Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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29097951 | Effect of Foot Manipulation on Pregnancy-Related Pelvic Girdle Pain: A Feasibility Study. | 2017 Sep | OBJECTIVE: The objective of this study was to investigate if the research process to evaluate the effect of foot manipulation on pregnancy-related pelvic girdle pain (PPGP) is feasible. METHODS: A randomized, single-blind (patients and evaluators) pilot trial was performed to compare foot manipulation to a comparative group at 6-weekly treatment sessions at 5 physiotherapy outpatient clinics in Skaraborg primary care (Skövde, Sweden). Women at 12 to 31 weeks of pregnancy with well-defined PPGP (n = 97) and joint dysfunction or decreased range of movement in the feet were included. Women with a twin pregnancy, low back pain, rheumatoid arthritis, or other serious diseases and those who had previous foot manipulation were excluded. Visual analog scale scores were recorded before study start, before and after each treatment session, and 3 months after delivery. RESULTS: One-hundred and two women were eligible, and 97 were included (group 1: foot manipulation, n = 47; group 2: comparative treatment, n = 50); 40 and 36 in the foot manipulation and comparative treatment groups, respectively, completed the study. The foot manipulation group had a nonsignificant pain relief score compared with that of the comparative group, which had higher pain relief scores. The difference was most pronounced at the first and second treatment sessions. A power analysis showed that at least 250 individuals would be needed in each group to confirm the effect of foot manipulation. CONCLUSIONS: This study showed that it is feasible to assess the effect of foot manipulation on PPGP in a multicenter physical therapy outpatient clinic setting. A new larger study should choose a different comparative method and test this hypothesis in a full-scale trial. | |
28967793 | Fostamatinib for persistent/chronic adult immune thrombocytopenia. | 2018 Jan | Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by phagocytosis and destruction of autoantibody-coated platelets via spleen tyrosine kinase (Syk)-mediated signal transduction in macrophages. Effectiveness of existing therapies varies, and even leading treatments (e.g., IVIg, splenectomy, rituximab, thrombopoietic agents) do not provide optimal management for a substantial number of patients with chronic ITP. Fostamatinib disodium is an orally-bioavailable investigational agent being developed for treatment of primary persistent/chronic adult ITP. Fostamatinib inhibits FcR-triggered, Syk-dependent cytoskeletal rearrangement during phagocytosis. Promising findings have been described in several autoimmune diseases, including rheumatoid arthritis, and sustained responses with manageable adverse events observed with ongoing treatment in patients with heavily treated chronic ITP. Fostamatinib represents an active therapy targeting a previously unexplored mechanism of ITP pathogenesis. | |
28953168 | Bipedicle Flaps for Posterior Elbow Reconstruction. | 2017 Dec | Chronic posterior elbow soft tissue defects often require soft tissue reconstruction because of exposure of the underlying triceps tendon and proximal ulna. Current options for soft tissue coverage require sacrifice of a local muscle or microsurgery. The purpose of this study is to evaluate patient and surgical outcomes after reconstruction of small-sized to medium-sized (<50 cm) posterior elbow defects with bipedicle advancement flaps. A retrospective chart review was performed for 3 patients who underwent posterior elbow reconstruction with bipedicle flaps. The etiology of the soft tissue elbow defect was chronic infected olecranon bursitis (n=2) and exposed olecranon plate after open fracture (n=1). Patient comorbidities included: diabetes, CREST (Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia) syndrome, and rheumatoid arthritis. The mean patient age at time of reconstruction was 44 years (39 to 51 y), and the mean area of soft tissue defect was 39.3 cm (24 to 54 cm) after debridement of involved tissue. All patients had positive intraoperative cultures and were treated with culture-directed long-term intravenous antibiotics. There were no surgical complications or flap loss. All patients had reepithelialization of the donor site by postoperative week 8 and stable soft tissue coverage of the elbow after surgery at final follow-up with full preoperative elbow range of motion. This technique offers a simple, reliable solution for soft tissue coverage of the posterior elbow using excess local tissue for primary closure of posterior elbow wounds with minimal donor-site morbidity. | |
