3^rd International Conference on Autoimmunity November 26-27, 2018 Dublin, Ireland (Louis Fitzgerald Hotel)

Biography:

José Moreno is an MD from the National University of Mexico, with clinical training in Rheumatology and PhD in Immunology with major focus on immunobiology of antigen processing and autoimmunity. He did two postdoctoral trainings in Dallas (Southwestern Medical College) and Heidelberg (Deutsches Krebsforschungszentrum). He has published over 50 papers in international peer-reviewed journals and his currently the Director of Research of Hospital Juárez de México. He is a Member of the National Academy of Medicine (Mexico).

Abstract:

Introduction: Genome-wide association studies have identified many loci associated to autoimmune diseases, but the roles of particular genes are unknown.

Materials & Methods: Global gene expression analysis of healthy (C57BL/6-J and Balb/c-J), and autoimmune (MRL^lpr/lpr) mice was achieved on immunocompetent cell mRNA by means of Affymetrix Chip Mouse 430_2. Data from Affymetrix-TAC were normalized by Robust Multi-array Average (RMA) and differentially-expressed genes (DEG) identified by Limma (FDR <0.001, fold change >3). Gene-grouping analysis was achieved by WebGestalt 2017 online using Bonferroni correction through over representation analysis (ORA) for gene ontology (GO) for biological process and molecular function (non-redundant). For pathways, Reactome or Kegg were used and phenotype analysis by mammalian phenotype ontology.

Results: ORA: GO yielded 151 significant biological processes (immune system process -133 DEG, FDR=0-, immune response -91 DEG, FDR=0-, regulation of immune system process -76 DEG, FDR=3.19E-10-, among others); and two molecular functions (cytokine activity, hydrolase activity). Pathways identified by Reactome were eight (neutrophil degranulation -39 DEG, FDR=1.34E-3-, immune system -82 DEG, FDR=4.72E-2-, innate immune system -62 DEG, FDR=4.72E-3-) and three by Kegg (complement and coagulation cascades (-12 DEG, FDR=1.15E-2). Interestingly, phenotypes identified several abnormal immune system functions, including autoimmune disease, with many DEG. Data were also analyzed by GSEA through GO, which again yielded many biological processes by Reactome and Kegg as 37 and 25 pathways, respectively. Notable DEG included IFNG, CD28, TNFRSF9, C3AR1, C5AR1, CFI, CTLA4, IL-8 and other chemokines, MAP kinases, Padi4, etc.

Conclusions: The results indicate that autoimmune disease in MRL^/lpr mice rises from a complex immune network activation with a featuring role of T cells and costimulatory receptors.

Biography:

Xianming Mo is a Professor of Internal Medicine and acts as Director of Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, and West China Hospital, Sichuan University. He obtained his Medical Degree from North Sichuan Medical College. He was then trained in Pathology and Master of Medicine in West China University of Medical Sciences. After obtaining a PhD Degree in Peking Union Medical College, he moved to Humboldt-Universität zu Berlin and then to Medical College of Georgia as a Postdoctoral Fellow. Then, he became a Junior Faculty in Medical College of Georgia and Senior Scientist in Max Delbrück Center for Molecular Medicine. In 2006, he returned back to West China Hospital.

Abstract:

