scholarly journals Polyglandular Autoimmune Syndrome Triggered after CTLA-4 and PD-1L Immunotherapy Treatment

Reports ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Juan Luis Fernández-Morera ◽  
Alfredo Renilla González ◽  
Carmen Elena Calvo Rodríguez ◽  
Judit Romano-García

Background: CTLA-4 and PD-1L are novel immune checkpoint targets for cancer treatment with specific side effects such as autoimmune diseases. Less frequently, the presence of several autoimmune diseases in the same patient has been described. In this communication, we illustrate the case of a 45-year-old patient with a previous diagnosis of advanced cancer that, after starting treatment with this immunotherapy, developed in the following months autoimmune diabetes, lymphocytic hypophysitis, and a Hashimoto thyroiditis in an abrupt and intense manner that would correspond to an autoimmune polyglandular disease. Discussion: The activation of autoimmunity and associated diseases is increasing in parallel with augmented indication of these immunotherapeutic treatments in cancer patients. A closer follow-up of these patients could be necessary for an optimal approach to this type of pathology. Conclusions: Different autoimmune diseases can converge in the same patient when immunotherapy for cancer is indicated to boost immune response against tumor, caused by altering immune tolerance.

Author(s):  
Kevin J. Peine ◽  
Naihan Chen ◽  
Eric M. Bachelder ◽  
Kristy M. Ainslie

Autoimmune diseases are the result of an improper immune response towards a self-antigen. Predominantly, autoimmune diseases have been treated using therapies that suppress systemic immune responses, which can result in significant side-effects like increased risk of infection and cancer. Alternatively, induction of immune tolerance through antigen-specific therapies can inhibit disease-associated responses without systemic suppression. Previously, immune tolerance has been accomplished by soluble antigen delivery through oral, nasal or sublingual routes. However, these therapies have shown minimal success in clinical settings. In an attempt to increase the efficacy of these therapies, recent work has utilized microparticulate delivery vehicles for the induction of immune tolerance. Microparticles are capable of increasing the solubility and circulation of cargo. In addition, their ability to passively target macrophages and dendritic cells increases their capacity for modulating the immune response. Recent work has shown microparticles fabricated with disease-associated antigens have limited disease progression and severity in animal models of Multiple Sclerosis, Type 1 Diabetes and Rheumatoid Arthritis. Inhibition of disease progression has corresponded with an antigen-specific decrease in inflammatory responses. The emerging field of inducing tolerance through microparticle-based therapies can limit therapeutic side-effects and increase patient quality of life by providing for long-term suppression of autoimmune disorders without compromising systemic immune function.


Author(s):  
Kevin J. Peine ◽  
Naihan Chen ◽  
Eric M. Bachelder ◽  
Kristy M. Ainslie

Autoimmune diseases are the result of an improper immune response towards a self-antigen. Predominantly, autoimmune diseases have been treated using therapies that suppress systemic immune responses, which can result in significant side-effects like increased risk of infection and cancer. Alternatively, induction of immune tolerance through antigen-specific therapies can inhibit disease-associated responses without systemic suppression. Previously, immune tolerance has been accomplished by soluble antigen delivery through oral, nasal or sublingual routes. However, these therapies have shown minimal success in clinical settings. In an attempt to increase the efficacy of these therapies, recent work has utilized microparticulate delivery vehicles for the induction of immune tolerance. Microparticles are capable of increasing the solubility and circulation of cargo. In addition, their ability to passively target macrophages and dendritic cells increases their capacity for modulating the immune response. Recent work has shown microparticles fabricated with disease-associated antigens have limited disease progression and severity in animal models of Multiple Sclerosis, Type 1 Diabetes and Rheumatoid Arthritis. Inhibition of disease progression has corresponded with an antigen-specific decrease in inflammatory responses. The emerging field of inducing tolerance through microparticle-based therapies can limit therapeutic side-effects and increase patient quality of life by providing for long-term suppression of autoimmune disorders without compromising systemic immune function.


