps in pediatric laboratory medicine by establishing a robust database of pediatric reference intervals for pediatric disease biomarkers (caliperdatabase.org).

Methods

Healthy children and adolescents (n=123), aged 1-19 were recruited as part of the CALIPER study with informed consent. Serum autoantibody testing was conducted using chemiluminescent immunoassays on the BIO-FLASH automated analyzer (Biokit, Barcelona, Spain) including anti-dsDNA IgG, anti-Sm IgG, anti-RNP IgG, anti-SSB/La IgG, anti-Ro60 IgG, anti-Ro52 IgG, anti-cardiolipin IgG, anti-MPO IgG, anti-PR3 IgG, and anti-tTG IgA. Pediatric reference limits representing the 95^th, 97.5^th, and 99^th percentiles were calculated using the non-parametric rank method according to Clinical Laboratory Standards Institute C28-A3 guidelines.

Results

The proportion of samples with results above the assay reportable range were: anti-dsDNA (26/119; 22%), anti-Sm (16/121; 13%), anti-RNP (1,120; 0.8%), anti-SSB/La (0/120; 0%), anti-Ro60 (0/122, 0%), anti-Ro52 (0/121, 0%), anti-cardiolipin IgG (105/117, 90%), anti-MPO (29/118, 25%), anti-PR3 (11/119, 9%), and anti-tTG IgA (34/120, 28%). Pediatric reference limits and associated 90% confidence intervals were established for all 10 markers and found to be below the manufacturer’s assay cut-offs.

Conclusions

Robust pediatric reference limits for 10 commonly clinically utilized autoimmune markers established herein will allow for improved laboratory assessment of pediatric patients using this assay platform worldwide.

Background and Aims

Lupus nephritis (LN) is a leading cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). T cells are strongly implicated in the mechanisms of LN disease. CD6 is a receptor on T cells, that binds to ALCAM, a ligand expressed on antigen presenting cells and tissues. The CD6-ALCAM pathway plays an integral role in modulating T cell activation and trafficking and is central to immune-mediated inflammation. Previously, we reported that soluble urine ALCAM is a potential biomarker in LN. Here, we evaluated the correlation of serum and urine ALCAM and CD6 with disease activity over time.

Methods

Serum and urine samples were obtained from patients with LN (n=345) and living kidney donor controls (n=68). Longitudinal sampling (3, 6, and 12 months) was available for 143 LN patients. ALCAM and CD6 levels were quantified and analyzed cross-sectionally and longitudinally against disease measures that included proteinuria, SLEDAI, renal SLEDAI, and ISN-RPS histological class of the lesion.

Results

Consistent with our previous findings, urinary ALCAM was significantly elevated in LN patients (mean 4333.5 pg/mL) compared to control subjects (mean 214.4 pg/mL), while there were no differences in serum ALCAM levels. Serum and urine levels of CD6 did not change with disease activity, suggesting that these differences are not due to hemodynamic changes or loss of glomerular permeability. In patients followed with longitudinal sampling, urinary ALCAM reflected changes in SLEDAI and R-SLEDAI.

Conclusions

Hence, we show that urinary ALCAM levels are elevated in SLE patients with active LN and decline with clinical improvement.

Background and Aims

CD6 is a co‐stimulatory receptor predominantly expressed on T cells; its ligand, ALCAM, is expressed on antigen presenting cells, as well as epithelial/endothelial cells. Itolizumab is a humanized IgG1 monoclonal antibody which binds CD6 to inhibit T cell activation and trafficking.

Methods

EQUALISE is an open-label Phase 1b two‐part study evaluating the safety, PK/PD, and clinical activity of two subcutaneous itolizumab doses two weeks apart (0.4 to 3.2 mg/kg). Part A enrolled adult patients with active or inactive SLE who received at least one prior SLE treatment. Part B of the study, which doses subjects (1.6mg/kg Q2W) with active proliferative Class III/IV lupus nephritis for 24 weeks, is currently enrolling (NCT04128579).

Results

Part A enrolled 35 subjects in 5 cohorts: 0.4 mg/kg (n=6), 0.8 mg/kg (n=7), 1.6 mg/kg (n=7), 2.4 mg/kg (n=6), and 3.2 mg/kg (n=9). Similar baseline characteristics were noted across cohorts. Subcutaneous dosing of cohorts 1‐4 (0.4 mg/kg through 2.4 mg/kg (N=26)) was well tolerated. For Cohort 5 (3.2mg/kg), >85% of subjects reported an AE, most commonly an injection site reaction, mainly moderate grade 2 (patients received at least 2 separate injections per dose). Among 6 patients with baseline UPCR > 200mg/g (mean 378mg/g), a geometric mean decrease in UPCR of 42% was observed on Day 57 (greater decline seen in subjects with higher baseline UPCR values).

Conclusions

Two subcutaneous doses of itolizumab up to 2.4 mg/kg SC in SLE subjects were well tolerated with reduced tolerability in the 3.2 mg/kg cohort with 50% of patients discontinuing after the first dose.

Background and Aims

Subacute thyroiditis is a post-inflammatory thyroid disease presenting with pain, fever and hyperthyroidism. Thyroid disease is a rare manifestation of SARS-CoV-2 infection. Cases of subacute thyroiditis in patients with the Covid-19 infection, have been described. Vaccination against the SARS-CoV-2 virus has helped to limit the pandemic and is characterized by very few side effects. Amongst those, subacute thyroiditis and Graves’ disease have been observed.

Methods

A case of a female 50-year old patient is presented who developed subacute thyroiditis 2 months after a mild SARS-CoV-2 infection. The case of a 53-old male patient who developed subacute thyroiditis 3 days after vaccination against the SARS-CoV-2 virus is also presented. Both patients had high CRP and ESR and low TSH levels.

Results

Prednisolone was administered 16 mg twice daily for 10 days with subsequent tapering and propranolol 20 mg twice daily. Remission of the disease was observed in both cases. In the female patient the disease recurred one month after prednisolone withdrawal.

Conclusions

Cases of subacute thyroiditis after SARS-CoV-2 infection and after vaccination against the SARS-CoV-2 virus are described. SARS-CoV-2 is a coronavirus which has been related to the development of autoimmunity. Autoimmune thyroid disease, in the form of either subacute thyroiditis, autoimmune thyroiditis and Graves’ disease have been described in patients with the Covid-19 disease.