Autoimmune diseases and their relation with immunological, neurological and endocrinological axes

Coronel-Restrepo, Nicolás; Posso-Osorio, Iván; Naranjo-Escobar, Juan; Tobón, Gabriel J.

doi:10.1016/j.autrev.2017.05.002

Cited by 36 publications

(16 citation statements)

References 137 publications

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“…This suggests that pubertal hormonal changes in women may alter the milieu of the autoimmune response and make it more amenable to treatment with 4R+3Dex. 29 The hormonal changes and relatively immunosuppressed state in female patients during reproductive age seems to influence response to this therapy. These findings are consistent with similar findings of the impact on response in adults with ITP of the combination of female sex and shorter duration of ITP.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Children with Persistent and Chronic Idiopathic Thrombocytopenic Purpura: 4 Infusions of Rituximab and Three 4-Day Cycles of Dexamethasone

Oved

Lee

Bussel

2017

The Journal of Pediatrics

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Objectives To assess initial and long-term outcome of children with persistent/chronic idiopathic thrombocytopenic purpura (ITP) treated with 4 infusions of rituximab and three 4-day cycles of dexamethasone (4R+3Dex) including cohorts with most benefit and/or treatment associated toxicity. Study design All pediatric patients with ITP at Weill-Cornell who received 4R+3Dex were included in this retrospective study. Duration was median time from first rituximab infusion to treatment failure. Patient cohort included 33 children ages 1-18 years with persistent/chronic ITP; 19 were female, 10 of whom were adolescents. Every patient had failed more than 1 and usually several ITP treatments. Results Children were treated with rituximab, 375 mg/m2 weekly for 4 weeks and three 4-day courses of dexamethasone 28 mg/m2 (40 mg max). Average age of nonresponders was 7.75 years, and initial responders averaged 12.7 years (P =.0073); 30% maintained continuing response at 60 months or last check-up. Eight of the 10 patients who underwent remission were female with ITP <24 months prior to initiating 4R+3Dex. All responding male patients except 2 relapsed. Conclusions Durable unmaintained ITP remission after 4R+3Dex was seen almost exclusively in female adolescents with <24 months duration of ITP. This provides a new therapeutic paradigm for a subpopulation with hard-to-treat chronic ITP. The pathophysiology of ITP underlying this distinction requires further elucidation.

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Section: Discussionmentioning

confidence: 99%

Treatment of Children with Persistent and Chronic Idiopathic Thrombocytopenic Purpura: 4 Infusions of Rituximab and Three 4-Day Cycles of Dexamethasone

Oved

Lee

Bussel

2017

The Journal of Pediatrics

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“…These diseases include both tissue-specific and systemic disorders and affect approximately 3–5% of the population ( 1 , 2 ). Most of the autoimmune diseases are heterogeneous in nature and are usually characterized by the expression of autoantibodies, pro-inflammatory cytokines, and autoreactive T-cells ( 3 , 4 ). Many theories have suggested that a genetic predisposition is the main cause of autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

IRE1α Implications in Endoplasmic Reticulum Stress-Mediated Development and Pathogenesis of Autoimmune Diseases

et al. 2018

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Inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) is the most prominent and evolutionarily conserved endoplasmic reticulum (ER) membrane protein. This transduces the signal of misfolded protein accumulation in the ER, named as ER stress, to the nucleus as “unfolded protein response (UPR).” The ER stress-mediated IRE1α signaling pathway arbitrates the yin and yang of cell life. IRE1α has been implicated in several physiological as well as pathological conditions, including immune disorders. Autoimmune diseases are caused by abnormal immune responses that develop due to genetic mutations and several environmental factors, including infections and chemicals. These factors dysregulate the cell immune reactions, such as cytokine secretion, antigen presentation, and autoantigen generation. However, the mechanisms involved, in which these factors induce the onset of autoimmune diseases, are remaining unknown. Considering that these environmental factors also induce the UPR, which is expected to have significant role in secretory cells and immune cells. The role of the major UPR molecule, IRE1α, in causing immune responses is well identified, but its role in inducing autoimmunity and the pathogenesis of autoimmune diseases has not been clearly elucidated. Hence, a better understanding of the role of IRE1α and its regulatory mechanisms in causing autoimmune diseases could help to identify and develop the appropriate therapeutic strategies. In this review, we mainly center the discussion on the molecular mechanisms of IRE1α in the pathophysiology of autoimmune diseases.

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“…Although cytokine antagonists have altered the course of many ADs, most current therapeutic agents target the terminal phase of inflammation and do not address the fundamental problems that are responsible for the initiation and progression of the autoimmune process (15). ADs are often characterized by chronic conditions, which in most cases require sustained, even life-long treatment, which imposes a heavy strain and financial burden on patients and significantly increases their risk of malignant tumors and infectious complications (21)(22)(23). As cell immune therapy technology can induce immune tolerance through various immunosuppressive pathways and is expected to achieve longterm relief of the disease (24)(25)(26), it is becoming a promising technology in the field of immune tolerability.…”

Section: Immune Homeostasismentioning

confidence: 99%

“…A simple hypothesis that has been put forward to explain the pathogenesis of autoimmune disease is that polymorphisms in various genes result in defective regulation or reduced thresholds for lymphocyte activation, and environmental factors initiate or augment the activation of self-reactive lymphocytes that have escaped control and are poised to react against self-constituents (15). A combination of triggering factors leads to the diversity of immune disorders, including cellular immunity, humoral immunity, neuroendocrine networks, and cytokine networks (21). There are individual differences in immune disorder indicators among different patients, and the immune disorder status of the same patient can change as the AD progresses, presenting a difficult clinical challenge for the treatment of complex, individualized conditions.…”

Section: Cell Therapy Approaches To Adsmentioning

confidence: 99%

Prospects of the Use of Cell Therapy to Induce Immune Tolerance

et al. 2020

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Conditions in which abnormal or excessive immune responses exist, such as autoimmune diseases (ADs), graft-versus-host disease, transplant rejection, and hypersensitivity reactions, are serious hazards to human health and well-being. The traditional immunosuppressive drugs used to treat these conditions can lead to decreased immune function, a higher risk of infection, and increased tumor susceptibility. As an alternative therapeutic approach, cell therapy, in which generally intact and living cells are injected, grafted, or implanted into a patient, has the potential to overcome the limitations of traditional drug treatment and to alleviate the symptoms of many refractory diseases. Cell therapy could be a powerful approach to induce immune tolerance and restore immune homeostasis with a deeper understanding of immune tolerance mechanisms and the development of new techniques. The purpose of this review is to describe the current panoramic scope of cell therapy for immune-mediated disorders, discuss the advantages and disadvantages of different types of cell therapy, and explore novel directions and future prospects for these tolerogenic therapies.

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Autoimmune diseases and their relation with immunological, neurological and endocrinological axes

Cited by 36 publications

References 137 publications

Treatment of Children with Persistent and Chronic Idiopathic Thrombocytopenic Purpura: 4 Infusions of Rituximab and Three 4-Day Cycles of Dexamethasone

Treatment of Children with Persistent and Chronic Idiopathic Thrombocytopenic Purpura: 4 Infusions of Rituximab and Three 4-Day Cycles of Dexamethasone

IRE1α Implications in Endoplasmic Reticulum Stress-Mediated Development and Pathogenesis of Autoimmune Diseases

Prospects of the Use of Cell Therapy to Induce Immune Tolerance

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