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Objectives: Describe the history of the use of the term "lupus" as a disease and to point out the inaccuracies of previous lupus historical articles and correct the historical record. Methods: An exhaustive review of Medieval and later texts regarding the use of the term "lupus" as it was used for the name of a disease as well as personal communications with Medieval experts who have studied this topic. Results: There are three possible first uses of "lupus" as a disease: an affidavit written in 963 AD by Eraclius (Bishop of Liège, Belgium), in a 12th century historical account of the Bishop of Liège, falsely ascribed to the 9th century Bishop Herbernus, or in an 1170 AD letter written by Pierre de Blois about the death of archbishop Stephan du Perche. The first use of "lupus" in a medical text was by Rolando da Parma in a 1230 AD surgical treatise. Lupus, Latin for wolf, was not used to describe lesions that looked like wolf bites. Instead, it was first used to describe potentially deadly skin lesions that devoured the affected person's skin and "internal matter." The first described lupus treatment was freshly killed chicken flesh applied to the lesions so they would "wolfishly" eat the chicken rather than the person's flesh. At least 25 modern historical articles, book chapters, and academic theses on the topic contain incorrect dates, story authorship ascriptions, reason for the use of "lupus" and other facts. There is no proof that Hippocrates described lupus. The Basilica of St Martin (Liege, Belgium), was originally built in the 10th century by Eraclius, Bishop of Liege, out of gratitude to St Martin for curing him of "lupus." Conclusions: The first use of the word "lupus" as a disease originated in either the 10th or 12th centuries. It described a deadly disease affecting the buttocks and legs that "wolfishly" devoured the person's flesh and "internal matter" as well as doctor-prescribed fresh chicken flesh placed on the lesions. Authors of medical history articles should evaluate original historical texts and not simply repeat what other modern articles have written. [ABSTRACT FROM AUTHOR]

The antidiabetic medication metformin has been proposed to be the first drug tested to target aging and extend healthspan in humans. While there is extensive epidemiological support for the health benefits of metformin in patient populations, it is not clear if these protective effects apply to those free of age-related disease. Our previous data in older adults without diabetes suggest a dichotomous change in insulin sensitivity and skeletal muscle mitochondrial adaptations after metformin treatment when co-prescribed with exercise. Those who entered the study as insulin-sensitive had no change to detrimental effects while those who were insulin-resistant had positive changes. The objective of this clinical trial is to determine if (a) antecedent metabolic health and (b) skeletal muscle mitochondrial remodeling and function mediate the positive or detrimental effects of metformin monotherapy, independent of exercise, on the metabolism and biology of aging. In a randomized, double-blind clinical trial, adults free of chronic disease (n = 148, 40–75 years old) are stratified as either insulin-sensitive or resistant based on homeostatic model assessment of insulin resistance (≤2.2 or ≥2.5) and take 1 500 mg/day of metformin or placebo for 12 weeks. Hyperinsulinemic-euglycemic clamps and skeletal muscle biopsies are performed before and after 12 weeks to assess primary outcomes of peripheral insulin sensitivity and mitochondrial remodeling and function. Findings from this trial will identify clinical characteristics and cellular mechanisms involved in modulating the effectiveness of metformin treatment to target aging that could inform larger Phase 3 clinical trials aimed at testing aging as a treatment indication for metformin. Clinical Trials Registration Number : NCT04264897. [ABSTRACT FROM AUTHOR]

Aims: Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR).Methods and Results: Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of α1AR and β1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and β1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade. The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity.Conclusion: These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the α1AR and β1AR responsiveness are important in the pathophysiology of postural tachycardia. [ABSTRACT FROM AUTHOR]

Objective: Sjögren's Disease (SjD) subjects have decreased lacrimal/salivary gland function. Studies have proposed that autoantibodies targeting G-protein-coupled muscarinic acetylcholine-type-3-receptor (M3R) are potential clinical markers for SjD. We hypothesized that rabbits/mice immunized with 4-hydroxy-2-nonenal (HNE)-modified/unmodified Ro60 will develop an autoimmunity, specifically a SjD phenotype, thus expressing increased levels of anti-M3R antibodies., Methods: We immunized two rabbits each with 10 mM HNE-modified Ro60/unmodified Ro60 antigen or Ro274-290/Ro413-428/Ro500-517 Ro60 peptides. Two rabbits each were immunized with either M3R second extracellular loop (ECL2) or M3R ECL3 peptide. Finally, five groups of BALB/c mice were immunized as follows-Group-I immunized with Ro60, Groups-II-IV immunized with Ro60 modified with 0.4 mM (low), 2 mM (medium), and 10 mM (high) HNE, respectively and Group-V-Freund's adjuvant. Serum antibodies to M3R ECL2/ECL3/Ro60/La or Sm were detected by ELISA. Functional assays were also performed., Results: Immunization with HNE-modified Ro60/unmodified Ro60 antigen or Ro274/Ro 413/Ro500 peptides induced a rapid intermolecular epitope spreading to M3R ECL2/ECL3, especially to M3R ECL3 in HNE-Ro immunized rabbits. These animals did not bind to scrambled M3R peptides. Ro60-immunized rabbit IgG inhibited M3R activity in a functional assay. Rabbits immunized with ECL2/ECL3 developed high reactivity to Ro60 but not against Sm/RNP. We found a differential antibody-induction against M3R ECL2 with Group-3 mice developing significant reactivity., Conclusion: Our data show induction of increasing anti-M3R antibodies in rabbits immunized with Ro60/HNE-Ro60 or Ro60 peptides and differential induction of these antibodies in mice immunized with Ro60 modified with increasing HNE. These findings suggest that M3R ECL2/ECL3 are involved in SjD autoimmunity progression., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

