Travel-Related Diagnoses Among U.S. Nonmigrant Travelers...
New Study Suggests KLF2 May Play A Role In Neutrophil Regulation And The Development Of Systemic Lupus Erythematosus
Neutropenia, a condition characterized by low neutrophil levels, is common in individuals with systemic lupus erythematosus (SLE) and can lead to severe infections. A new study investigates the role of Krüppel-like factor 2 (KLF2, a protein coding gene involved in a variety of regulatory pathways and plays a role in controlling inflammation) in regulating neutrophil apoptosis (cell death) and its connection to disease activity in people with SLE.
The study included 155 participants: 68 with SLE, 57 disease controls (29 with rheumatoid arthritis; 26 with Sjorgen's Syndrome), and 30 healthy controls. Researchers collected blood samples from each study participant, separated neutrophils, , and analyzed their rates of apoptosis.. They found that people with SLE had blood neutrophil counts that were significantly reduced, which was inversely linked to the SLE disease severity. The findings suggest that KLF2 in neutrophils may be closely related to the development and progression of SLE. The correlation between KLF2 and neutrophil apoptosis suggests that the decline of KLF2 levels may lead to neutropenia in people with SLE.
This is the first study to show that KLF2 can regulate the apoptosis of neutrophils. Further research is needed to provide insights into the detailed mechanisms leading to the occurrence and development of SLE. Additionally, this study highlights the potential of KLF2 in autoimmunity and as a therapeutic target. Learn more about lupus and inflammation.
Cutaneous Lupus Erythematosus Associated With Cardiovascular Disease
January 13, 2025
2 min read
Add topic to email alerts
Receive an email when new articles are posted on
Please provide your email address to receive an email when new articles are posted on . Subscribe We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.Com.Back to Healio
Patients with cutaneous lupus erythematosus may be at an increased risk for atherosclerotic cardiovascular disease, even more than those with psoriasis, according to a study.
"In dermatology, there is an emerging trend of evaluating comorbid disease with various dermatologic diseases," Henry W. Chen, MD, a dermatology resident at the University of Texas Southwestern Medical Center, told Healio. "This has been shown pretty well in psoriasis with an association of atherosclerotic disease (ASCVD). So, in this study, we sought to elucidate a potential association with ASCVD and cutaneous lupus erythematosus (CLE)."
The retrospective, matched, longitudinal, cohort study included 8,138 patients with strictly CLE and, for comparison, 24,675 patients with systemic lupus erythematosus (SLE), 192,577 with psoriasis and 81,380 controls.
Results showed that, compared with matched controls, patients with CLE were 1.72 (95% CI, 1.45-2.02) times more likely to have ASCVD, including myocardial infarctions, cerebrovascular accidents and coronary artery disease. Expectedly, the odds of ASCVD were lower among patients with CLE compared with SLE (OR = 2.41; 95% CI, 2.14-2.7), but interestingly they were higher compared with patients with psoriasis (OR = 1.03; 95% CI, 0.95-1.11).
"We didn't see a lot of association with cardiovascular disease within the psoriasis cohort compared with controls that were matched against CLE patients," Chen explained. "But one of the thoughts with that was that this study was designed to be matched to the CLE patients, so it's possible some of the study design did not show a signal in psoriasis patients as our primary interest was CLE patients."
After a median 3-year follow-up period, incidence rates of ASCVD per 1,000 person-years were highest in the SLE cohort (24.8; 95% CI, 23.3-26.4). This was followed by patients with CLE (15.2; 95% CI, 13.1-17.7) and those with psoriasis (14; 95% CI, 13.5-14.4).
According to a multivariable Cox proportional regression model, patients with SLE were 2.23 (95% CI, 2.05-2.43) times more likely to experience new onset ASCVD, patients with CLE were 1.32 (95% CI, 1.13-1.55) times more likely and those with psoriasis were 1.06 (95% CI, 0.99-1.13) times more likely compared with controls.
