scholarly journals TNFAIP3 Gene Polymorphisms in Three Common Autoimmune Diseases: Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Primary Sjogren Syndrome—Association with Disease Susceptibility and Clinical Phenotypes in Italian Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
C. Ciccacci ◽  
A. Latini ◽  
C. Perricone ◽  
P. Conigliaro ◽  
S. Colafrancesco ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Variant Allele ◽  
Italian Population ◽  
Systemic Lupus ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Necrosis Factor Alpha

Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-κB, a transcription factor that regulates expression of various proinflammatory genes. Variants in TNFAIP3 gene have been described as associated with susceptibility to several AIDs. Here, we analyzed two TNFAIP3 polymorphisms in Italian patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren’s syndrome (pSS), to verify if the genetic variability of TNFAIP3 gene is involved in genetic predisposition to AIDs also in the Italian population. We recruited 313 SLE patients, 256 RA patients, 195 pSS patients, and 236 healthy controls. Genotyping of rs2230926 and rs6920220 in TNFAIP3 gene was performed by an allelic discrimination assay. We carried out a case/control association study and a genotype/phenotype correlation analysis. A higher risk to develop SLE was observed for rs2230926 (P=0.02, OR=1.92). No association was observed between this SNP and the susceptibility to pSS or RA. However, the rs2230926 variant allele seems to confer a higher risk to develop lymphoma in pSS patients, while in RA patients, the presence of RF resulted significantly associated with the variant allele. Regarding the rs6920220 SNP, we observed a significant association of the variant allele with SLE (P=0.03, OR=1.53), pSS (P=0.016, OR=1.69), and RA (P=0.0001, OR=2.35) susceptibility. Furthermore, SLE patients carrying the variant allele showed a higher risk to develop pericarditis, pleurisy, and kidney complications. Our results support the importance of the TNFAIP3 gene variant role in the development of different autoimmune diseases in the Italian population and furtherly confirm a sharing of genetic predisposing factors among these three pathologies.

scholarly journals AB0002 ASSOCIATION OF C1Q GENETIC POLYMORPHISMS WITH SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS IN BULGARIAN COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1036.3-1036
Author(s):  
M. Kosturkova ◽  
G. Mihaylova ◽  
M. Radanova
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Gene Cluster ◽  
Lupus Erythematosus ◽  
Annual Review ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Allelic Discrimination Assay ◽  
Increased Risk