28692448 | The use of biosimilars in paediatric inflammatory bowel disease. | 2017 Oct | PURPOSE OF REVIEW: After expiry of the patent of originator anti-tumor necrosis factor drug infliximab (Remicade), CT-P13 was in 2013 the first infliximab biosimilar to be approved by the European Medicine Agency (EMA) for the same indications as the reference drug, including paediatric inflammatory bowel disease (IBD). The approval was based on extrapolation, after extensive in-vitro studies and clinical experience in patients with ankylosing spondylitis and rheumatoid arthritis. The extrapolation of CT-P13 to IBD and to paediatric patients raised concerns among paediatric IBD specialists. RECENT FINDINGS: Now, almost 4 years later, we can conclude that those concerns have been resolved. There are a growing number of postmarketing studies and real-life data, so far mostly in adults and some in children with IBD. These studies show reassuring comparable efficacy, safety and immunogenicity between CT-P13 and the reference Infliximab. CONCLUSION: In Europe, biosimilars are increasingly regularly prescribed drugs in paediatric IBD. Due to their lower cost, treatment expenses have gone down considerably (up to 30% or more in some countries) and patient access has improved. However, additional well designed studies to investigate long term follow-up of biosimilars in children are still needed. In addition, clinical studies addressing pharmacokinetics, pharmacodynamics and optimal use of infliximab (originator as well as biosimilar) are still desirable. | |
28673589 | Hepatitis B vaccine non response: A predictor of latent autoimmunity? | 2017 Jul | Unresponsiveness to Hepatitis B virus (HBV) vaccine has been associated with interleukins involved with Th1 functioning including Interleukin-8 (IL-18) and Interferon-γ (IFN-γ). IL-18 and IFN-γ have also been implicated in the onset of different types of immune-mediate inflammatory conditions such as Type 1 Diabetes (T1D), Celiac disease (CD), rheumatoid arthritis (RA), obesity and systemic lupus erythematosus (SLE). Taking into account that HBV vaccination is provided in the 1st year of life worldwide, I propose that all babies should be tested for anti-HBs response after completion of the vaccine series. And I suggest that children with undetectable anti-HBs titers after recommended immunization schedule as well as the additional booster doses should be followed up over time because they may be at risk of developing a number of autoimmune disorders. In this light, the non-responsiveness to HBV vaccine might be a predictor of latent autoimmunity. For that reason, research studies are needed in order to verify the existence of potential IL-18 and IFN-γ gene polymorphisms to utilize as biomarkers of latent autoimmunity. As a final point, administration of neutralizing antibodies against IFN-γ and/or IL-18 might represent a future target for immune-modulatory therapeutic approach to halt or even reverse autoimmune phenomena. | |
28556916 | Intestinal dysbiosis and probiotic applications in autoimmune diseases. | 2017 Sep | In humans, a complex interaction between the host immune system and commensal microbiota is required to maintain gut homeostasis. In this symbiotic relationship, the microbiota provides carbohydrate fermentation and digestion, vitamin synthesis and gut-associated lymphoid tissue development, as well as preventing colonization by pathobionts, whereas the host offers a niche and nutrients for the survival of the microbiota. However, when this mutualistic relationship is compromised and an altered interaction between immune cells and microorganisms occurs, the gut microbiota may cause or contribute to the establishment of infectious diseases and trigger autoimmune diseases. Researchers have made efforts to clarify the role of the microbiota in autoimmune disease development and find new therapeutic approaches to treat immune-mediated diseases. However, the exact mechanisms involved in the dysbiosis and breakdown of the gut epithelial barrier are currently unknown. Here, we provide a general overview of studies describing gut microbiota perturbations in animal models of autoimmune diseases, such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. Moreover, we include the main studies concerning dysbiosis in humans and a critical discussion of the existing data on the use of probiotics in these autoimmune diseases. | |
28502966 | Laparoscopic Repair of Vaginal Evisceration after Abdominal Hysterectomy for Uterine Corpu | 2017 | Vaginal cuff dehiscence is a rare but serious complication that can develop after hysterectomy. Emergent surgical intervention is required for vaginal cuff dehiscence due to the potential subsequent vaginal evisceration, which may lead to necrosis of the small bowel. A 62-year-old nulliparous woman with a 30-year history of smoking, diabetes mellitus, and rheumatoid arthritis (treated with oral steroids) presented with a vaginal cuff dehiscence. Thirty-eight days before the admission, she had undergone a radical operation including total abdominal hysterectomy for uterine corpus cancer at another hospital. We performed emergent laparoscopic surgery to reduce the prolapsed small bowel into the abdominal cavity and repaired the vaginal cuff with a two-layer continuous closure using absorbable barbed sutures. The patient experienced no postoperative complications, and no recurrence of the vaginal cuff dehiscence occurred. Vaginal cuff dehiscence and evisceration can be surgically managed using an abdominal, vaginal, or laparoscopic approach, and the choice of method should be based on patient characteristics and the surgeon's skills. Laparoscopic vaginal cuff repair with a two-layer continuous closure using absorbable barbed sutures is a minimally invasive technique that is safe and effective for medically stable patients with no small bowel injury or vascular compromise and no pelvic abscess. | |