According to Chen, this study builds upon prior work and helps lay the groundwork for understanding that there is an association between CLE and ASCVD. He encourages dermatologists to make sure that patients with CLE are plugged in with a primary care physician who is screening them for cardiovascular disease, diabetes and other comorbidities.
"Dermatologists have the opportunity to intervene early as the skin is often viewed as a window to systemic disease," Chen told Healio. "Thus, I believe this understanding is one way we can help our patients with CLE by ensuring they are receiving appropriate screenings and by advocating for institution of timely interventions."
Published by:
Sources/DisclosuresCollapse Disclosures: Chen reports no relevant financial disclosures. Please see the study for all other authors' relevant financial disclosures.Add topic to email alerts
Receive an email when new articles are posted on
Please provide your email address to receive an email when new articles are posted on . Subscribe We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.Com.Back to Healio
The History Of Lupus
The history of lupus can be divided into three periods: classical, neoclassical, and modern. This article concentrates on developments in the present century which have greatly expanded our knowledge about the pathophysiology, clinical-laboratory features, and treatment of this disorder.
Lupus in the classical period (1230-1856)The history of lupus during the classical period was reviewed by Smith and Cyr in 1988. Of note are the derivation of the term lupus and the clinical descriptions of the cutaneous lesions of lupus vulgaris, lupus profundus, discoid lupus, and the photosensitive nature of the malar or butterfly rash.
The word 'lupus' (Latin for 'wolf') is attributed to the thirteenth century physician Rogerius who used it to describe erosive facial lesions that were reminiscent of a wolf's bite. Classical descriptions of the various dermatologic features of lupus were made by Thomas Bateman, a student of the British dermatologist Robert William, in the early nineteenth century; Cazenave, a student of the French dermatologist Laurent Biett, in the mid-nineteenth century; and Moriz Kaposi (born Moriz Kohn), student and son-in-law of the Austrian dermatologist Ferdinand von Hebra, in the late nineteenth century.
The lesions now referred to as discoid lupus were described in 1833 by Cazenave under the term "erythema centrifugum," while the butterfly distribution of the facial rash was noted by von Hebra in 1846. The first published illustrations of lupus erythematosus were included in von Hebra's text, Atlas of Skin Diseases, published in 1856.
Lupus in the neoclassical period (1872- 1948)The Neoclassical era of the history of lupus began in 1872 when Kaposi first described the systemic nature of the disorder: "...Experience has shown that lupus erythematosus ... May be attended by altogether more severe pathological changes, and even dangerous constitutional symptoms may be intimately associated with the process in question, and that death may result from conditions which must be considered to arise from the local malady."
Kaposi proposed that there were two types of lupus erythematosus; the discoid form and a disseminated (systemic) form.
Furthermore, he enumerated various signs and symptoms which characterized the systemic form, including:
The existence of a systemic form of lupus was firmly established in 1904 by the work of Osler in Baltimore and Jadassohn in Vienna. Over the next thirty years, pathologic studies documented the existence of nonbacterial verrucous endocarditis (Libman-Sacks disease) and wire-loop lesions in individuals with glomerulonephritis; such observations at the autopsy table led to the construct of collagen disease proposed by Kemperer and colleagues in 1941. This terminology, 'collagen vascular disease,' persists in usage more than seventy years after its introduction.
Lupus in the modern era (1948-present)The sentinel event which heralded the modern era was the discovery of the LE cell by Hargraves and colleagues in 1948. The investigators observed these cells in the bone marrow of individuals with acute disseminated lupus erythematosus and postulated that the cell "...Is the result of...Phagocytosis of free nuclear material with a resulting round vacuole containing this partially digested and lysed nuclear material...".
This discovery ushered in the present era of the application of immunology to the study of lupus erythematosus; it also allowed the diagnosis of individuals with much milder forms of the disease. This possibility, coupled with the discovery of cortisone as a treatment, changed the natural history of lupus as it was known prior to that time.