Background:Complement is strongly implicated in the pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Its component C1q plays a dualistic role, triggering the inflammatory cascade on one hand and directing the clearance of immune complexes on the other. Homozygous genetic deficiency of C1q is strongly associated with SLE and SLE-like phenotype as almost 90% of C1q deficient individuals develop SLE or similar disease. Nevertheless, there are few and inconsistent studies exploring the single nucleotide polymorphisms (SNPs) of the C1q gene cluster in relation to the pathogenesis of SLE and RA.Objectives:The aim of the study was to evaluate the possible association of five SNPs – rs292001, rs172378, rs294179, rs665691 and rs682658 in complement C1q gene cluster with susceptibility to SLE and RA in Bulgarian cohort.Methods:Fifty patients with SLE, sixty-one patients with RA and sixty-seven healthy controls were genotyped for the five SNPs by TaqMan allelic discrimination assay.Results:Frequency of genotypes and alleles of rs294179, rs665691 and rs682658 SNPs was similar between patients with SLE, RA and healthy controls. For rs172378 SNP, the minor G allele (OR = 2.73; 95% CI, 1.59-4.67, p=0.0003) and GG genotype (OR = 5.12; 95% CI, 1.60-16.49, p=0.006) were associated with susceptibility to RA. In our cohort in accordance with others, AA rs292001 SNP genotype was associated with increased risk for RA (OR = 3.32; 95% CI, 1.19-9.20, p=0.021). For SLE patients, AA rs292001 SNP genotype was low presented and did not associate with disease.Conclusion:GG genotype of rs172378 SNP in C1q gene cluster could be considered as a new risk factor for RA.References:[1]Diane Scott et al (2016). The paradoxical roles of C1q and C3 in autoimmunity. Immunobiology, 719-25. doi:10.1016/j.imbio.2015.05.001.[2]Giles JL et al (2015). Functional analysis of a complement polymorphism (rs17611) associated with rheumatoid arthritis. J Immunol., 3029-34. doi:10.4049/jimmunol.1402956.[3]Holers, V. M. (2018). Complement in the Initiation and Evolution of Rheumatoid Arthritis. Frontiers in immunology, 1057. doi:10.3389/fimmu.2018.01057.[4]Lintner, K. E. (2016). Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases. Frontiers in immunology, 36. doi:10.3389/fimmu.2016.00036.[5]Lu, J. &. (2017). C1 Complex: An Adaptable Proteolytic Module for Complement and Non-Complement Functions. Frontiers in immunology, 592. doi:10.3389/fimmu.2017.00592.[6]Manderson, A. P. (2004). The role of complement in the development of systemic lupus erythematosus. Annual review of immunology, 431-456. doi:10.1146/annurev.immunol.22.012703.104549.[7]Martens, H. A. (2009). Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity. Annals of the rheumatic diseases, 715–720. doi:10.1136/ard.2007.085688.[8]Namjou B, G.-M. C. (2009). Evaluation of C1q genomic region in minority racial groups of lupus. Genes Immun., 517-24. doi:10.1038/gene.2009.33.[9]Radanova M et al(2015). Association of rs172378 C1q gene cluster polymorphism with lupus nephritis in Bulgarian patients. Lupus, 280-9. doi:10.1177/0961203314555173.[10]Rafiq S et al (2010). Assessing association of common variation in the C1Q gene cluster with systemic lupus erythematosus. Clin Exp Immunol., 284-9. doi:10.1111/j.1365-2249.2010.04185.x.[11]Schejbel L et al (2011). Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations. Genes Immun., 626-634.[12]Trouw LA et al (2013). Genetic variants in the region of the C1q genes are associated with rheumatoid arthritis. Clin Exp Immunol., 76-83. doi:10.1111/cei.12097.[13]Trouw L. A. (2017). The complement system as a potential therapeutic target in rheumatic disease. Nature reviews. Rheumatology, 538–547. doi:10.1038/nrrheum.2017.125.[14]Walport M. J. (2002). Complement and systemic lupus erythematosus. Arthritis research, S279–S293. doi:10.1186/ar586.Disclosure of Interests:None declared

scholarly journals Increased Frequency of the Uncommon Allele of a Tumour Necrosis Factor Alpha Gene Polymorphism in Rheumatoid Arthritis and Systemic Lupus Erythematosus

1994 ◽  
Vol 12 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Victor A. Danis ◽  
Michelle Millington ◽  
Valentine Hyland ◽  
Ron Lawford ◽  
Qirong Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Tumour Necrosis Factor ◽  
Lupus Erythematosus ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Alpha ◽  
Systemic Lupus ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

The frequency of the uncommon allele (TNF2) of a polymorphism in the promoter region of the tumour necrosis factor alpha (TN Fα) gene in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was found to be 3 times that of the normal anglo-saxon population. In SLE patients, this allele was strongly associated with HLA-DR3 expression and was also more frequent in patients who did not have malar rash. Functional studies of normal monocyte cytokine production in vitro showed that this genotype was associated with increased IL-1α protein production but there were no differences in the production of TNFα protein.

A comparative study on clinical and serological characteristics between patients with rhupus and those with systemic lupus erythematosus and rheumatoid arthritis

Lupus ◽  
2020 ◽  
Vol 29 (10) ◽  
pp. 1216-1226
Author(s):  
Beatriz Frade-Sosa ◽  
Javier Narváez ◽  
Tarek Carlos Salman-Monte ◽  
Raul Castellanos-Moreira ◽  
Vera Ortiz-Santamaria ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Disease Duration ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Classification Criteria ◽  
Systemic Lupus ◽  
Cross Sectional

