Check point autoimmunity

INTRODUCTION: The autoimmune response in type 1 diabetes (T1D), in which the beta cells expressing aberrant or modified proteins are killed, resembles an effective antitumor response. Defective ribosomal protein products in tumors are targets of the anti-tumor immune response that is unleashed by immune checkpoint inhibitor (ICI) treatment in cancer patients. We recently described a defective ribosomal product of the insulin gene (INS-DRiP) that is expressed in stressed beta cells and targeted by diabetogenic T cells...

High endothelial venules (HEVs), high walled cuboidal blood vessels, through their expression of adhesion molecules and chemokines, allow the entrance of lymphoid cells into primary, secondary, and tertiary lymphoid structures (aka tertiary lymphoid organs). HEV heterogeneity exists between various lymphoid organs in their expression of peripheral node addressin (PNAd) and mucosal vascular addressin adhesion molecule 1(MAdCAM-1). Transcriptomic analyses reveal extensive heterogeneity, plasticity, and regulation of HEV gene expression in ontogeny, acute inflammation, and chronic inflammation within and between lymphoid organs...

Zieve's syndrome, associated with chronic alcoholism, manifests as hemolytic anemia, transient hyperlipidemia, and cholestatic jaundice. Key symptoms comprise nausea, abdominal pain, and jaundice. Diagnosis relies on recognizing the triad in those with an alcohol use history. Supportive management includes blood transfusions and alcohol cessation. The exact pathophysiology remains uncertain, with hypotheses ranging from alcohol-induced liver damage to autoimmune processes. The report emphasizes diagnostic complexities, particularly when concurrent with autoimmune disorders such as latent autoimmune diabetes of adults or complicated by disseminated intravascular coagulation (DIC)...

BACKGROUND: Immune checkpoint inhibitors (ICI) are promising treatment options for various cancers. However, their use is associated with immune-related adverse events (irAEs), including ICI-induced diabetes mellitus (ICI-DM). This study aimed to investigate the clinical features of ICI-DM, with a particular focus on alterations to pancreatic volume. METHODS: We conducted a retrospective review of 2829 patients who received ICI treatment at the Chang Gung Memorial Hospital, Linkou, between January 2014 and December 2021...

INTRODUCTION/AIMS: Myasthenia gravis (MG) is a rare, life-threatening immune-related adverse effect (irAE) of immune checkpoint inhibitor (ICI) treatment. C5-complement inhibitors are effective treatments for acetylcholine receptor antibody (AChR ab) positive generalized MG. We describe the use of eculizumab/ravulizumab in two patients with MG receiving concomitant pembrolizumab. METHODS: This was a retrospective review of two medical records. RESULTS: Patient 1: An 80-year-old male with recurrent, non-muscle invasive transitional cell carcinoma of the bladder developed ICI-induced AChR ab positive MG (ICI-MG), myositis, and myocarditis 2 weeks after the first dose of pembrolizumab...

BACKGROUND AND OBJECTIVES: The factors that drive progression in multiple sclerosis (MS) remain obscure. Identification of key properties of meningeal inflammation will contribute to a better understanding of the mechanisms of progression and how to prevent it. METHODS: Applying single-cell RNA sequencing, we compared gene expression profiles in immune cells from meningeal ectopic lymphoid tissue (mELT) with those from secondary lymphoid organs (SLOs) in spontaneous chronic experimental autoimmune encephalomyelitis (EAE), an animal model of MS...

Primary Sjögren's syndrome (pSS) is known as autoimmune disease characterized by damage to endocrine glands, such as the salivary and lacrimal glands. This study aimed to identify potential biomarkers for pSS using integrated bioinformatics analysis and explore the relationship between differentially expressed genes (DEGs) and immune infiltration. Three pSS datasets (GSE7451, GSE23117, and GSE40611) from the gene expression omnibus database were integrated. All the datasets were processed in R (version 4...

Background and Objectives. Coeliac disease is an autoimmune disorder provoked by a dietary group of proteins called gluten in genetically predisposed individuals. Over the past several decades, the prevalence of coeliac disease has been steadily growing and it is now recognized to be occurring worldwide. The prevalence varies greatly between ethnic, racial groups and regionally. Such variability makes local epidemiological studies important for spreading awareness and setting a threshold for suspicion of coeliac disease...

Immune checkpoint inhibitors are becoming more commonly used for many forms of malignancy. With this class of medications being more heavily used, there has been an associated rise in medication-induced autoimmune hepatitis. This case involves a 35-year-old woman being treated with nivolumab/ipilimumab for renal cell carcinoma who developed a steroid-refractory autoimmune hepatitis.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried. OBJECTIVES: To assess the effects of treatments for bullous pemphigoid. SEARCH METHODS: We updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase...

