ARTICLE | doi:10.20944/preprints202207.0380.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: SARS-CoV-2; COVID-19; autoantibodies; autoimmune endocrinopathies; long-COVID syndrome; molecular mimicry; thyroid gland; adrenals; pituitary; Langerhans’ islets
Online: 26 July 2022 (03:42:01 CEST)
Molecular mimicry between human and microbial/viral/parasite peptides is common and for a long time is associated with the etiology of autoimmune disorders provoked by exogenous pathogens. Increasing evidence accumulated from the past years suggests a strong correlation between the SARS-CoV-2 infection and autoimmunity. The article analyzes the immunogenic potential of the peptides shared between SARS-CoV-2 spike glycoprotein (S-protein and antigens of human endocrinocytes involved in most common autoimmune endocrinopathies. Totally the study revealed 14 pentapeptides shared by S-protein of SARS-CoV-2 and autoantigens of thyroid, pituitary, adrenal cortex and Langerhans’ islets beta-cells, 12 of them belong to immunoreactive epitopes of SARS-CoV-2. The discussion of the data links the results with clinical correlates of COVID-associated autoimmune endocrinopathies. Most common of them is an autoimmune thyroid disease, so the majority of shared pentapeptides belong to marker autoantigens of this disease. Most important in pathogenesis of severe COVID-19, according authors’ opinion, can be autoimmunity against adrenals, because their adequate response prevents from excessive systemic action of inflammatory mediators which cause cytokine storm and hemodynamic shock. The criticism of antigen mimicry concept is given with a statement that peptide sharing is not a guarantee, but just a prerequisite of autoimmunity excess provocation. The last event occurs in carriers of certain HLA haplotypes and in case when shared peptide is used in antigen processing only [1 figure, 5 tables, bibliography 38 references].
ARTICLE | doi:10.20944/preprints202209.0289.v1
Subject: Medicine & Pharmacology, Other Keywords: chronic fatigue syndrome; post-COVID syndrome; postural orthostatic tachycardia; microcirculation; immune system
Online: 20 September 2022 (03:37:00 CEST)
A Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology under growing interest now in view of the increasingly recognized post-COVID syndrome as a new entity with similar clinical presentation. We performed the first cross-sectional study of ME/CFS in community population in Russia and then described and compared some clinical and pathophysiological characteristics of ME/CFS and post-COVID syndrome as neuroimmune disorders. Of the cohort of 76 individuals who suggested themselves suffering from ME/CFS 56 subsequently were confirmed as having CFS/ME according to ≥1 of the 4 most commonly used case definition. Of the cohort of 14 individuals with post-COVID-19 syndrome 14 met diagnostic criteria for ME/CFS. The prevalence of clinically expressed and subclinical anxiety and depression in ME / CFS and post-COVID ME/CFS did not differ significantly from that in healthy individuals. Severity of anxiety / depressive symptoms did not correlate with the severity of fatigue neigther in ME / CFS nor in post-COVID ME/CFS, but the positive correlation was found between the severity of fatigue and 20 other symptoms of ME / CFS related to the domains of “post-exertional exhaustion”, “immune dysfunction”, “sleep disturbances”, "dysfunction of the autonomic nervous system", "neurological sensory / motor disorders" and "pain syndromes". Immunological abnormalities were identified in 12/12 patients with ME / CFS according to the results of laboratory testing. The prevalence of postural orthostatic tachycardia assessed by the active standing test was 37.5% in ME / CFS and 75.0% in post-COVID ME/CFS (the latter was higher than in healthy controls, p = 0.02) There was a more pronounced increase in heart rate starting from the 6th minute of the test in post-COVID ME/CFS compared with the control group. Assessment of the functional characteristics of microcirculation by laser doppler flowmetry revealed obvious and very similar changes in ME/CFS and post-COVID ME/CFS compared to the healthy controls. The identified pattern corresponded to the hyperemic form of microcirculation disorders, usually observed in acute inflammatory processes or in deficiency of systemic vasoconstriction influences.
REVIEW | doi:10.20944/preprints202110.0118.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: male infertility; varicocele; varicocelectomy; spermatozoa; sperm antigens; antisperm autoantibodies; ejaculate; orchitis; autoimmune thyroiditis
Online: 7 October 2021 (11:40:21 CEST)
According to global data, there is a male reproductive potential decrease. Pathogenesis of male infertility often is associated with autoimmunity towards sperm antigens essential for fertilization. Antisperm autoantibodies (ASAs) have immobilizing and cytotoxic properties, impairing spermatogenesis, causing sperm agglutination, altering spermatozoa motility and acrosomal reaction, thus preventing ovum fertilization. Infertility diagnosis requires mandatory check for the ASAs. The concept of blood-testis barrier currently is re-formulated with emphasis of informational paracrine and juxtacrine effects, rather than simple anatomical separation. Aetiology of male infertility includes both autoimmune and non-autoimmune diseases, but equally develops through autoimmune links of pathogenesis. Varicocele commonly leads to infertility due to testicular ischemic damage, venous stasis, local hyperthermia, and hypoandrogenism. However, varicocelectomy can alter blood-testis barrier facilitating ASAs production as well. There are contradictory data on the role of ASAs in pathogenesis of varicocele-related infertility. Infection and inflammation both promote ASAs production due to “danger concept” mechanisms and because of antigen mimicry. Systemic pro-autoimmune influences like hyperprolactinemia, hypoandrogenism and hypothyroidism also facilitate ASAs production. Diagnostic value of various ASAs was not yet clearly attributed, and their cut-levels not agreed neither in sera nor in ejaculate. The assessment of the autoimmunity role in pathogenesis of male infertility is ambiguous.
Subject: Medicine & Pharmacology, General Medical Research Keywords: autoimmune diseases; antinuclear antibodies; antinuclear factor; functional autoantibodies; natural autoantibodies; physiological autoimmunity
Online: 8 January 2021 (14:01:32 CET)
Incidence of autoimmune diseases increases. Antinuclear antibodies (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in health increased over last decades, especially among young people. ANA in health occur in low concentrations, with prevalence up to 50% in some populations, which demands a cutoff revision. The review deals with origin and probable physiological or compensatory function of ANA in health, according to the concept of immunological clearance, theory of autoimmune regulation of cell functions and the concept of functional autoantibodies. Considering ANA titers ≤1:320 as a serological marker of autoimmune diseases seems inappropriate. The role of anti-DFS70/LEDGFp75 autoantibodies is highlighted as possible anti-risk biomarker for autoimmune rheumatic disorders. ANA prevalence in health is different in various regions due to several underlying causes discussed in the review, all influencing in additive combinations according to the concept of the mosaic of autoimmunity. Not only titer, but the HEp-2 IFA staining patterns, like AC-2, is also important. Accepting autoantibodies as a kind of bioregulators, not only upper, but also lower borders of their normal range should be determined. Not only their excess, but also lack of them or “autoimmunodeficiency” could be a reason of disorders.