Background The concomitant presence of two autoimmune diseases – systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) – in the same patient is known as rhupus. We evaluated a group of patients with rhupus to clarify further their clinical, serological and immunogenic features in a multi-centre cohort. In addition, the study aimed to explore the utility of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in our group of patients with rhupus. Methods This was a cross-sectional study. We included rhupus patients from 11 different rheumatology departments, and compared them to SLE and RA patients at a ratio of 2:1. All information was recorded following a pre-established protocol. Results A total of 200 patients were included: 40 rhupus patients and 80 each of SLE and RA patients as controls. Disease duration was similar among SLE and rhupus groups (around 13 years), but the RA group had a significantly lower disease duration. Main clinical manifestations were articular (94.2%), cutaneous (77.5%) and haematological (72.5%). Rhupus patients had articular manifestations similar to those expected in RA. Only 10% of rhupus patients had renal involvement compared with 25% of those with SLE ( p < 0.05), while interstitial lung disease was more common in patients affected by RA. The 2019 EULAR/ACR SLE criteria were met in 92.5% of the rhupus patients and in 96.3% of the SLE cohort ( p > 0.05). Excluding the joint domain, there were no differences between the numbers of patients who met the classification criteria. Conclusion Rhupus patients follow a particular clinical course, with full expression of both SLE and RA in terms of organ involvement, except for a lower prevalence of kidney affection. The new 2019 EULAR/ACR SLE criteria are not useful for differentiating SLE and rhupus patients. A new way of classifying autoimmune diseases is needed to identify overlapping clusters.

scholarly journals Pharmacovigilance of Biopharmaceuticals in Rheumatic Diseases, Adverse Events, Evolution, and Perspective: An Overview

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 303
Author(s):  
Sandra Rodríguez ◽  
Andrés Muñoz ◽  
Rosa-Helena Bustos ◽  
Diego Jaimes
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Adverse Events ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Cell Mediated Immunity ◽  
Systemic Lupus ◽  
Biological Drugs ◽  
Necrosis Factor Alpha ◽  
Post Marketing

Since we have gained an understanding of the immunological pathophysiology of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, treatment based on biological drugs has become a fundamental axis. These therapies are oriented towards the regulation of cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1, and the modulation of cell-mediated immunity (B cells and T cells) by anti CD20 or anti CTAL-4 agents, and can increase the risk of associated infections or adverse events (AE). In this context, the entry of biotherapeutics represented a challenge for pharmacovigilance, risk management and approval by the main global regulatory agencies regarding biosimilars, where efficacy and safety are based on comparability exercises without being an exact copy in terms of molecular structure. The objective of this review is divided into three fundamental aspects: (i) to illustrate the evolution and focus of pharmacovigilance at the biopharmaceutical level, (ii) to describe the different approved recommendations of biopharmaceuticals (biological and biosimilars) and their use in rheumatic diseases (RDs) such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE) and other less frequent RD like cryopyrin-associated autoinflammatory syndromes (CAPS), and (iii) to identify the main AE reported in the post-marketing phase of RD biopharmaceuticals.

scholarly journals Spondyloarthropathies in Autoimmune Diseases and Vice Versa

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Oscar M. Pérez-Fernández ◽  
Rubén D. Mantilla ◽  
Paola Cruz-Tapias ◽  
Alberto Rodriguez-Rodriguez ◽  
Adriana Rojas-Villarraga ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Clinical Characteristics ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Systemic Lupus ◽  
Two Phase ◽  
Cross Sectional

Polyautoimmunity is one of the major clinical characteristics of autoimmune diseases (ADs). The aim of this study was to investigate the prevalence of ADs in spondyloarthropathies (SpAs) and vice versa. This was a two-phase cross-sectional study. First, we examined the presence of ADs in a cohort of patients with SpAs (N=148). Second, we searched for the presence of SpAs in a well-defined group of patients with ADs (N=1077) including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SS). Among patients with SpAs, ankylosing spondylitis was observed in the majority of them (55.6%). There were two patients presenting with SS in the SpA group (1.4%) and 5 patients with autoimmune thyroiditis (3.5%). The global prevalence of ADs in SpAs was 4.86%. In the ADs group, there were 5 patients with SpAs (0.46%). Our results suggest a lack of association between SpAs and ADs. Accordingly, SpAs might correspond more to autoinflammatory diseases rather than to ADs.