28475463 | Immune Diseases Associated with TREX1 and STING Dysfunction. | 2017 May | The innate immune system is the first line of defense against invading pathogens. One important feature of innate immune recognition is self versus nonself discrimination. The selectivity for microbial ligands is achieved through substrate motif specificity, spatial compartmentalization, and functions of negative regulators. Loss-of-function mutations in negative regulators or gain-of-function mutations in drivers of innate immune signaling have been associated with autoimmune diseases such as lupus, rheumatoid arthritis, inflammatory vasculopathy, and a variety of interferonopathies. This review will focus on TREX1 and STING, which are opposing regulators of the cytosolic DNA-sensing pathway. Tremendous effort over the past decade among academic and clinical research groups has elucidated molecular mechanisms underlying immune diseases associated with TREX1 and STING dysfunction. We have also witnessed rapid therapeutic translation of the molecular findings. Several targeted treatment options or druggable candidates are now available for these once incurable diseases. With great enthusiasm from both academia and industry partners, we look forward to seeing the remaining scientific questions answered and, more importantly, the affected patients benefited from these discoveries. | |
28469051 | Statins for prevention of cardiovascular disease in systemic lupus erythematosus. | 2017 Apr | OBJECTIVE: In systemic lupus erythematosus (SLE), cardiovascular disease (CVD) is an important cause of long-term morbidity, which could be affected by statin use. Here we review the evidence for the use of statins for the prevention of CVD in patients with SLE. METHODS: The PubMed database was searched using a query combining SLE and statins. RESULTS: The search yielded nine relevant clinical studies. Seven studies reported on radiological findings that correlate with atherosclerosis and mainly revealed that statin treatment resulted in a slight decrease in progression of carotid intima-media thickness and an increase in flow-mediated vasodilatation. Two studies investigated CVD and mortality. In a group of SLE patients that had received a kidney transplantation, three of 23 statin-treated SLE patients experienced cardiac events compared with four of ten placebo- reated controls. Moreover, in a retrospectively studied cohort of SLE patients with dyslipidaemia, statin treatment in 777 patients was associated with a large decrease in coronary heart disease (hazard ratio [HR] = 0.20), cerebrovascular disease (HR = 0.14), end-stage renal disease (HR = 0.22) and mortality (HR = 0.44) compared with 1317 patients that had not been prescribed statins. However, the latter retrospective study was subject to bias and causality can only be proven in a randomised trial. Statins showed a good safety profile in SLE patients. CONCLUSION: Whilst awaiting new prospective randomised studies, we recommend prescription of statins in SLE patients with increased cardiovascular risk according to the current recommendations for cardiovascular risk management in rheumatoid arthritis. | |
28452955 | Peripheral Nerve Fibers and Their Neurotransmitters in Osteoarthritis Pathology. | 2017 Apr 28 | The importance of the nociceptive nervous system for maintaining tissue homeostasis has been known for some time, and it has also been suggested that organogenesis and tissue repair are under neuronal control. Changes in peripheral joint innervation are supposed to be partly responsible for degenerative alterations in joint tissues which contribute to development of osteoarthritis. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters, allowing response to peripheral neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells and chondrocytes of different origin, which express distinct subtypes of adrenoceptors (AR), receptors for vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). Some of these cell types synthesize and secrete neuropeptides such as SP, and they are positive for tyrosine-hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters are involved in the pathology of inflammatory diseases such as rheumatoid arthritis (RA) which manifests mainly in the joints. In addition, they seem to play a role in pathogenesis of priori degenerative joint disorders such as osteoarthritis (OA). Altogether it is evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for joint tissue and bone homeostasis. They modulate articular cartilage, subchondral bone and synovial tissue properties in physiological and pathophysiological conditions, in addition to their classical neurological features. | |