Author(s):  
M Horsey ◽  
P Hogan ◽  
T Oliver

Summary A 71-year-old woman with severe right lower leg pain, edema and erythema was presented to the Emergency Department and was found to have an extensive deep vein thrombosis (DVT) confirmed by ultrasound. She underwent an extensive evaluation due to her prior history of malignancy and new hypercoagulable state, but no evidence of recurrent disease was detected. Further investigation revealed pernicious anemia (PA), confirmed by the presence of a macrocytic anemia (MCV=115.8fL/red cell, Hgb=9.0g/dL), decreased serum B12 levels (56pg/mL), with resultant increased methylmalonic acid (5303nmol/L) and hyperhomocysteinemia (131μmol/L), the presumed etiology of the DVT. The patient also suffered from autoimmune thyroid disease (AITD), and both antithyroglobulin and anti-intrinsic factor antibodies were detected. She responded briskly to anticoagulation with heparin and coumadin and treatment of PA with intramuscular vitamin B12 injections. Our case suggests that a DVT secondary to hyperhomocystenemia may represent the first sign of polyglandular autoimmune syndrome III-B (PAS III-B), defined as the coexistent autoimmune conditions AITD and PA. It is important to recognize this clinical entity, as patients may not only require acute treatment with vitamin B12 supplementation and prolonged anticoagulation, as in this patient, but may also harbor other autoimmune diseases. Learning points A DVT can be the first physical manifestation of a polyglandular autoimmune syndrome. Hyperhomocysteinemia secondary to pernicious anemia should be considered as an etiology of an unprovoked DVT in a euthyroid patient with autoimmune thyroid disease. Patients with DVT secondary to hyperhomocysteinemia should undergo screening for the presence of co-existent autoimmune diseases in addition to treatment with B12 supplementation and anticoagulation to prevent recurrent thromboembolism.


2020 ◽  
pp. 40-43
Author(s):  
L. Sorrentino ◽  
L. Vergel ◽  
A. Hamaui ◽  
D. Dubinsky

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) is a condition in which exposure to an adjuvant leads to an aberrant immune response resulting in signs and symptoms of autoimmune diseases. We present the case of a patient with arthritis and palpable purpura after hyaluronic acid lip injection.


2006 ◽  
Vol 31 (5) ◽  
pp. 746-749 ◽  
Author(s):  
P. Amerio ◽  
M. Tracanna ◽  
P. De Remigis ◽  
C. Betterle ◽  
L. Vianale ◽  
...  

2019 ◽  
Vol 12 (8) ◽  
pp. e230760 ◽  
Author(s):  
Katherine Hoener ◽  
Tulsi Sharma

A 46-year-old woman was referred to the endocrinology clinic for evaluation of progressive fatigue, dizziness and treatment-resistant hypothyroidism. Initial laboratory results revealed hypothyroidism, hyponatraemia and hyperkalaemia. Liothyronine sodium (Cytomel) was initiated, which exacerbated her fatigue and dizziness. Suspecting adrenal insufficiency, an 08:00 cortisol level was obtained and found to be low with failure to increase following cosyntropin stimulation test. Diagnosis of primary adrenal insufficiency was confirmed via CT abdomen and pelvis revealing diminutive adrenal glands and elevated 21-hydroxylase antibody. Treatment was initiated with hydrocortisone 10 mg every morning and 5 mg at 16:00/day, with plan for patient follow-up in 3 weeks to assess need for mineralocorticoid replacement. Polyglandular syndromes are rare and have a wide variety of presentation. Thus, we recommend screening patients with a single autoimmune disorder who do not respond to conventional therapy to prevent possible life-threatening adrenal crisis.


2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Sean Linkes ◽  
Christopher Fry ◽  
Anthony Quinn

Following proper activation, naïve “CD4lo” T cells differentiate into effector T cells with enhanced expression of CD4 -“CD4hi” effectors. Autoimmune diabetes-prone NOD mice display a unique set of antigen-experienced “CD4lo” T cells that persist after primary stimulation. Here, we report that a population of such cells remained after secondary and tertiary TCR stimulation and produced cytokines upon antigenic challenge. However, when NOD blasts were induced in the presence of rIL-15, the number of antigen-experienced “CD4lo” T cells was significantly reduced. Clonal contraction, mediated in part by CD95-dependent activation-induced cell death (AICD), normally regulates the accumulation of “CD4hi” effectors. Interestingly, CD95 expression was dramatically reduced on the AICD-resistant NOD “CD4lo” T cells. Thus, while autoimmune disease has often been attributed to the engagement of robust autoimmunity, we suggest that the inability to effectively contract the immune response distinguishes benign autoimmunity from progressive autoimmune diseases that are characterized by chronic T cell-mediated inflammation.