For >95 years, the Department of Veterans Affairs Office of Research and Development (ORD) has been improving the lives of Veterans and all Americans through health care discovery and innovation. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives and creativity to address complex health-related problems, which helps to foster scientific innovation, improve quality of research, and advance the likelihood that underserved populations participate in and benefit from clinical and health services research. In this study, we will discuss our experiences in developing future scientists through mentored research supplements supported by ORD., Competing Interests: No competing financial interests exist., (© Darius B. Dawson et al., 2023; Published by Mary Ann Liebert, Inc.)

Aims: Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR)., Methods and Results: Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of α1AR and β1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and β1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade. The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity., Conclusion: These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the α1AR and β1AR responsiveness are important in the pathophysiology of postural tachycardia., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Sjogren's syndrome is a common autoimmune disease that presents with sicca symptoms and extraglandular features. Sjogren's syndrome is presumably as common as RA; yet it is poorly understood, underdiagnosed and undertreated. From the usual identity as an autoimmune exocrinopathy to its most recent designate as an autoimmune epithelitis - the journey of SS is complex. We herein review some of the most important milestones that have shed light on different aspects of pathogenesis of this enigmatic disease. This includes role of salivary gland epithelial cells, and their interaction with cells of the innate and adaptive immune system. Non-immune factors acting in concert or in parallel with immune factors may also be important. The risk genes identified so far have only weak association, nevertheless advances in genetics have enhanced understanding of disease mechanisms. Role of epigenetic and environmental role factors is also being explored. SS has also some unique features such as congenital heart block and high incidence of lymphoma; disease mechanisms accounting for these manifestations are also reviewed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Premature atherosclerosis is observed in systemic lupus erythematosus (SLE). Oxidative modification of LDL is associated with atherosclerotic plaque formation., Objectives: We hypothesized that anti-oxidized LDL (oxLDL) and anti-phospholipid (APL) in SLE sera would segregate with specific antibody subsets, and that anti-oxLDL antibodies will linger in circulation over an extended period., Patients and Methods: Sixty-seven SLE and control subjects and two SLE subjects with sera collected longitudinally for 13 years were tested for anti-oxLDL and IgG/IgM/IgA APL antibodies., Results: Anti-oxLDL ELISA values above 57.48 Activity Units (AcU) (means of normals + 3 standard deviations) and anti-IgG/IgM/IgA APL above 10 phospholipid units (PU) were considered positive. Average anti-oxLDL was 67.7 ± 50.5 AcU in SLE compared to 23.9 ± 11.19 AcU in normals (P = 0.018). Ten out of ten subjects with anti-Ro60/anti-La/anti-Ro52 antibodies had highly significant (P < 0.0001) anti-oxLDL (127.29 ± 45.67 AcU) and IgG APL (18.66 ± 7.4 PU) (P < 0.02). Subjects with anti-RNP were positive for anti-oxLDL (P < 0.002), but subjects with anti-Ro60/anti-Ro52 and subjects negative for extractable nuclear antigen (ENA) antibody were not positive for anti-oxLDL. Anti-oxLDL/anti-IgG APL remained significantly elevated in two patients studied longitudinally. Interestingly, one developed anti-oxLDL/anti-APL antibodies several years before anti-Ro60 development., Conclusions: Presence of antibodies against Ro RNP and La, and RNP is highly associated with developing anti-oxLDL and APL antibodies in SLE. It will be clinically important to see if cardiovascular events occur in these SLE subsets having elevated anti-oxLDL and APL antibodies. Emergence of anti-oxLDL/IgG APL before anti-Ro60 over time in a patient indicates that these antibodies could not be cross-reactive in nature, at least in this particular patient.