Welcome to the Autoimmunity 2021 Congress Calendar

Background and Aims

50 Million people in the United States suffer from an autoimmune disease, and this number is growing. Up to 70% of cases could be due to environmental factors. Therefore, an understanding of diet, which lends itself intuitively to being a major component of the environmental factors described, merits exploration.

Methods

We sought to develop a system of comparison between human epitopes implicated in seventy autoimmune diseases and the overlap between them and the epitopes found in various commonly consumed animals and plants. The aim of the comparison was to construct a comprehensive database of overlap to provide an index (Gershteyn-Ferreira index) of potential auto-immunogenicity of the various organismal proteins.

Results

The construction of the database utilized the automation of querying and recording the epitopes with the IEDB (Immune Database and Analysis Resource) system. We were able to create a comprehensive index for twenty four organism profiles. Our system personalizes the epitope overlap of the organisms per individual by integrating the human leukocyte antigen (HLA) alleles of the subject and re-running the overlapping epitopes to filter for binding.

Conclusions

With this new system (Immunodietica), we can determine exact epitopes that could be responsible for presence or severity of autoimmune symptoms, as well as a personalized ‘heat-map’ of potential triggers for use by sufferers of autoimmune disorders.

Background and Aims

Autoimmunity affects 50 million people in the United States alone. An estimated 70% of autoimmune disease cases are due to environmental factors. Diet is a risk factor for and modulates the severity of several autoimmune disorders. Yet, interactions between diet and autoimmunity in humans remain largely unexplored, particularly the impact of immunogenetics, i.e. presence of certain human leukocyte antigens (HLA) in individuals, in this interplay. Here, we aimed to systematically interrogate commonly consumed animals and plants for the presence of protein epitopes previously implicated in human autoimmune disorders and determine their tissue expression patterns and binding to autoimmune disease-associated and -protective HLA molecules.

Methods

We aggregated all epitopes implicated in 70 human autoimmune diseases (www.iedb.org) and cross-referenced them with epitopes in 24 organisms. In addition, we annotated the tissue expression pattern of these epitopes and assessed their binding to different HLA alleles in silico.

Results

The species investigated could be divided into three broad categories regarding their content in human autoimmune epitopes, which we represented using a new metric, the Gershteyn-Ferreira index (GF index). Strikingly, pig contains a disproportionately high number of unique autoimmune epitopes compared to all other species analyzed. Interestingly, pig epitopes implicated in multiple sclerosis (MS) were preferentially expressed in nervous tissue and bound to MS-associated HLA alleles.

Conclusions

Immunodietica uncovers a new link between pork consumption and autoimmunity in humans and lays the foundation for future studies on the impact of diet on the pathogenesis and progression of autoimmune disorders.

Background and Aims

Environmental factors have been shown to play a major role in autoimmune diseases; relatively little attention has been given to food components as possible modifiers of these disorders. We summarize the current body of knowledge related to different mechanisms and associations between food components and autoimmunity.

Methods

Because the conformational fit between food antigens and a host’s self-determinants has been determined for only a few food proteins, we used ELISA to examine the reactivity of affinity-purified disease-specific antibodies with different food antigens, and studied the reaction of monoclonal or polyclonal tissue-specific antibodies with various food antigens and the reaction of food-specific antibodies with human tissue antigens.

Results

Our results showed that antibodies made against different tissue antigens react with many food antigens, and food-specific antibodies react with various tissue antigens. For example, Sm-affinity-purified serum from lupus patients reacted strongly with soy, carrot, spinach and corn. Scl70-purified antibody from scleroderma patients reacted with wheat germ, peas, spinach and corn. Thyroid antibody showed strong reaction with 20 out of 204 tested foods, while amyloid-b peptide reacted with 10. Antibody to pancreatic islet cell reacted with many foods. Conversely, milk, corn, soy, egg, peanut, lectins and agglutinins reacted strongly with many tissue antigens.

