Histocompatibility and Reproduction: Lessons from the Anglerfish

Reproduction in certain deep-sea anglerfishes involves the permanent attachment of dwarf males to much larger females and fusion of their tissues leading to the establishment of a shared circulatory system. This unusual phenomenon of sexual parasitism enables anglerfishes to maximize reproductive success in the vast and deep oceans, where females and males otherwise rarely meet. An even more surprising phenomenon relates to the observation that joining of genetically disparate male and female anglerfishes does not evoke a strong anti-graft immune rejection response, which occurs in vertebrates following allogeneic parabiosis. Recent studies demonstrated that the evolutionary processes that led to the unique mating strategy of anglerfishes coevolved with genetic changes that resulted in loss of functional genes encoding critical components of the adaptive immune system. These genetic alterations enabled anglerfishes to tolerate the histoincompatible tissue antigens of their mate and prevent the occurrence of reciprocal graft rejection responses. While the exact mechanisms by which anglerfishes defend themselves against pathogens have not yet been deciphered, it is speculated that during evolution, anglerfishes adopted new immune strategies that compensate for the loss of B and T lymphocyte functions and enable them to resist infection by pathogens.

The Role of Exposomes in the Pathophysiology of Autoimmune Diseases I: Toxic Chemicals and Food

Autoimmune diseases affect 5–9% of the world’s population. It is now known that genetics play a relatively small part in the pathophysiology of autoimmune disorders in general, and that environmental factors have a greater role. In this review, we examine the role of the exposome, an individual’s lifetime exposure to external and internal factors, in the pathophysiology of autoimmune diseases. The most common of these environmental factors are toxic chemicals, food/diet, and infections. Toxic chemicals are in our food, drink, common products, the air, and even the land we walk on. Toxic chemicals can directly damage self-tissue and cause the release of autoantigens, or can bind to human tissue antigens and form neoantigens, which can provoke autoimmune response leading to autoimmunity. Other types of autoimmune responses can also be induced by toxic chemicals through various effects at the cellular and biochemical levels. The food we eat every day commonly has colorants, preservatives, or packaging-related chemical contamination. The food itself may be antigenic for susceptible individuals. The most common mechanism for food-related autoimmunity is molecular mimicry, in which the food’s molecular structure bears a similarity with the structure of one or more self-tissues. The solution is to detect the trigger, remove it from the environment or diet, then repair the damage to the individual’s body and health.

Macroautophagy in lymphatic endothelial cells inhibits T cell–mediated autoimmunity

Lymphatic endothelial cells (LECs) present peripheral tissue antigens to induce T cell tolerance. In addition, LECs are the main source of sphingosine-1-phosphate (S1P), promoting naive T cell survival and effector T cell exit from lymph nodes (LNs). Autophagy is a physiological process essential for cellular homeostasis. We investigated whether autophagy in LECs modulates T cell activation in experimental arthritis. Whereas genetic abrogation of autophagy in LECs does not alter immune homeostasis, it induces alterations of the regulatory T cell (T reg cell) population in LNs from arthritic mice, which might be linked to MHCII-mediated antigen presentation by LECs. Furthermore, inflammation-induced autophagy in LECs promotes the degradation of Sphingosine kinase 1 (SphK1), resulting in decreased S1P production. Consequently, in arthritic mice lacking autophagy in LECs, pathogenic Th17 cell migration toward LEC-derived S1P gradients and egress from LNs are enhanced, as well as infiltration of inflamed joints, resulting in exacerbated arthritis. Our results highlight the autophagy pathway as an important regulator of LEC immunomodulatory functions in inflammatory conditions.

Clinical significance of detecting organ-specificsensitization in patients with long-term chronic posttraumatic uveitis