The purpose of this study was to visualize the difference of immune cellular compositions in peripheral blood of patients with systemic lupus erythematosus (SLE) and healthy controls. Immune cells in the peripheral blood were obtained from 32 SLE patients and 16 healthy subjects. Circulating granulocytes, basophils, dendritic cells (DCs), monocytes, T cells, B cells, natural killer (NK) cells, CD127⁺ innate lymphoid cells (ILCs) and their subpopulations were identified by flow cytometry. The frequencies of T cells, CD4⁺ T cells, T regulatory cells (Tregs), CD127⁺CD8⁺ T, CD56⁺CD8⁺ T, CD25^hi B cells, NK cells, CD16⁺ NK, CD16^bright CD56^dim NK cells and CD127⁺ ILCs were decreased in SLE compared to healthy controls, while the proportion of granulocytes, CD8⁺ T cells, CD25⁺ DN T cells, CD16^- NK, CD16^-CD56^dim NK cells and CD4⁺CD127⁺ ILCs elevated in SLE. High expression of HLA-DR was identified on T cell subsets in SLE patients. Besides, the expressions of HLA-DR, CD11c and CD25 were higher on CD56^dim and CD56^bright NK cells in SLE. The proportion of B cells was negatively related with serum C3/C4 level, and was higher in the patients with anti-ribosomal (Rib) antibody positive. The frequency of CD25⁺CD56^bright NK was positively related with SLE disease activity index 2000 (SLEDAI-2k), and CD16⁺ NK cells was positively related with immunoglobulin G (IgG) while CD16^- NK cells was negatively correlated with IgG. Additionally, the frequency of CD127⁺CD8⁺ T cells was higher in the patients with mucocutaneous manifestations and in the patients with anti-ribonucleoprotein (RNP) antibody positive. The proportion of HLA-DR⁺CD56^bright NK cells was lower in the patients with the presence of anti-Sjögren’s-syndrome-related antigen A (SSA) antibody. Besides, the proportion of CD16⁺CD8⁺ T cells was higher in the patients with presence of Coombs test. A comprehensive peripheral immunophenotypic analysis including myeloid cells and lymphoid cells was performed and diverse abnormalities and alterations of peripheral immune cells were found in SLE patients.

Biography:

Hella Kohlhof is the CSO and Co-founder of Immunic AG. She studied biology in Aachen, Gothenborg (Sweden) and Munich and received her Doctorate in Biology from the LMU in Munich (Germany). During her Ph.D. and PostDoc at the at the Helmholtz Centre in Munich, she worked in the field of immunology and oncology. In 2008 she joined 4SC AG as group leader for translational pharmacology. From 2011 on, Hella was responsible for the management and development of one epigenetic clinical stage small molecule inhibitor and from 2015 on, as Director Development Projects, responsible for the complete development portfolio of 4SC AG.

Abstract:

IMU-838 is an orally available small molecule inhibitor of Dihydroorotate Dehydrogenase (DHODH). It is currently in placebo-controlled phase 2 clinical testing in patients suffering from ulcerative colitis. Further clinical trials are planned in Crohn’s disease and Multiple Sclerosis. DHODH is the key enzyme for de novo pyrimidine synthesis. Activation of DHODH ensures immediate and increased nucleotide supply for RNA and DNA synthesis, when the salvage pathway for pyrimidine synthesis is not sufficient. Pyrimidine de novo synthesis and DHODH activity is only important in metabolically activated cells, e.g. autoreactive immune cells. Therefore, this small molecule inhibitor targeting DHODH is per se selective on overreacting immune cells but is not immunosuppressive in general. This is a huge advantage for the long-term treatment of chronic inflammatory diseases like Multiple Sclerosis and inflammatory bowel diseases. Treatment with immunosuppressive drugs often causes reactivation of latent viruses leading to serious infections and with sometimes even lethal outcome. With IMU-838, Immunic Therapeutics develops a potent and safe oral drug with a unique mode of action for the treatment of chronic inflammatory diseases.     

Biography:

Johan Frostegård is a Professor of Medicine since 2003 and Senior Consultant in Internal Medicine and in Rheumatology. His research is focused on Autoimmunity and Atherosclerosis, where his research group has for the first time identified a novel protection marker, natural antibodies against phosphorylcholine (anti-PC) and also mechanisms which could provide a cause as to how anti-PC could protect against both autoimmunity and atherosclerosis. He led a European Union research consortium, CVDIMMUNE, where some of the concepts developed were presented.

Abstract:

Background: Atherosclerosis is a chronic inflammatory disease process, which leads to cardiovascular disease (CVD) which is increased in rheumatic diseases, especially in systemic lupus erythematosus (SLE). IgM antibodies to phosphorylcholine (anti-PC) constitute a significant part of the circulating IgM pool. We reported that anti-PC is a protection marker for atherosclerosis and CVD, and applies also to rheumatic and autoimmune diseases.