Conclusions

We postulated that chemical modification of food proteins by toxicants in food may result in immune reaction against modified food proteins that cross-react with tissue antigens, resulting in autoimmune reactivity. Understanding the relationship between specific foods and autoimmunity can assist practitioners to formulate diets that may help prevent or ameliorate autoimmune disease.

Background and Aims

Autoimmune diseases are characterized by chronic inflammation, which causes numerous immune, metabolic and neuroendocrine changes. In the long-run, these perturbations can cause, promote or exacerbate various chronic degenerative conditions, such as dyslipidemia, hypertension, type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease, certain types of cancer, depression, neurodegenerative diseases, endocrine and nutritional disturbances, osteoporosis, sarcopenia, and immunosenescence (which can increase infection risk and impair vaccine responses). Of relevance, several environmental factors are suspected of aggravating or perpetuating the inflammatory state.

Methods

Medline, Embase, Amed, and CINAHL databases were searched for studies reporting on the role of diet and lifestyle in chronic inflammation.

Results

Tobacco smoking, pollution, chronic psychological stress, circadian disruption (caused by shift work, social jet lag, or exposure to artificial light at night), physical inactivity, and the typical hypercaloric, western-type diet (which is high in sugar, refined grains, salt, trans fatty acids, oxidized lipids, and advanced glycation end-products, and low in various micronutrients, fiber, prebiotics, omega-3 fatty acids and phytochemicals), coupled with visceral obesity, increased intestinal permeability and a reduction in microbiota diversity (as a result of increased sanitation, overuse of antibiotics, less time spent in natural spaces and adoption of western-like diets) can promote or exacerbate inflammation. Conversely, various lifestyle and dietary interventions can decrease, inhibit, or resolve inflammation.

Conclusions

We argue that every patient diagnosed with an autoimmune disease should be given lifestyle and dietary recommendations that specifically address inflammation.

Background and Aims

Environmental factors are triggering elements in the development of autoimmune diseases (ADs). High levels of air pollution, especially particulate matter (PM), increase the incidence and severity of ADs. PM is composed of acids, organic chemicals, metals and dust from primary or secondary sources. Nowadays, several studies have shown that PM exposure is associated with type 1 diabetes, rheumatoid arthritis (RA), multiple sclerosis and systemic lupus erythematosus (SLE).

Methods

In vivo and in vitro studies have shown that air pollution can cause an imbalance of T cells, production of pro-inflammatory cytokines, local pulmonary inflammation, oxidative stress and changes in methylation, all these favoring the onset and exacerbation of ADs.

Results

Exposure to diesel exhaust particles seems to be responsible for RA development, at least in genetically susceptible individuals, through the production of IL-18, autophagy, apoptosis, and protein citrullination. PM2.5 levels were associated with anti-dsDNA antibodies in a cohort of SLE patients. In an experimental animal model of Sjögren’s Syndrome (SS), PM exacerbated the pulmonary response. The mice showed lymphocytic peribronchial infiltrates with decreased alveolar space. Likewise, patients with dry eye associated with SS have severe ocular surface abnormalities due to air pollution. Crystalline silica is another component of PM that has shown a strong association with ADs development.

Conclusions

The cellular and molecular mechanisms by which air pollution generate an immune imbalance change according to the physiological interaction and the exposure time. The use of multiple omics techniques will provide solid scientific evidence to understand these mechanisms on the development of chronic diseases.

Background and Aims

Jet-lag may affect air-travellers crossing at least two time-zones. It occurs when the human biological rhythms are out of synch with respect to the day-night cycle at the country destination. Its effect in psoriasis is missing. We aimed to evaluate the effect of Jet-lag in psoriatic patients' management.

Methods

Patients that underwent a flight: patients who experienced jet-lag were compared to patients who did not experience jet-lag. Before the flight, a dermatologist recorded clinical and demographical data with particular attention to Psoriasis Area Severity Index (PASI) and Disease Activity in Psoriatic Arthritis (DAPSA). Patients performed Self-Administered Psoriasis Area Severity Index (SAPASI), the Dermatology Life Quality Index (DLQI) and the pruritus Visual Analog Scale (VAS) scores. After the flight, patients completed the SAPASI, DLQI and pruritus-VAS scores.

