Welcome to the 13th International Congress on Autoimmunity interactive program

Abstract Body

CD6 is a co-stimulatory receptor, predominantly expressed on T cells, that binds to activated leukocyte cell adhesion molecule (ALCAM), a ligand expressed on antigen-presenting cells and various epithelial and endothelial tissues. T cells are important contributors to the pathogenesis of SLE, especially in the development of kidney disease (lupus nephritis, LN). The CD6-ALCAM pathway plays an integral role in T cell activation, differentiation, proliferation, and trafficking, and increased levels of CD6 are associated with pathogenic T cell responses. Thus, the CD6-ALCAM pathway is a potential contributor to disease pathogenesis and presents itself as a potential therapeutic target. Previously, we showed that soluble ALCAM is increased in urine of LN patients (uALCAM), suggesting that the CD6-ALCAM pathway contributes to disease. To investigate, uALCAM was examined in an extended cohort of 1038 individuals from 5 ethnically-diverse cohorts of patients with SLE and LN; CD6 and ALCAM expression was assessed in LN kidney cells; and disease contribution was tested via antibody blockade of CD6 in murine models of acute glomerulonephritis and SLE. Extended cohort analysis offered strong support for the use of uALCAM as a biomarker that distinguishes active renal involvement in SLE, irrespective of ethnicity. ALCAM was expressed by renal structural cells while CD6 expression was exclusive to T cells, with increased numbers of CD6+ and ALCAM+ cells in LN patients. CD6 blockade in lupus disease models (nephrotoxic serum nephritis; MRL/lpr mice) revealed significant decreases in immune cells, inflammatory markers, and disease measures. Our data are the first to demonstrate the contribution of the CD6-ALCAM pathway to LN and SLE, supporting its use as a disease biomarker and therapeutic target.

Abstract Body

Background and aims: Covid-19 patients often show thyroid function abnormalities. There are no data that patients with autoimmune thyroid disease are more prone to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), nor that they run the risk of developing more severe Covid-19. Therefore, our aim is to deepen out this field.

Methods: We have conducted an observational study that included 515 unselected patients with thyroid disorders by means of telephone survey from April to September 2020. Covid-19 was classified as (1) definite diagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, with an oral/nasopharyngeal swabs test confirmation; (2) highly suspected Covid-19 disease: presence of highly suggestive symptoms, in absence of a swab test.

Results: We observed a significantly higher prevalence of patients with definite diagnosis of Covid-19 disease, or with definite plus highly suspected diagnosis of Covid-19, with respect to “Italian general population”. Moreover, the presence of a definite diagnosis of Covid-19 disease, was significantly higher in patients with thyroid autoimmunity, in comparison to patients with thyroid non autoimmune disorders.

Conclusions: Different thyroid abnormalities are observed in Covid-19 patients. SARS-CoV-2 exploit the angiotensin-converting enzyme 2 expressed in the thyroid gland for docking, entering as well as replication. Thyroid related complications due to Covid-19 infection could be subacute thyroiditis, autoimmune thyroiditis, and an atypical form of thyroiditis. Our data suggest that patients with thyroid autoimmunity should have a higher risk of Covid-19 infection, however larger prospective studies are needed to better investigate this point.

Background and Aims

Myocarditis and inflammatory cardiomyopathy (CMi) are a challenging diagnosis due to the heterogeneity of clinical presentation. Because the clinical course of myocarditis and CMi is unpredictable and the non-invasive diagnostic tests are limited in their ability to make a clear cut diagnosis, all patients with clinically suspected myocarditis and CMi have to undergo endomyocardial biopsy (EMB), before irreversible damage to the myocardium has developed.

Methods

The exact analysis and quantification of intramyocardial inflammation (including lymphocytes, macrophages, cytotoxic cells and cell-adhesion molecules) has been shown to be predictors of the clinical outcome.

Results

Viruses are considered the most common cause of myocarditis and CMi. Persistence of entero/and adenovirus in the myocardium has been associated with ventricular dysfunction and viral genome clearance with improvement of ventricular function. Furthermore, distinct genotypes of erythroviruses including parvovirus B19 and human herpesvirus type 6 (HHV6A/B), among many others, have been identified with varying degrees of frequency in cardiac tissues. Parvovirus B19 with proof of transcriptional activity is associated with poor prognosis.

The effectiveness of anti-viral-therapy has been proven in recent studies, showing that enterovirus/ adenovirus – positive patients benefit from anti-viral therapy with interferon beta-1b.

Myocardial inflammatory processes due to autoimmunity warrant immunosuppressive treatment in order to prevent immune-mediated myocardial injury. Immunosuppression demands biopsy-based exclusion of virus since virus-positive patients do not improve or even deteriorate under anti-inflammatory treatment.

Conclusions

In conclusion, the examination of histology, immunohistology, virology and molecular biology in EMBs is the basis for a rational, causal, personalized and specific therapy.

Background and Aims

Background: Paraneoplastic syndromes may present as autoimmune diseases with atypical presentations in the elderly, or as an exacerbation following a prolonged remission.

Aim: Present a descriptive narrative of a case series of autoimmune disease as the first manifestation of malignancy

Methods

Methods: Patient cases were retrieved from the Wolfson Medical Center database. We reviewed the files for a new onset or flare of autoimmune disease, time to diagnosis and type of malignancy, and survival.

Results

Results: One patient presented with a flare of cicatrial pemphigus following a long-standing remission. She was treated with prednisone with a good response. Some months later, she complained of weight loss, and a whole-body CT revealed lung cancer. The patient died about 18 months from the flare. The second patient presented with a mild flare of SLE after years of remission. Breast cancer was soon diagnosed afterwards. Two years later, following oncologic remission, a second flare again proved to be an oncologic relapse. A third patient was diagnosed with atypical scleroderma sine scleroderma. Initially, a malignancy was not detected. Upon repeated CT, lung cancer was detected 6 months later. The last patient was hospitalized and diagnosed as hypereosinophilic syndrome. The patient only complained of weakness. A whole body CT revealed lung cancer.

Conclusions

Conclusion: A flare after years of remission or an atypical onset of autoimmune disease can be a paraneoplastic syndrome. Close surveillance and repeated imaging are important. Early awareness and detection of a malignancy may be lifesaving.

Background and Aims

Pemphigoid diseases are characterized by autoantibodies against the basement membrane zone (BMZ) of the skin and orifice-close epithelia. MMP has been defined as pemphigoid disease with predominant mucosal lesions. The disease is clinically and immunopathologically heterogenous with mouth and conjunctivae being the most affected sites.

Methods

Lesions outside the mouth tend to heal with scarring leading to visual impairment and finally blindness, as well as, more rarely, impairment of breathing and food intake. Autoantibodies are directed against two main autoantigens, BP180 (collagen type XVII) and laminin 332. BP230, nearly always together with BP180 and, in less than 5%, type VII collagen can also be targeted. Assaying for serum anti-laminin 332 reactivity is pivotal, since in about a quarter of patients with anti-laminin 332 MMP, a malignancy is associated.

Results

Diagnosis is established by the clinical picture with predominant mucosal lesions and visualization of tissue-bound anti-BMZ antibodies by direct immunofluorescence microscopy or detection of serum autoantibodies against the aforementioned antigens.

Conclusions

In recent S3 guidelines initiated by the European Academy of Dermatology and Venereology, the clinical spectrum and diagnostic strategies are detailed. In addition, treatment regimens for different clinical situations including patients with exclusive oral or ocular involvement are outlined.