Material & Methods: We use a combination of ex vivo studies and cohort studies. Dendritic cells (DC) and T cells from patients with SLE, and from atherosclerotic plaques, are studied, and anti-PC is determined by ELISA.

Results: Having low levels of anti-PC (below tertile or quartile) was associated with SLE, with CVD and atherosclerosis in SLE, and with being a non-responder to biologics in rheumatoid arthritis. Anti-PC promoted polarization of T cells from SLE patients into T regulatory cells, and from a lower level than among controls, T regs normalized in SLE patients after anti-PC exposure. Other potential underlying mechanisms include an anti-inflammatory property (inhibition of pro-inflammatory lipids which are raised in SLE); inhibition of uptake of oxidized LDL in macrophages; increased clearance by phagocytosis of dead cells. Anti-PC levels were very high in New Guinea among people living a traditional “stone age” life, and where rheumatic diseases and chronic inflammatory conditions are virtually unknown and also anti-PC was associated with some infectious agents there.

Conclusion: Low anti-PC could contribute to development of autoimmune and rheumatic disease, in addition to atherosclerosis and CVD. One underlying cause could be lack of exposure to some microorganisms. These findings could have therapeutic implications, including immunization to raise anti-PC levels.

Biography:

Xianming Mo is a Professor of Internal Medicine and acts as Director of Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, and West China Hospital, Sichuan University. He obtained his Medical Degree from North Sichuan Medical College. He was then trained in Pathology and Master of Medicine in West China University of Medical Sciences. After obtaining a PhD Degree in Peking Union Medical College, he moved to Humboldt-Universität zu Berlin and then to Medical College of Georgia as a Postdoctoral Fellow. Then, he became a Junior Faculty in Medical College of Georgia and Senior Scientist in Max Delbrück Center for Molecular Medicine. In 2006, he returned back to West China Hospital.

Abstract:

The purpose of this study was to visualize the difference of immune cellular compositions in peripheral blood of patients with systemic lupus erythematosus (SLE) and healthy controls. Immune cells in the peripheral blood were obtained from 32 SLE patients and 16 healthy subjects. Circulating granulocytes, basophils, dendritic cells (DCs), monocytes, T cells, B cells, natural killer (NK) cells, CD127⁺ innate lymphoid cells (ILCs) and their subpopulations were identified by flow cytometry. The frequencies of T cells, CD4⁺ T cells, T regulatory cells (Tregs), CD127⁺CD8⁺ T, CD56⁺CD8⁺ T, CD25^hi B cells, NK cells, CD16⁺ NK, CD16^bright CD56^dim NK cells and CD127⁺ ILCs were decreased in SLE compared to healthy controls, while the proportion of granulocytes, CD8⁺ T cells, CD25⁺ DN T cells, CD16^- NK, CD16^-CD56^dim NK cells and CD4⁺CD127⁺ ILCs elevated in SLE. High expression of HLA-DR was identified on T cell subsets in SLE patients. Besides, the expressions of HLA-DR, CD11c and CD25 were higher on CD56^dim and CD56^bright NK cells in SLE. The proportion of B cells was negatively related with serum C3/C4 level, and was higher in the patients with anti-ribosomal (Rib) antibody positive. The frequency of CD25⁺CD56^bright NK was positively related with SLE disease activity index 2000 (SLEDAI-2k), and CD16⁺ NK cells was positively related with immunoglobulin G (IgG) while CD16^- NK cells was negatively correlated with IgG. Additionally, the frequency of CD127⁺CD8⁺ T cells was higher in the patients with mucocutaneous manifestations and in the patients with anti-ribonucleoprotein (RNP) antibody positive. The proportion of HLA-DR⁺CD56^bright NK cells was lower in the patients with the presence of anti-Sjögren’s-syndrome-related antigen A (SSA) antibody. Besides, the proportion of CD16⁺CD8⁺ T cells was higher in the patients with presence of Coombs test. A comprehensive peripheral immunophenotypic analysis including myeloid cells and lymphoid cells was performed and diverse abnormalities and alterations of peripheral immune cells were found in SLE patients.

