Endocrine Risk Factors for COVID-19 in Context of Aging

Aged people are the most susceptible group to COVID-19 infection. Immunosenescence characterized by impairment of immune function with inflamm-aging contributes to pathophysiological alterations, among which endocrine and metabolic diseases are not exception. Diabetes, obesity along with impairment of disorders of thyroid functions are the most frequent ones, the common feature of which is failure of immune system including autoimmune processes. In the minireview we discussed how COVID-19 and aging impact innate and adaptive immunity, diabetes and selected neuroendocrine processes. Mentioned is also beneficial effect of vitamin D for attenuation of these diseases and related epigenetic issues. Particular attention is devoted to the role of ACE2 protein in the light of its intimate link with renin-angiotensin regulating system.

B Cell Involvement in the Pathogenesis of Ankylosing Spondylitis

Extensive research into ankylosing spondylitis (AS) has suggested the major role of genetics, immune reactions, and the joint–gut axis in its etiology, although an ultimate consensus does not yet exist. The available evidence indicates that both autoinflammation and T-cell-mediated autoimmune processes are actively involved in the disease process of AS. So far, B cells have received relatively little attention in AS pathogenesis; this is largely due to a lack of conventional disease-defining autoantibodies. However, against prevailing dogma, there is a growing body of evidence suggestive of B cell involvement. This is illustrated by disturbances in circulating B cell populations and the formation of auto-reactive and non-autoreactive antibodies, along with B cell infiltrates within the axial skeleton of AS patients. Furthermore, the depletion of B cells, using rituximab, displayed beneficial results in a subgroup of patients with AS. This review provides an overview of our current knowledge of B cells in AS, and discusses their potential role in its pathogenesis. An overarching picture portrays increased B cell activation in AS, although it is unclear whether B cells directly affect pathogenesis, or are merely bystanders in the disease process.

Correlates of survival after autoantibody reduction therapy for acute IPF exacerbations

Background No medical treatment has proven efficacy for acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF), and this syndrome has a very high mortality. Based on data indicating humoral autoimmune processes are involved in IPF pathogenesis, we treated AE-IPF patients with an autoantibody reduction regimen of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin. This study aimed to identify clinical and autoantibody determinants associated with survival after autoantibody reduction in AE-IPF. Methods Twenty-four(24) AE-IPF patients received the autoantibody reduction regimen. Plasma anti-epithelial autoantibody titers were determined by HEp-2 indirect immunofluorescence assays in 22 patients. Results Mean age of the patients was 70 + 7 years old, and 70% were male. Beneficial clinical responses that occurred early during therapy were a favorable prognostic indicator: supplemental O2 flows needed to maintain resting SaO2>92% significantly decreased and/or walk distances increased among all 10 patients who survived for at least one year. Plasma anti-HEp-2 autoantibody titers were ~-three-fold greater in survivors compared to non-survivors (p<0.02). Anti-HEp-2 titers >1:160 were present in 75% of the evaluable one-year survivors, compared to 29% of non-survivors, and 10 of 12 patients (83%) with anti-HEP-2 titers <1:160 died during the observation period (Hazard Ratio = 3.3, 95% Confidence Interval = 1.02–10.6, p = 0.047). Conclusions Autoantibody reduction therapy is associated with rapid reduction of supplemental oxygen requirements and/or improved ability to ambulate in many AE-IPF patients. Facile anti-epithelial autoantibody assays may help identify those most likely to benefit from these treatments.

Indoleamine-2,3-Dioxygenase as a Perioperative Marker of the Immune System

Indoleamine-2,3-dioxygenase (IDO) is the “rate-limiting” enzyme in the kynurenine (Kyn) pathway of the tryptophan (Trp) catabolism. By its immune-modulatory effect, IDO initiates changes to the physiologically balanced immune state and plays a key role in the pathogenesis of various diseases, as well as in the perioperative setting during surgery. In autoimmune processes, highly malignant cancers such as glioblastoma or organ transplantation, IDO’s involvement has been studied extensively. However, in severe systemic infections, as present in sepsis, it is not yet completely understood. Hereafter, in this narrative review, we present the current knowledge of IDO’s implication on such complex immune-related processes. Moreover, we address the role of IDO as a predictive biomarker as well as a therapeutic target for immune-mediated diseases. Finally, we discuss IDO in the setting of surgical trauma-induced stress and highlight its promising use as a biomarker in the pre-operative setting for all disciplines involved in the decision-making process and treatment of patients undergoing surgery.

Glaucoma is an autoimmune disease

Glaucoma is one of the most serious diseases that affects millions of people around the world, but the pathogenesis of this disease is not completely clear. Once the only mechanism for the development of this disease was considered to be an increase in IOP. Current research indicates that the pathogenesis of glaucoma depends on several interacting mechanisms, which include: mechanical damage due to increased IOP, hypoxia, excitotoxicity, oxidative stress, and the involvement of autoimmune processes. Antibody changes in glaucoma patients have been described, but it is still unclear whether the autoantibodies observed in glaucoma are epiphenomenal or cause of the disease. Key words: glaucoma, glaucoma pathogenesis, autoimmunity, autoimmune glaucoma.