Two other immunologic markers were recognized in the 1950s as being associated with lupus: the biologic false-positive test for syphilis and the immunofluorescent test for antinuclear antibodies. Moore, working in Baltimore, demonstrated that systemic lupus developed in 7 percent of 148 individuals with chronic false-positive tests for syphilis and that a further 30 percent had symptoms consistent with collagen disease.
Friou applied the technique of indirect immunofluorescence to demonstrate the presence of antinuclear antibodies in the blood of individuals with systemic lupus. Subsequently, there was the recognition of antibodies to deoxyribonucleic acid (DNA) and the description of antibodies to extractable nuclear antigens (nuclear ribonucleoprotein [nRNP], Sm, Ro, La), and anticardiolipin antibodies; these autoantibodies are useful in describing clinical subsets and understanding the etiopathogenesis of lupus.
First animal model developedTwo other major advances in the modern era have been the development of animal models of lupus and the recognition of the role of genetic predisposition to the development of lupus. The first animal model of systemic lupus was the F1 hybrid New Zealand Black/New Zealand White mouse.
This murine (mouse) model has provided many insights into the immunopathogenesis of autoantibody formation, mechanisms of immunologic tolerance, the development of glomerulonephritis, the role of sex hormones in modulating the course of disease, and evaluation of treatments including recently developed biologic agents such as anti-CD4, among others.
Other animal models that have been used to study systemic lupus include the BXSB and MRL/lpr mice, and the naturally occurring syndrome of lupus in dogs.
Genetic component recognizedThe familial occurrence of systemic lupus was first noted by Leonhardt in 1954 and later studies by Arnett and Shulman at Johns Hopkins. Subsequently, familial aggregation of lupus, the concordance of lupus in monozygotic twin pairs, and the association of genetic markers with lupus have been described over the past twenty years.
Molecular biology techniques have been applied to the study of human lymphocyte antigen (HLA) Class II genes to determine specific amino acid sequences in these cell surface molecules that are involved in antigen presentation to T-helper cells in individuals with lupus. These studies have resulted in the identification of genetic-serologic subsets of systemic lupus that complement the clinico-serologic subsets noted earlier.
It is hoped by investigators working in this field that these studies will lead to the identification of etiologic factors (e.G., viral antigens/proteins) in lupus.
Over the last decade or so, we have witnessed significant advances in the understanding of the genetic basis of lupus, and of the immunological derangements which lead to the clinical manifestations of the disease.
Advances have been made in the assessment of the impact of the disease in general, and in minority population groups, in particular and efforts are being made towards defining lupus biomarkers which may help both to predict disease outcome and to guide treatments.
Lupus therapies then and nowFinally, no discussion of the history of lupus is complete without a review of the development of therapy. Payne, in 1894, first reported the usefulness of quinine in the treatment of lupus. Four years later, the use of salicylates in conjunction with quinine was also noted to be of benefit.
Cortisone/corticosteroids were introduced for the treatment of lupus in the middle part of the 20th century by Hench. Presently, corticosteroids are the primary therapy for almost all individuals with lupus.
Antimalarials, used in the past principally for lupus skin and joint involvement, are now recognized to prevent the occurrence of flares, the accumulation of damage, and the occurrence of early mortality.
Cytotoxic/immunosuppressive drugs are used for glomerulonephritis, systemic vasculitis, and other severe life-threatening manifestations of lupus. Newer biologic agents are now used, either off-label or after approval by regulatory agencies in the U.S., Europe, and other countries.
Other potential drug products are being investigated as new disease pathways are being discovered.
Looking forwardThe history of lupus, although dating back at least to the Middle Ages, has experienced an explosion in this century, especially during the modern era over the past 60 years. It is hoped that this growth of new knowledge will allow a better understanding of immunopathogenesis of the disease and the development of more effective treatments.
Comments
Post a Comment