2020 ◽  
Vol 48 ◽  
Author(s):  
Virgínia Pereira Monteiro ◽  
Alexandre Tavares Camelo Oliveira ◽  
Tiago Cunha Ferreira

Background: The pemphigus complex is defined as a group of blistering autoimmune diseases that affects skin and mucous membrane. Pemphigus foliaceous is the most common disease in this group, being characterized by the production of autoantibodies against keratinocyte adhesion molecules. The treatment is based on the use of immunosuppressive drugs and requires constant monitoring to assess inflammatory control as well as side effects of therapy. Based on that, the aim of this study was to report the clinical and laboratorial follow-up of a canine with pemphigus foliaceous.Case: An 11-year-old male neutered mongrel dog, weighing 9.8 kg, was presented with a main complaint related to disseminated pruritus and lesions in face, trunk and limbs. Dermatological examination revealed meliceric crusts, epidermal collars and diffuse pustules in inguinal, abdominal, face, limbs, ears and thoraco-lumbar regions. Cytological examination was performed, revealing inflammatory and acantholytic cells and absence of bacterial cells. Biopsy procedure revealed subcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatible with canine pemphigus foliaceous. Hemoto-biochemical analysis revealed a leukocytosis due to increased neutrophil count. Systemic treatment with high dose of prednisolone (2.0 mg/kg) and azathioprine (2.5 mg/kg) was proposed, while topical therapy with a 3% chlorhexidine shampoo was used to prevent secondary bacterial infections. The patient improved the dermatological clinical signs, being possible to observe a reduction of systemic and tissue inflammatory process. After 90 days of therapy, there was a partial loss of hair body coverage, associated with follicular lesions, and after 180 days of therapy it was possible to notice a new hair mantle, without visible areas of inflammation.Discussion: The described clinical case demonstrates the clinical and laboratorial follow-up of a patient with naturally occurring canine pemphigus foliaceus. The main clinical characteristic of this disease is the formation of generalized pustular lesions, affecting regions such as the head, ear pinnae and limbs, which induced the diagnostic suspicion in the reported patient, in addition to the clinical history associated with complementary exams. In tissue evaluation, a pyogranulomatous inflammatory process was observed, with a marked presence of neutrophils and macrophages, which migrate from the dermis towards the epidermis. In systemic leukocyte analysis, an increase in the total leukocyte count was observed, due to the increase in circulating neutrophils. The therapy was based in use of a high dose of prednisolone associated with azathioprine. The following hemato-biochemical evaluations revealed a gradual reduction of systemic inflammatory process. Attention is drawn to neutrophil to lymphocyte ratio, which is a low-cost biomarker and less sensitive to pathophysiological changes when compared to individual leukocyte count. This parameter has been gaining visibility as a potential method of monitoring chronic inflammatory diseases. In veterinary medicine, its use is limited, with no reports related to canine pemphigus foliaceous in Brazil. After clinical and hematological improvement, prednisolone dose was slowly reduced, in order to avoid side effects. After clinical improvement, only azathioprine was maintained, in order to prevent critical flares. This report provides a clinical and laboratorial follow-up of a canine with pemphigus foliaceous, as well as it is the first one to describe the use of neutrophil to lymphocyte ratio to monitor therapeutic progression. New studies and reports involving this biomarker in autoimmune diseases monitoring are encouraged.


2005 ◽  
Vol 11 ◽  
pp. 85
Author(s):  
Allison Elise Kerr ◽  
Wolali Odonkor ◽  
Gail Nunlee-Bland ◽  
Juanita Archer ◽  
Anitha Kolukula ◽  
...  

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