28233089 | The microbiome and systemic lupus erythematosus. | 2017 Apr | The microbiota, which is comprised of the collective of all microbes inhabiting the gut and its effect on the human host in which it resides, has become a growing field of interest. Various parameters of health and disease have been found to be associated with the variation in the human gut microbiome. In recent years, many studies have demonstrated an important role of gut microbes in the development of various illnesses including autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. Although the mechanism of the disease involves both genetic and environmental factors, lupus has been found to be affected by the composition of the microbes lining the intestines. Several recent studies have suggested that alterations of the gut microbial composition may be correlated with SLE disease manifestations, while the exact roles of either symbiotic or pathogenic microbes in this disease have yet to be explored. Elucidation of the roles of gut microbes in SLE will shed light on how this autoimmune disorder develops and provide opportunities for improved biomarkers of the disease and the potential to probe new therapies. This new knowledge, along with that enabling alteration in composition of the gut microbiome, via diet modification, antibiotic, and probiotics, may bring forward a new era in the future of lupus treatment. | |
28104368 | Interaction of capsaicin with calf thymus DNA: A multi-spectroscopic and molecular modelli | 2017 Apr | Studying the mode of interaction between small molecules and DNA has received much attention in recent years, as many drugs have been reported to directly interact with DNA thereby regulating the expression of many genes. Capsaicin is a capsaiciniods family phytocompound having many therapeutic applications including diabetic neuropathy, rheumatoid arthritis, prevention of DNA strand breaks and chromosomal aberrations. In this study, we have investigated the interaction of capsaicin with calf thymus DNA using a number of biophysical techniques to get an insight and better understanding of the interaction mechanism. Analysis of UV-vis absorbance spectra and fluorescence spectra indicates the formation of complex between capsaicin and Ct-DNA. Thermodynamic parameters ΔG, ΔH, and ΔS measurements were taken at different temperatures indicated that hydrogen bonding and van der Waal's forces played major role in the binding process. Additional experiments such as iodide quenching, CD spectroscopy suggested that capsaicin possibly binds to the minor groove of the Ct-DNA. These observations were further confirmed by DNA melting studies, viscosity measurements. Molecular docking provided detailed computational interaction of capsaicin with Ct-DNA which proved that capsaicin binds to Ct-DNA at minor groove. Computational molecular docking also revealed the exact sites and groups to which capsaicin interacted. | |
28083646 | Potential importance of B cells in aging and aging-associated neurodegenerative diseases. | 2017 Apr | Our understanding of B cells as merely antibody producers is slowly changing. Alone or in concert with antibody, they control outcomes of seemingly different diseases such as cancer, rheumatoid arthritis, diabetes, and multiple sclerosis. While their role in activation of effector immune cells is beneficial in cancer but bad in autoimmune diseases, their immunosuppressive and regulatory subsets (Bregs) inhibit autoimmune and anticancer responses. These pathogenic and suppressive functions are not static and appear to be regulated by the nature and strength of inflammation. Although aging increases inflammation and changes the composition and function of B cells, surprisingly, little is known whether the change affects aging-associated neurodegenerative disease, such as Alzheimer's disease (AD). Here, by analyzing B cells in cancer and autoimmune and neuroinflammatory diseases, we elucidate their potential importance in AD and other aging-associated neuroinflammatory diseases. | |