Biography:

Hella Kohlhof is the CSO and Co-founder of Immunic AG. She studied biology in Aachen, Gothenborg (Sweden) and Munich and received her Doctorate in Biology from the LMU in Munich (Germany). During her Ph.D. and PostDoc at the at the Helmholtz Centre in Munich, she worked in the field of immunology and oncology. In 2008 she joined 4SC AG as group leader for translational pharmacology. From 2011 on, Hella was responsible for the management and development of one epigenetic clinical stage small molecule inhibitor and from 2015 on, as Director Development Projects, responsible for the complete development portfolio of 4SC AG.

Abstract:

IMU-838 is an orally available small molecule inhibitor of Dihydroorotate Dehydrogenase (DHODH). It is currently in placebo-controlled phase 2 clinical testing in patients suffering from ulcerative colitis. Further clinical trials are planned in Crohn’s disease and Multiple Sclerosis. DHODH is the key enzyme for de novo pyrimidine synthesis. Activation of DHODH ensures immediate and increased nucleotide supply for RNA and DNA synthesis, when the salvage pathway for pyrimidine synthesis is not sufficient. Pyrimidine de novo synthesis and DHODH activity is only important in metabolically activated cells, e.g. autoreactive immune cells. Therefore, this small molecule inhibitor targeting DHODH is per se selective on overreacting immune cells but is not immunosuppressive in general. This is a huge advantage for the long-term treatment of chronic inflammatory diseases like Multiple Sclerosis and inflammatory bowel diseases. Treatment with immunosuppressive drugs often causes reactivation of latent viruses leading to serious infections and with sometimes even lethal outcome. With IMU-838, Immunic Therapeutics develops a potent and safe oral drug with a unique mode of action for the treatment of chronic inflammatory diseases.

Biography:

Johan Frostegård is a Professor of Medicine since 2003 and Senior Consultant in Internal Medicine and in Rheumatology. His research is focused on Autoimmunity and Atherosclerosis, where his research group has for the first time identified a novel protection marker, natural antibodies against phosphorylcholine (anti-PC) and also mechanisms which could provide a cause as to how anti-PC could protect against both autoimmunity and atherosclerosis. He led a European Union research consortium, CVDIMMUNE, where some of the concepts developed were presented.

Abstract:

Background: Atherosclerosis is a chronic inflammatory disease process, which leads to cardiovascular disease (CVD) which is increased in rheumatic diseases, especially in systemic lupus erythematosus (SLE). IgM antibodies to phosphorylcholine (anti-PC) constitute a significant part of the circulating IgM pool. We reported that anti-PC is a protection marker for atherosclerosis and CVD, and applies also to rheumatic and autoimmune diseases.

Material & Methods: We use a combination of ex vivo studies and cohort studies. Dendritic cells (DC) and T cells from patients with SLE, and from atherosclerotic plaques, are studied, and anti-PC is determined by ELISA.

Results: Having low levels of anti-PC (below tertile or quartile) was associated with SLE, with CVD and atherosclerosis in SLE, and with being a non-responder to biologics in rheumatoid arthritis. Anti-PC promoted polarization of T cells from SLE patients into T regulatory cells, and from a lower level than among controls, T regs normalized in SLE patients after anti-PC exposure. Other potential underlying mechanisms include an anti-inflammatory property (inhibition of pro-inflammatory lipids which are raised in SLE); inhibition of uptake of oxidized LDL in macrophages; increased clearance by phagocytosis of dead cells. Anti-PC levels were very high in New Guinea among people living a traditional “stone age” life, and where rheumatic diseases and chronic inflammatory conditions are virtually unknown and also anti-PC was associated with some infectious agents there.

Conclusion: Low anti-PC could contribute to development of autoimmune and rheumatic disease, in addition to atherosclerosis and CVD. One underlying cause could be lack of exposure to some microorganisms. These findings could have therapeutic implications, including immunization to raise anti-PC levels. 