Immune checkpoint inhibitor therapies act through blockade of inhibitory molecules involved in the regulation of T cells, thus releasing tumor specific T cells to destroy their tumor targets. However, immune checkpoint inhibitors (ICI) can also lead to a breach in self-tolerance resulting in immune-related adverse events (irAEs) that include tissue-specific autoimmunity. This review addresses the question of whether the mechanisms that drive ICI-induced irAEs are shared or distinct with those driving spontaneous autoimmunity, focusing on ICI-induced diabetes, ICI-induced arthritis, and ICI-induced thyroiditis due to the wealth of knowledge about the development of autoimmunity in type 1 diabetes, rheumatoid arthritis, and Hashimoto's thyroiditis...

OBJECTIVE: It has been suggested that non-uterine endometrial implants can express thyroid-stimulating hormone receptors, thus inducing the formation of thyroid-stimulating immunoglobulin. We aimed to compare the autoantibody positivity in patients with and without endometriosis and to determine whether there is a difference in the incidence of thyroid diseases. METHODS: This prospective observational study was conducted on 102 women who had been operated on for benign gynecological diseases...

A variety of inflammatory conditions may directly involve the endocrine glands, leading to endocrine dysfunction that can cause severe consequences on patients' health, if left untreated. Inflammation of the endocrine system may be caused by either infectious agents or other mechanisms, including autoimmune and other immune-mediated processes. Not infrequently, inflammatory and infectious diseases may appear as tumor-like lesions of endocrine organs and simulate neoplastic processes. These diseases may be clinically under-recognized and not infrequently the diagnosis is suggested on pathological samples...

UNLABELLED: A Prospective Study to Evaluate the Possible Role of Cholecalciferol Supplementation on Autoimmunity in Hashimoto's Thyroiditis Biva Bhakat1 , Jyotirmoy Pal2 , Sukdeb Das3 , Sumit Kr Charaborty4 1,3Nil Ratan Sircar Medical College, Kolkata, 2 RG Kar Medical College and Hospital, 4 North Bengal Medical College, Siliguri Introduction: Hashimoto thyroiditis (HT) is an autoimmune disease that destroys thyroid cells by antibody and call-mediated immune processes. Hashimoto thyroiditis is the commonest cause of goitre in iodine-sufficient regions...

Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). (1) Objective: To explore the association between CTLA-4 single nucleotide polymorphisms (SNP) and risk to (CRC) in the Saudi population. (2) Methods: In this case-control study, 100 patients with CRC and 100 matched healthy controls were genotyped for three CTLA-4 SNPs: rs11571317 (-658C > T), rs231775 (+49A > G) and rs3087243 (CT60 G > A), using TaqMan assay method...

A 58-year-old woman developed new-onset recurrent ascites after the recent initiation of cemiplimab for the treatment of advanced basal cell carcinoma. A comprehensive serological workup for viral, metabolic, and autoimmune causes was unrevealing. Transjugular liver biopsy demonstrated parenchymal changes consistent with a diagnosis of sinusoidal obstruction syndrome. While this is a condition commonly observed in patients after hematopoietic stem cell transplantation or use of chemotherapeutic agents, it should also be considered in patients who develop new-onset liver dysfunction after the initiation of checkpoint inhibitors...

BACKGROUND: Following the introduction of the COVID-19 vaccines, there has been uncertainty as to whether receiving the COVID-19 vaccine will result in overactivation of the immune system and subsequently lead to an autoimmune disease flare.The purpose of this study was to assess whether rheumatoid arthritis (RA) patients who received the mRNA COVID-19 vaccine are at increased risk for disease flare. METHODS: We conducted a single-center retrospective and prospective study at the Louis Stokes Cleveland VA Medical Center between 12/2021 and 2/2022...

Biological agents have in the last two decades become very important therapeutic agents, particularly for the treatment of various autoimmune disorders. The most widely used biologics are the tumor necrosis factor-α (TNF-α) receptor antagonists: infliximab, adalimumab, and etanercept. Other commonly used biological agents are interleukin (IL)-1 receptor antagonist (Anakinra), interleukin (IL)-6 receptor antagonist (tocilizumab), and CD20 surface antigen antagonist (rituximab). The current review will however focus on TNF-α receptor antagonists...

The B cell antigen receptor (BCR)-repertoire is capable of recognizing a nearly unlimited number of antigens. Inevitably, the random nature of antibody gene segment rearrangement, needed in order to provide mature B cells, will generate autoreactive specificities. Once tolerance mechanisms fail to block the activation and differentiation of autoreactive B cells, harmful autoantibodies may get secreted establishing autoimmune diseases. Besides the hallmark of autoimmunity, namely IgG autoantibodies, IgM autoantibodies are also found in many autoimmune diseases...

No abstract text is available yet for this article.