27721149 | Dihydroorotate dehydrogenase: A drug target for the development of antimalarials. | 2017 Jan 5 | Malaria is a critical human disease with extensive exploration yet unestablished due to occurrence of frequent drug resistance. This aspect of malaria pharmacology calls for the introduction of new antimalarial. The drugs reported till date targeted different stages of the parasites in order to stop their growth and proliferation. Beside this, various drugs that could inhibit the imperative enzymes of the parasite have also been reported. Amid them, dihydroorotate dehydrogenase (DHODH) has a key worth. DHODH is involved in the de novo pyrimidine biosynthesis of the malarial parasite which acts as a primary source of energy for its survival. Since life of the parasite utterly depends on pyrimidine biosynthesis, so it can be used as an apt drug target for malaria eradication. In addition to this, DHODH is also present in human and their active sites have significant structural dissimilarities, so the development of selective inhibitors may prove to be a milestone in search of new antimalarials. Inhibitors of human DHODH have been used to treat autoimmune diseases such as, rheumatoid arthritis or multiple sclerosis and have been investigated in the treatment of cancer, viral diseases, as well as in plant pathology. Here, we have reviewed the important role of DHODH as a viable drug target against malaria, its importance for the survival of the parasite, and DHODH inhibitors reported so far. The rate of success of the reported DHODH inhibitors and further required improvements have also been accounted. | |
27529600 | Repair of Acute Patellar Tendon Rupture Augmented with Strong Sutures. | 2017 May | Rupture of the patellar tendon is an uncommon injury that requires acute surgical repair to restore the function of the knee. Multiple techniques for repair have been described in the literature. Complications with these repair techniques include rerupture and extensor lag caused by gap formation at the site of repair. Thus, many surgeons have suggested augmenting the standard repair. Several methods of augmentation have been described each with disadvantages. The purpose of this article was to present our case series of six patients with acute patella tendon ruptures treated by a novel procedure using strong sutures. In this method, eight strands of four-strong sutures run within the tendon. At the patellar site, a combination of suture button and figure eight pattern techniques is used, avoiding stress concentration. The optimal tension is applied to each suture, so as the patella might be positioned at the original placement. Then all sutures are secured onto the tibia. Postoperatively with a mean follow-up of 32.7 months (range: 25-48 months), all patients had a stable knee with mean flexion of 143.3 degrees (range: 140-150 degrees) and without any extension lag. With an improvement in the International Knee Documentation Committee score to 86.8 (range: 80-92), the excellent outcome was noted in all patients. The average postoperative Lysholm score was 98.8 (range: 97-100) and the average Kujala score was 95.2 (range: 92-97). All patients recovered to near-normal strength and stability of the patellar tendon as well as restoration of function after the operation. This augmentation technique offers a distinct advantage over previous augmentation methods and materials, and may be especially useful in managing patellar tendon rupture caused by rheumatoid arthritis or other systemic conditions. For these reasons, we recommend this procedure for acute patellar tendon ruptures. | |
29083361 | Chondral tissue engineering of the reumatoid knee with collagen matrix autologous chondroc | 2017 Oct 18 | Articular cartilage repair is still a challenge. To date evidence is insufficient to support a treatment over the others. Inflammatory conditions in the joint hamper the application of tissue engineering during chronic joint diseases. Most of the Matrix Autologous Chondrocyte Implantation (MACI) cases reported in literature do not deal with rheumatoid knees and do not have a long clinical-histologic follow-up. We report about a 46-year old woman who suffered of a painful focal Outerbridge 4th degree chondral lesion in the medial femoral condyle of her left rheumatoid knee. The tissue defect was filled by a Cartilage Regeneration System (CaReS®) based on a type I collagen matrix seeded by autologous in vitro expanded chondrocytes. The patient was followed up to ten years clinically and by MRI, and finally treated with a Total Knee Replacement for the increasing arthritis. Histologically, the explanted MACI tissue showed an increased cellularity with an extracellular matrix rich of collagen and glycosaminoglicanes even though the overall architecture was different from the normal cartilage pattern. The case reported suggests that the main goal of treatment for chondropathy is the long lasting control of symptoms, while permanent restoration of normal anatomy is still impossible. Mesenchymal stem cells, that develop into joint tissues, show immunosuppressive and anti-inflammatory qualities, in vitro and in vivo, indicating a potential role for tissue engineering approaches in the treatment of rheumatic diseases. | |