Purpose: to assess the clinical significance of detecting organ-specific sensitization in chronic posttraumatic uveitis (CPTU) based on a comparative analysis of data from the leukocyte migration inhibition test (LMIT) and histological examination.Materials and methods. We examined 54 patients aged 17-82 with CPTU who underwent surgical removal of the eyeball (by enucleation/evisceration). To detect organ-specific sensitization, the LMIT in whole blood with extracts of corneal, lens, and uvearetinal tissue antigens was used. The eyes were subjected to histological examination after removal.Results. A positive response in LMIT was detected in 35.2 % of patients with CPTU. Pathomorphological signs of immune inflammation were found in 55.5 % of cases (30 eyes). In 23 eyes (42.6 %), the morphological picture was characterized by atrophic, fibrous and dystrophic changes in tissues. Based on the data from a comparative analysis of LMIT results and histological studies, we showed that in 16 cases out of 30 (53.3 %), morphologically confirmed immune inflammation was accompanied by sensitization to antigens of eye shells.Conclusions. In half of the cases, a productive inflammation, detected in CPTU during histological examination, was associated with the development of specific sensitization to eye tissue antigens. This result is important and should be considered when choosing how the patient should be managed, including targeted diagnostics and immunotropic therapy. The negative organ-specific response of LMIT in patients with chronic CPTU and intraocular inflammation confirmed by pathomorphological signs suggests a possible involvement of additional mechanisms of the inflammatory process, which requires further research.

The autoreactivity phenomenon in the pathogenesis of asthma-COPD overlap (ACO)

The modern concept of development of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) implies the leading role of immune reactions with the true inflammatory autoimmune pathogenetic components. Aim of the study was to evaluate the autoreactivity in patients with chronic immune-mediated respiratory diseases: BA, COPD, and their combination — ACO. Methods. The study enrolled 155 patients with the average age of 49 ± 17 years old. We modified quantitative ELISA for detection of IgE and IgG4-autoantibodies using commercial tissue antigens of epithelial keratin, type III and VI collagen, myosin and elastin (Sigma, USA), conjugates of monoclonal anti-IgE or anti-IgG4 antibodies and IgE and IgG4 reference reagents (Dr. Fooke, Germany). Results. Concomitant COPD and BA symptoms were accompanied by significantly higher levels of IgE autoAbs to epithelial keratin, type III and VI collagen and myosin and were associated with a higher detection rate of these Abs, especially in severe forms of the disease (50 — 80%). The IgE-autoAbs to myosin increased in individuals with ACO as compared to BA and reached the maximum values in patients with COPD. There was an opposite trend: the frequency of detection and concentration of IgG4-autoAbs decreased with the disease severity. The levels of IgG4-autoAbs to type III and IV collagens and to elastin decreased as the obstruction worsened and were undetectable in patients with COPD and ACO. IgE and IgG4 autoAbs were inversely correlated to type VI collagen, type III collagen, elastin and myosin (r = -0.38; -0.61). The spirometry showed the inverse correlations between the increased IgE-autoAbs to type III collagen and high-speed ventilation parameters (R = -0.79; p = 0.01). So, IgE-autoAbs may be considered a factor of the progressive course of BA in combination with COPD associated with a significant bronchial obstruction. Conclusion. Thus, the detection of IgE and IgG4-AT to tissue antigens of collagen, elastin and myosin can be further used for clinical and immunological monitoring of BA and COPD, especially with their combined phenotype (ACO). The increased levels of IgE-autoAbs can be considered one of the immunological prognostic markers of intense remodeling processes in the bronchial wall. These processes are also confirmed by an increased IgE-mediated immune response to miosine and elastine EG in patients with the severe disease. The developed assay of the level of autoAbs to tissue antigens can be used in the early diagnostics of adverse course of asthma, especially ACO, and can be used as a laboratory criterion of the control over the disease when making decisions on personalized pharmacotherapy and patient management.

Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases. Very recently, human monoclonal antibodies were approved for use on patients with COVID-19. The human monoclonal antibodies used in this study are almost identical with these approved antibodies. Thus, our results can establish the potential risk for autoimmunity and multi-system disorders with COVID-19 that may come from cross-reactivity between our own human tissues and this dreaded virus, and thus ensure that the badly-needed vaccines and treatments being developed for it are truly safe to use against this disease.

Immunohistochemistry as an important tool for exploring the insights of various aspects of gastro-intestinal tract

The concepts in immunology and techniques in histology have come together in a novel way to create a pioneering discipline known as ImmunoHistoChemistry (IHC), to discover new ways in detecting cell and tissue antigens related to amino acids, proteins and infectious agents by using labeled antibodies. These amalgamation techniques are applied in the disciplines of endocrinology, entero-biology, neurobiology, pathology, tumor biology and pharmaceutical research as a diagnostic tool. The simultaneous advancements in the field of imaging techniques further assisted and widened the application of IHC in molecular studies, thereby facilitating the development of novel therapeutic strategies. This paper attempts to discuss the different aspects of gastro-intestinal tract in relation to its cellular diversity, cellular differentiation, physiology and pathology, through the application of IHC methods.