Biography:

José Moreno is an MD from the National University of Mexico, with clinical training in Rheumatology and PhD in Immunology with major focus on immunobiology of antigen processing and autoimmunity. He did two postdoctoral trainings in Dallas (Southwestern Medical College) and Heidelberg (Deutsches Krebsforschungszentrum). He has published over 50 papers in international peer-reviewed journals and his currently the Director of Research of Hospital Juárez de México. He is a Member of the National Academy of Medicine (Mexico).

Abstract:

Understanding the pathogenesis of autoimmune diseases remains one of the major challenges of modern immunology. High-throughput analysis, including the study of the association of genetic variants to disease and the global analysis of gene-expression profiles provide the basis for in depth analysis of the molecular pathogenesis of diseases. We examined global gene expression profiles by immunocompetent cells in healthy (C57BL/6-J and Balb/c-J) and lupus (MRLlpr/lpr) mice by means of Affymetrix GeneChip™ Mouse Genome 430 2.0 microarrays to identify differentially- expressed genes (DEG) and pathways in autoimmunity. Regardless of differences between BOT strains of healthy mice, pathways over-represented in lpr-mice were: positive regulation of immune response, response to interferon-β, cell killing, immune response-regulating signaling pathway, response to interferon-g (GO-biological process); plus: abnormal response to infection, abnormal immune system physiology, abnormal innate immunity, abnormal cytokine secretion, abnormal adaptive immunity (GO-phenotype), among several others. Further analysis by means of CIBERSORTTM revealed that lpr-mice over-represented genes correspond to T follicular helper (Tfh) and plasma cells. By flow cytometry, relative numbers of both CD4+ and CD8+ T cells in the spleen were decreased, whereas B220+ CD5+ cells were greatly increased. Comparing to data from NZB/NZW F1 lupus mice available in public databases, there was a similar increase in plasma cell genes, but BW mice had an increased representation of memory CD4+ cell genes instead of Tfh. Among the most relevant DEGs found in lpr-mice (all of them overexpressed) were cytokines (Il21, Il10, Il4, Ifn-g etc.), chemokines (Ccl8, Ccl2, Ccl3, Ccl4, Cxcl10, Cxcl11, etc.) and their receptors (Ccr1, Ccr2, Cxcr3), costimulatory surface molecules (Cd28, Ctla-4, Pd-1, Icos, Slamf6, Lag3, Btn1a1), signal transduction (Tnk1, Pik3ap1, Grp84, Lat), transcription (Gfi1, E2f) proteins, and many others (Brca1, Brca2). In conclusion, our results suggest, as expected, that murine lupus is a highly complex syndrome in which varying patterns of gene expression, due to different genetic backgrounds yield closely resembling clinical phenotypes of what we know as systemic lupus erythematosus.

Biography:

I, David R Thomas, am not a Doctor of medicine as some seem to suggest, but I am a self-taught Lyme disease survivor/advocate that does speak, teach, and share his views of my many experiences, that will need to be acknowledged along the way, to understanding this dreadful experience of Tick-borne disease medical challenges. It is sad that our medical community has found itself so far behind in this pandemic of So many diseases. This article pertains to my experiences through the challenges I have experienced and share with so many more I cannot count.

Abstract:

The perils of invisible disease and Lyme related issues, has brought me full circle in life. I have found that what is perceived as professional medicine has become distorted in the many minds that control medicine. This means that when a Doctor is taught one thing that his professors believe to be tried and true knowledge of a disease, the Doctor will likely not sway from those teachings. These are the controllers of medicine. The Doctors are, for the most part, not trouble-shooters and problem-solvers as they are book learners. They may want you to think they are king of the patients’ world. However, in the world of silent diseases such as tick-borne issues, they are often the patients’ dimming hope and demise. Doctors do not go to school to learn to be doctors today. It seems to me that most go for the money and they figure that all they have to do is memorize books of teachings - which are outdated. Then they deliver the outdated information to the patient. This is all smoke and mirrors. The Doctor is often left with frustration, and a big fat paycheck, that is really hindering the health of the country rather than improving the health of the country. We need to take the control of pharmacy and drug producers away from pharmacy-controlled Doctors, politicians and insurance companies. I feel all medical leaders are pharmacy bought and paid. They are in control of a profit machine that is, in truth, destroying world health programs and benefiting from the great profit machine. This is the great bottom line. This brings me to outdated medical practices. My research has found that outdated medicine has hindered the medical and patient communities concerned with Lyme and co-infections. In the ‘non-Lyme literate’ world, nine out of 10 general practitioners don't recognize our disease, but they can name the many symptoms caused by our disease. There is a pill for most symptoms related to tick-borne related health issues.

Biography:

Anna Wajda, PhD is an assistant professor at the Molecular Biology Department, National Institute of Geriatrics, Rheumatology and Rehabilitation in Warsaw, Poland. She has received her PhD in the field of medical biology from Pomeranian Medical University in Szczecin, Poland. Over the past few years, she has done research in Toxicology, Medical Technology and Clinical Pharmacology.Dr. Wajda currently focuses on genetic factors in the function of the immune system and autoimmune diseases.

Abstract:

The aim of our study was to determine the serum levels of IL-21, IL-35, TNF-α, BAFF and VEGF in patients with rheumatoid arthritis (RA), systemic lupus erythematoses (SLE), antiphospholipid syndrome (APS) and mixed connective tissue disease (MCTD), and in healthy subjects. We examined 14 RA, 20 SLE, 22 MCTD and 21 APS patients, and 22 controls by ELISA test. It was observed that BAFF serum concentration was the highest in patients with APS, but the lowest in patients with RA (p=0.02). The VEGF serum levels was the highest in RA patients than in other examined groups. Only in few patients with RA serum, TNF-α level was elevated. In general, TNF-α was not detected in serum of patients with above mentioned diseases excluding APS group (average concentration 3 pg/ml). Additionally, this cytokine was not observed in healthy subjects . We also found that patients with APS and SLE were characterized by higher IL-35 serum levels than patients with RA. Moreover, significantly higher concentration of IL-35 was observed in healthy subjects than in RA patients. APS patients were characterized by the lowest concentration of IL-21 in serum, compared to other examined groups. We also found that in patients with APS and TRU, the BAFF serum levels was higher than the TNF-α serum levels. Additionally, significant correlation between BAFF and TNF-α levels was observed (R²=0.77, p<0.0001). In patients with RA the BAFF as well as VEGF serum levels were much higher that the TNF-α and IL-35. Our study suggests that BAFF may be the most important cytokine in all rheumatic diseases.

Biography:

A Paradowska-Gorycka has completed her PhD from Centre of Biostructure Medical University of Warsaw. From 2016 she is the Head of the Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland. She has participated in numerous scientific conferences and is the author of over 50 scientific papers.

Abstract:

Because systemic lupus erythematosus (SLE) is a disease with a strong genetic component and the cytokine production was found to be under genetic control, we decided to explore whether polymorphisms located in the TGF-β and IL-6 genes may be associated with SLE. 216 SLE patients and 552 controls were examined for TGF-β rs1800469 and rs1800470 as well as IL-6 rs2069827 and rs1800795. An increased frequency of the TGF-β rs1800469 TT genotype and T allele was found in SLE patients (p=0.02). The TGF-β rs1800470 C allele was more frequent in SLE patients than in controls (45% vs. 40%). We found no association between of the IL-6 rs1800795 and rs2069827 and SLE susceptibility. The genotype-phenotype analysis showed association between the TGF-β 869 T/C and mean value of APTT and INR (p=0.01 and p=0.05, respectively); TGF β -509 C/T and mean value of CRP, ESR, hemoglobin, APTT Pt and INR (p=0.05, p=0.03, p<0.001, p=0.03, p=0.03 and p=0.05, respectively) as well as anti-SSA and anti-Sm presence (p=0.04 and p=0.03, respectively); the IL-6 -174 G/C and SLICC (p=0.05), anti-SSA (p=0.05) and anti-SSB (p=0.05). A higher TGF-β and IL-6 serum level was found in SLE patients compared to controls (both p<0.0001). In SLE patients with the TGF-β-509 TT genotype the TGF-β serum levels were higher than in SLE patients with TGF-β-509 CC and TGF-β -509 CT genotypes. Our results suggested that the TGF β -509 C/T variant may be considered as a genetic marker for SLE in the Polish population.