28804691 | Combination of celecoxib (Celebrex(®)) and CD19 CAR-redirected CTL immunotherapy for the | 2017 | The nonsteroidal anti-inflammatory drug (NSAID) Celecoxib (Celebrex(®)) received Food and Drug Administration (FDA) approval in 1998 for treatment of osteoarthritis and rheumatoid arthritis, and in recent years, its use has been extended to various types of malignancies, such as breast, colon, and urinary cancers. To maintain the survival of malignant B cells, non-Hodgkin's Lymphoma (NHL) is highly dependent on inflammatory microenvironment, and is inhibited by celecoxib. Celecoxib hinders tumor growth interacting with various apoptotic genes, such as cyclooxygenase-2 (Cox-2), B-cell lymphoma 2 (Bcl-2) family, phosphor-inositide-3 kinase/serine-threonine-specific protein kinase (PI3K/Akt), and inhibitors of apoptosis proteins (IAP) family. CD19-redirected chimeric antigen-receptor (CD19 CAR) T cell therapy has shown promise in the treatment of B cell malignancies. Considering its regulatory effect on apoptotic gene products in various tumor types, Celecoxib is a promising drug to be used in combination with CD19 CAR T cell therapy to optimize immunotherapy of NHL. | |
28638685 | Carotid artery stiffness in Behçet's disease. | 2017 Jun | OBJECTIVE: Increased carotid arterial stiffness (CAS) is a predictor of subclinical early atherosclerosis as well as carotid intima-media thickness (cIMT). We aimed to determine CAS and cIMT in Behçet's disease (BD). MATERIAL AND METHODS: BD (n=49) and rheumatoid arthritis (RA) (n=64) patients and healthy controls (HC) (n=40) were included in the study. cIMT was measured. CAS indices, including arterial compliance (AC), arterial distensibility (AD), Young's elastic modulus (YEM), Peterson's elastic modulus (Ep), and β stiffness index (βSI) were measured based on the diameter-pressure relationship. RESULTS: When compared to the HC group, the mean cIMT was significantly higher in the RA group (p=0.033), but it was not higher in the BD group. The CAS indices, including AD, AC, Ep, and βSI were not significantly different among the study groups. Moreover, the cIMT and CAS indices were not significantly different between active (n=20) and inactive BD patients, and these indices were not correlated with the scores of disease activity. AD, AC and Ep were significantly lower in the BD patients with a positive pathergy reaction than in those with a negative reaction. CONCLUSION: These results suggest that BD does not directly lead to arterial stiffness or to an increase in cIMT. | |
28405135 | Severe Bone Marrow Suppression Accompanying Pulmonary Infection and Hemorrhage of the Dige | 2017 Jan | A 60-year-old male patient developed hyperpyrexia, cough, expectoration with blood-stained sputum, mouth ulcers, and suppurative tonsillitis after receiving 35 days of combination treatment with leflunomide (LEF) and low-dose methotrexate (MTX) for active rheumatoid arthritis. On admission, routine blood tests showed severe thrombocytopenia, agranulocytosis, and decreased hemoglobin concentration compared with the relatively normal results of 1 month previously during the first hospitalization. Chest radiography revealed inflammation in both lungs, and a fecal occult blood test was positive. Given this presentation, severe bone marrow suppression accompanying pulmonary infection and hemorrhage of the digestive tract associated with LEF and MTX combination therapy was diagnosed. After 28 days of symptomatic treatment, the patient's complications subsided gradually. This case highlighted that bone marrow suppression associated with MTX and LEF combination therapy could be very serious, even at a normal dose or especially at the beginning of treatment. MTX and LEF combination therapy should be used with caution or be limited in those with a history of pulmonary disease, hemorrhage of the digestive tract, or other relevant diseases. | |
27729225 | MicroRNA mediated network motifs in autoimmune diseases and its crosstalk between genes, f | 2017 Jan | Autoimmune diseases (AIDs) are incurable but suppressible diseases whose molecular mechanisms are yet to be elucidated. In this work, we selected five systemic autoimmune diseases such as Rheumatoid Arthritis (RA), Type 1 Diabetes (T1D), Inflammatory Bowel Disease (IBD), Autoimmune Thyroid Disease (ATD) and Systemic Lupus Erythematosus (SLE). Heterogeneous data such as miRNA, transcription factor (TF), target genes and protein-protein interactions involved in these AIDs were integrated to understand their roles at different functional levels of miRNA such as transcription initiation, gene regulatory network formation and post transcriptional regulation. To understand the functional characteristics of these complex biological networks, they can be simplified as network motifs (sub networks) and motif-motif interacting pairs (MMIs). The network motif patterns and motif-motif interacting pairs that occur for the selected five diseases were identified. To further understand the functional association between AIDs, functions and pathways were determined using gene set enrichment analysis and five selected immune signaling pathways (ISPs). The crosstalk within AIDs and between the immune signaling pathways (ISPs) could provide novel insights in deciphering disease mechanisms. This study represents the first investigation of miRNA-TF regulatory network for AIDs and its association with ISPs using sub-network motifs. |