Sjögren-related cardiomyopathy presenting with cardiogenic shock

Previous reports have described non-ischaemic cardiomyopathy related to a variety of autoimmune diseases. However, very few case reports describe Sjögren disease as a contributing factor to cardiomyopathy. We report the case of a 69-year-old woman with a history of Sjögren disease who presented with cardiogenic shock. Laboratory testing and cardiac MRI revealing apical septal late gadolinium enhancement were consistent with an autoimmune aetiology. After ruling out ischaemic, infectious and other possible causes, the patient’s clinical presentation was thought to be related to underlying Sjögren disease. She was treated with intravenous steroids and evidence-based heart failure therapy, but she eventually died after having declined heart transplantation. Given the rarity of Sjögren disease, no diagnostic criteria or standard treatment has been established for cardiomyopathy related to this disease. Diagnosis should be considered in patients who show evidence of autoimmune processes after other possible causes are ruled out.

Immune Checkpoint Inhibitors and the Heart

Immune checkpoint inhibitors (ICIs) represent a break-through treatment for a large number of cancer types. This treatment is increasingly being recommended. ICIs are prescribed for primary tumours and for metastases, adjuvant/neo-adjuvant therapy. Thus, there is an increased need for expertise in the field, including the ways of response and toxicities related to them. ICIs become toxic because of the removal of self-tolerance, which in turn induces autoimmune processes that affect every organ. However, when relating to the heart, it has been noticed to be leading to acute heart failure and even death caused by various mechanisms, such as: myocarditis, pericarditis, arrhythmia, and Takotsubo cardiomyopathy. This review aims to address the above issues by focusing on the latest findings on the topic, by adding some insights on the mechanism of action of ICIs with a special focus on the myocardial tissue, by providing information on clinical manifestations, diagnosis and (wherever possible) treatment of the cardiotoxic events related to this therapy. The information is expanding and in many cases, the articles we found refer mainly to case-presentations and studies conducted on small populations. However, we consider that it is worthwhile to raise awareness of this new treatment, especially since it is widely now and it provides a significant increase in the survival rate in patients who receive it.

Morphological justifi cation of the pathogenesis of angleclosure glaucoma

Objective. To prove the role of interrelated autoimmune, hemostatic and infl ammatory mechanisms in the pathogenesis of angleclosure glaucoma on the basis of experimental morphological research. Material and methods. The work was performed on 3 denucleated eyes of patients with terminal “creeping” angle-closure glaucoma (ACG) and 2 eyes with terminal ACG during an intractable acute exacerbation. Sagittal sections through the area of Schlemm’s canal, as well as serial cross sections, were examined by the method of paraffi n sections stained with hematoxylin-eosin (HE). To assess the degree of the infl ammatory response in the eye tissues, the density of infl ammatory cells was calculated within the standard eyepiece micrometer grid at a magnifi cation of × 20.Results. The formation of peripheral anterior synechiae between the periphery of the iris and the trabecular meshwork in the iridocorneal angle is the main etiological factor in chronic angle closure. Several mechanisms contribute to the formation of anterior synechiae. First of all, in our opinion, it is autoimmune infl ammation. Edema and hyperemia of the ciliary processes pushes the iris anteriad, collagen fi bers of the trabecular meshwork are damaged; delayed endothelialization of the trabecular plate occurs, and the angle of the anterior chamber narrows and closes as a result. The resistance to the outfl ow of intraocular fl uid increases. Ischemia, due to increased intraocular pressure (IOP), causes the formation of new vessels in the iris, where aggregates of blood cells are observed. The walls of the newly formed vessels are defective, which contributes to hemorrhages. Thus, in addition to autoimmune infl ammation, we observe signs of endothelial dysfunction syndrome associated with infl ammatory processes with ACG.Conclusions. 1. The pathogenesis of chronic angleclosure glaucoma is based on autoimmune processes, as proved by lymphocytoplasmocytic infl ammatory infi ltration with an addition of pigment-containing macrophages and fi broblasts at the junction of the iris with the cornea. 2. The detection of intravascular aggregates is a proof of impaired hemostasis in angle-closure glaucoma. 3. Parietal thrombus formation in the newly formed vessels of the iris, fi brin in the tissues are evidence of chronic endothelial dysfunction in ACG. 4. The capillaries of the ciliary processes surrounded by a fi brin ring indicate an acute vasomotor disorder and the release of plasma containing fi brinogen into the surrounding tissue. This is indirect evidence of emotional and vasomotor instability in patients with this form of glaucoma. 5. Disturbances in the systems of immunity and hemostasis are interrelated processes. 6. Increased iris stiff ness is ACG biomarker and may serve as a further target for therapeutic intervention.