The structure of a family 110 glycoside hydrolase provides insight into the hydrolysis of α-1,3-galactosidic linkages in λ-carrageenan and blood group antigens

α-Linked galactose is a common carbohydrate motif in nature that is processed by a variety of glycoside hydrolases from different families. Terminal Galα1–3Gal motifs are found as a defining feature of different blood group and tissue antigens, as well as the building block of the marine algal galactan λ-carrageenan. The blood group B antigen and linear α-Gal epitope can be processed by glycoside hydrolases in family GH110, whereas the presence of genes encoding GH110 enzymes in polysaccharide utilization loci from marine bacteria suggests a role in processing λ-carrageenan. However, the structure–function relationships underpinning the α-1,3-galactosidase activity within family GH110 remain unknown. Here we focus on a GH110 enzyme (PdGH110B) from the carrageenolytic marine bacterium Pseudoalteromonas distincta U2A. We showed that the enzyme was active on Galα1–3Gal but not the blood group B antigen. X-ray crystal structures in complex with galactose and unhydrolyzed Galα1–3Gal revealed the parallel β-helix fold of the enzyme and the structural basis of its inverting catalytic mechanism. Moreover, an examination of the active site reveals likely adaptations that allow accommodation of fucose in blood group B active GH110 enzymes or, in the case of PdGH110, accommodation of the sulfate groups found on λ-carrageenan. Overall, this work provides insight into the first member of a predominantly marine clade of GH110 enzymes while also illuminating the structural basis of α-1,3-galactoside processing by the family as a whole.

Injection of Aquafilling® for Breast Augmentation Causes Inflammatory Responses Independent of Visible Symptoms

Background A major concern related to modern surgery is to evaluate and address the complications associated with breast enlargement using Aquafilling® injection. This study aimed to assess the effect of Aquafilling® injection on immune response in such patients. Methods For four patients who consulted a surgeon after receiving Aquafilling® injection, medical history of the patients was taken; based on imaging examinations, Aquafilling® was removed. Samples were processed for histopathological and immunohistochemical examination. For detecting tissue antigens in histopathological samples, monoclonal antibodies against CD3 (lymphocytes T), CD 20 (lymphocytes B), and CD68 (macrophages) were used. By analyzing the images, the number of immune cells (lymphocytes T, lymphocytes B, and macrophages) and immunohistochemical reaction area were semiquantitatively evaluated. Results Different clinical features were observed in each patient after receiving Aquafilling® injection. In samples obtained from four patients, lymphocytes T (CD3), lymphocytes B (CD20), and macrophages (CD68) tissue expressions were observed. Statistically significant variations in the number of lymphocytes B (CD20) and macrophages (CD68), and differentiation of immunohistochemical reaction area for lymphocytes T (CD3) and lymphocytes B (CD20) were observed. Conclusions Inflammation is elevated in patients who received Aquafilling® injection. Medical imaging should be carried out in all such patients even if there are no visible symptoms. Removal of Aquafilling® can reduce the inflammation and risk of neoplastic progression in the patients. The influence of time elapsed since Aquafilling® injection and intensity of immune response requires further validation. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

A Postherpetic Isotopic Response Presenting as a Granuloma Annulare-Like Inflammatory Reaction

Isotopic response refers to the occurrence of a new, unrelated cutaneous disease occurring at the same location of a previous healed disease. The etiology of isotopic responses is still not completely understood. Theories have included that viral particles may lead to the development of the second disease, the destruction of nerve fibers by herpes zoster may lead to an indirect influence on the immune system, an alteration of microcirculation from inflammation that causes future insults to localize to the same site, and an exaggerated and atypical hypersensitivity reaction to tissue antigens, viral antigens, or immune complex deposition. A wide variety of disease processes have been reported as the second disease in an isotopic response.Here, we discuss a case of an isotopic response following herpes zoster in which the second disease involved a granuloma annulare (GA)-like inflammatory reaction that resolved and recurred. These findings support the theory that the skin affected by herpes zoster is affected in a way that makes it a focus for the manifestation of further skin diseases.