Results

The sample recruited comprised of 70 psoriatic patients aged 42.4 ± 9.7 years (median 42.5 years). Thirty (42.9%) were males, mean BMI was 25.5 ± 2.2 kg/m². Average disease duration was 15.2 ± 7.1 years, and 20 (28.6%) subjects had developed PsA. Average hours of flight were 5.4 ± 3.5 (median 3.5 h), with 34 (48.6%) subjects reporting jet-lag. At the multivariate regression analysis, the change in the SAPASI score resulted correlated with jet-lag (regression coefficient 1.63, p = .0092), as well the change in the DLQI score (regression coefficient = 1.73, p = .0009), but no change on the pruritus VAS scale was found.

Conclusions

This study suggests that jet-lag may influence disease severity and DLQI scores, but not itch in psoriatic patients.

Background and Aims

In rheumatoid arthritis (RA) a portion of patients fail to respond to first biological therapy. Predicting the patient’s responsiveness to the first biological therapy is still an unmet medical need. For non-responder patients, this leads to unnecessary exposure, delay of adequate therapy, disease progression and waste of money for the payer as well.

The aim of our study was to identify the selected gene set as genomic biomarkers to predict month 6 therapeutic response to infliximab (IFX), differentiate between good responders and non-responders.

Methods

In the study we enrolled 217 bio-naive RA patients with moderate-high disease activity RA (DAS28-CRP >3.2), who have responded inadequately to DMARDs and assigned to IFX treatment. Developing our in vitro diagnostic test method for the prediction of IFX treatment responsiveness 250 genes were identified by differential gene expression analyses from NGS RNA-Seq data using various machine learning modelling methods, 44 genes were selected which showed significant differences between non-responders and good responders as biomarkers in patient stratification. The expression of this gene set was analyzed using reverse-transcription and quantitative real-time PCR.

Results

Validation clinical studies confirmed that this selected gene set as genomic biomarkers and a proprietary algorithm may predict month 6 therapeutic response to IFX, discriminating between good responders (reached DAS target value DAS28≤3.2 at 6 month) and non-responders.

Conclusions

Our kit received the CE IVD Medical Device Certificate in December 2020, providing a precision medicine tool to personalize IFX therapy.

Background and Aims

Chloroquine derivatives and hydroxychloroquine, which are treatment options in COVID-19, are conventionally used for the treatment and prevention of malaria and for the treatment of autoimmune diseases. Accordingly, this study was initiated by looking for a relation between those.

Methods

Tblastx searches are performed with SARS-CoV-2, by limiting searches to five plasmodium species that infect human.

Presence of aligned sequences in respective organisms' proteomes are searched with blastp.

A 15mer in virus proteome is found to be SARS-CoV-2 query sequence with the highest identity to one plasmodium species. It is searched in the alignments with the other plasmodium species.

Binding of that peptide to MHC class I supertype representatives are predicted. Cytotoxic T lymphocyte epitope predictions is also performed.

Homologous regions with minimum 60% identity to predicted-epitopes in the 15mer are looked for.

Binding strengths of those homologous peptides to previously detected specific MHC class I supertype representative are predicted for homologous sequences.

Results

CFLGYFCTCYFGLFC of SARS-CoV-2 is query sequence with highest identity to P. vivax. It is present in the other plasmodium species' alignments. Its two parts are binding strongly to HLA-A*24:02 . Homologous regions are observed for one, accordingly: Five 10mer peptides in human proteome and twelve 10mer peptides in plasmodium species' proteomes, three of which are predicted to bind strongly to the same allele, in each. Among strong-binder plasmodium peptides, one is homologous to a 10mer in human proteome, which binds strongly to the same allele.

Conclusions

Immune responses to homologous 10mers with strong binding to HLA-A*24:02 may cause autoimmunity.