Biography:

Anna Wajda, PhD is an assistant professor at the Molecular Biology Department, National Institute of Geriatrics, Rheumatology and Rehabilitation in Warsaw, Poland. She has received her PhD in the field of medical biology from Pomeranian Medical University in Szczecin, Poland. Over the past few years, she has done research in Toxicology, Medical Technology and Clinical Pharmacology.Dr. Wajda currently focuses on genetic factors in the function of the immune system and autoimmune diseases.

Abstract:

In systemic lupus erythematosus (SLE), the immune responses, immune homeostasis and self-tolerance is actively regulated by several types of cells as well as cytokines. The aim of our study was to explore whether IL-1, IL-10 and TNFα genetic variants may be associated with SLE. We examined 216 patients with SLE and 552 unrelated healthy controls. The polymorphisms were evaluated by RT-PCR. The IL-1β rs16944 T allele as well as rs1143634 T allele were significantly frequent in SLE patients than controls (p=0.003 and p=0.017, respectively). The IL-10 rs180872 A allele was more frequent in SLE patients (p=0.003), furthermore, the IL-10 rs1800896 G allele was more frequent in controls (p=0.03). The TNF-α rs1800629 A allele was more frequent in SLE patients than in controls (p=0.002). No association was found between of the TNF-α rs361525 and rs1800610 and SLE susceptibility. The genotype-phenotype analysis showed association between the IL-1β rs1143634 and mean value of C3 (p=0.006); the IL-10 rs180872 and AST (p=0.07); the IL-10 rs1800896 and mean value of C4 (p=0.04); TNF-α rs361525 and SLICC (p=0.02); the TNF-α rs1800610 and Pt (p=0.003) and INR (p=0.004). Our study demonstrated that IL-1β and IL-10 genetic variants are associated with SLE susceptibility in Polish population.

Biography:

A Paradowska-Gorycka has completed her PhD from Centre of Biostructure Medical University of Warsaw. From 2016 she is the Head of the Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland. She has participated in numerous scientific conferences and is the author of over 50 scientific papers.

Abstract:

In the present study, we tested that genetic variation in the APOH as well as TF genes may be associated with systemic lupus erythematosus (SLE) risk and clinical phenotypes in Polish patients. We used a case-control study and examined 216 patients with SLE and 552 healthy subjects for four TF gene SNPs (rs958587, rs3811647, rs3917615, rs1361600) and for three APOH gene SNPs (rs4581, rs8178835, rs8178819). We observed that APOH rs4581 C allele as well as rs8178819 T allele were more frequent in controls than in SLE patients (p=0.05 and p<0.001, respectively). Furthermore, the TF rs3811647 G allele showed tendency to frequent occurrence in healthy subjects than in SLE patients (p=0.06). In contrast, we found no evidence that TF gene SNPs rs958587, rs3917615 and rs1361600 as well as APOH SNP rs8178835 modulate the risk of SLE developing. The genotype-phenotype analysis showed significant association between the: 1) TF rs958587 and disease duration (p-=0.001), 2) TF rs3917615 and disease duration (p=0.004), 3) TF rs1361600 and disease duration (p=0.02) and mean value of ESR (p=0.01), 4) APOH rs8178819 and mean value of ESR (p=0.03) and mean value of hemoglobin (p=0.007). Present findings indicated that APOH rs4581 and rs8178819 T as well as TF rs3811647 polymorphisms may be protective against SLE in the Polish population.