scholarly journals Helicobacter pylori and its association with autoimmune diseases: Systemic lupus erythematosus, rheumatoid arthritis and Sjögren syndrome

2021 ◽  
pp. 100135
Author(s):  
Ivet Etchegaray-Morales ◽  
Erick Alejandro Jiménez-Herrera ◽  
Claudia Mendoza-Pinto ◽  
Adriana Rojas-Villarraga ◽  
Salvador Macías-Díaz ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Helicobacter Pylori ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Systemic Lupus

Treatment of Severe Autoimmune Diseases with Autologous Hematopoietic Stem Cell Transplantation

2017 ◽  
Vol 71 (1) ◽  
pp. 10-14
Author(s):  
Zlate Stojanoski ◽  
Anzelika Karadzova-Stojanoska ◽  
Aleksandra Pivkova-Veljanovska ◽  
Sonja Genadieva-Stavrik ◽  
Lazar Cadievski ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Autoimmune Disease ◽  
Stem Cell Transplantation ◽  
Autoimmune Diseases ◽  
Cell Transplantation ◽  
Lupus Erythematosus ◽  
Systemic Lupus

Abstract Introduction. Autoimmune diseases are a family of more than 100 heterogeneous conditions that affect 5 to 8% of the world’s population. The etiology is still un-known but the disregulation of the regulatory T-lymphocytes play a central role inthe autoimmunity and the success of the long-term remission. Although conventional immunosuppression and new biological agents can provide disease control in severely affected patients, such treatments are rarely curative and alternative strategies are needed. Indeed, severe forms of systemic autoimmune diseases, such as multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), hematologic immune cytopenia (HIC) and Crohn’s disease are difficult to be treated. High-dose immunosuppressive therapy followed by autologous stem cells transplantation is reliable option for a successive treatment of this group of patients. Aim. To determine the safety of the procedure of autologous stem cell transplantation in patients with autoimmune diseases and concomitant malignant hematological disorders. Methods. During a period of 15 years (from September 2000 to September 2015) at the University Clinic of Hematology in Skopje we have treated 6 patients with autoimmune disease and concomitant hematological neoplasm. None of the patients was treated for primary autoimmune diseases. Two men and 4 women, with median age of 47 years were treated. Sjogren syndrome and multiple myeloma were found in 2 patients, polyartheritis nodosa and multiple myeloma in 1 patient, rheumatoid arthritis and acute myeloblastic leukemia in 1, systemic lupus erythematosus and non-Hodgkin lymphoma in 1; severe psoriasis and acute myeloblastic leukemia in 1 patient. Results. All treated patients are alive after trans-planted procedure, with transplant related mortality day +100: 0. Conclusion. Autologous stem cell transplantation is safe and recommended option for treatment ofpatients with autoimmune disease and hematologic neoplasm.

scholarly journals Endothelial Alterations in Systemic Lupus Erythematosus and Rheumatoid Arthritis: Potential Effect of Monocyte Interaction

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Laura Atehortúa ◽  
Mauricio Rojas ◽  
Gloria M. Vásquez ◽  
Diana Castaño
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Systemic Lupus ◽  
Endothelial Cell Activation ◽  
Proinflammatory Mediators

Patients with systemic autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are prone to develop atherosclerosis and cardiovascular diseases five times more often than the general population; this increase in frequency could be partially explained by an increase in the macrovasculature endothelial damage. In these autoimmune diseases, a microvascular endothelial injury has also been reported in different organs and tissues, especially in sites where ultrafiltration processes occur. Different components that are characteristic to the immunopathology of RA and SLE could be involved in the endothelial cell activation, permeability increase, functional alteration, and vascular injury. Circulating immune complexes (IC) detected in SLE and RA have been proposed to participate in the endothelial injury. In the vascular environment, IC can generate different responses that could be mediated by monocytes, because these cells have patrolling and monitoring functions on the endothelium. However, with certain stimuli such as TLR ligands, the monocytes are retained in the lumen, releasing proinflammatory mediators that participate in the endothelial damage. This paper aims to review some aspects about the endothelial activation and dysfunction in the context of SLE and RA, as well as the potential role that monocytes apparently play in this process.

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