Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis

Graßhoff, Hanna; Fourlakis, Konstantinos; Comdühr, Sara; Riemekasten, Gabriela

doi:10.3390/biomedicines10092150

Cited by 10 publications

(26 citation statements)

References 222 publications

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“…Autoantibody profiles in SSc are predictive of disease course and organ involvement. 51 When patients were stratified according to autoantibodies there was a significant increase in copeptin concentration in anti-RNAP III-positive patients. This is in accordance with several observations showing that SSc patients with positive anti-RNAP III antibodies had more frequently rapidly progressive diffuse skin thickening and higher frequency of vascular involvement, such as scleroderma renal crisis, pulmonary hypertension and ischemic damage associated with RP.…”

Section: Discussionmentioning

confidence: 98%

Copeptin as a Biomarker of Microcirculation Alterations in Systemic Sclerosis

Maciejewska¹,

Stec²,

Zaremba³

et al. 2023

CCID

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Background Systemic sclerosis is a connective tissue disease characterized by vasculopathy and progressive fibrosis, leading to multiorgan dysfunction. Given the complex and not fully elucidated pathogenesis, biomarkers of rapid disease progression and therapeutic response are lacking. Copeptin, which reflects vasopressin activity in serum, is used in diagnosing or prognosing different cardiometabolic conditions. Objective The aim of study was to investigate the concentration of copeptin in patients with systemic sclerosis and correlate it with specific clinical symptoms. Patients and Methods Serum copeptin was measured in patients with systemic sclerosis (34 women and 3 men; mean age 57.6 years) and in healthy individuals (n=30) using commercially available ELISA kits. According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). According to the criteria of LeRoy our systemic sclerosis cohort consisted of 17 patients with limited cutaneous systemic sclerosis (45.9%) and 20 diffuse cutaneous systemic sclerosis patients (54.1%). The median duration of the disease was 10 [4–14] years. Results We found significantly higher copeptin concentration in patients with systemic sclerosis (4.21 pmol/L [3.04–5.42]) in comparison to control group (3.40 pmol/L [2.38–3.76], p<0.01). Copeptin significantly correlated with Raynaud’s condition score (r=0.801, p<0.05). Patients with “late” capillaroscopic patterns had higher copeptin concentrations (5.37 pmol/L [4.29–8.06]) than patients with “early” (2.43 pmol/L [2.25–3.20], p<0.05) and “active” patterns (3.93 pmol/L [2.92–5.16], p<0.05]). Copeptin was found to be significantly higher in SSc patients with DUs (5.71 pmol/L [IQR 4.85–8.06]) when compared to SSc patients without DUs (3.31 pmol/L, [2.28–4.30], p<0.05). Additionally, copeptin concentration had good diagnostic accuracy in discriminating between patients with and without digital ulcers (AUC=0.863). Alprostadil decreased copeptin concentration from 4.96 [4.02–6.01] to 3.86 pmol/L [3.17–4.63] (p<0.01) after 4–6 cycles of administration. Conclusion Our findings suggest that copeptin may be a promising biomarker of microcirculation alterations in systemic sclerosis.

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Section: Discussionmentioning

confidence: 98%

Copeptin as a Biomarker of Microcirculation Alterations in Systemic Sclerosis

Maciejewska¹,

Stec²,

Zaremba³

et al. 2023

CCID

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“…It is generally accepted that GPCR autoantibodies are produced against the extracellular regions of the receptor. Depending on the epitope to which they specifically bind, and on their type (monovalent, bivalent), autoantibodies are able to either stimulate or suppress the basal or agonist-stimulated activity of a recognized receptor and, thereby, be involved in the pathogenesis of various diseases [99, [235][236][237]. In this regard, it is interesting that in the case of CXCR3 and CXCR4, patterns of autoantibodies have been identified that are specific not only to extracellular regions, but also to their ICLs.…”

Section: Autoantibodies To Chemokine Receptors Cxcr3 and Cxcr4mentioning

confidence: 99%

“…Endogenous allosteric regulators of PAR1 are autoantibodies produced against its extracellular domains [237,[292][293][294]. A significant proportion of patients with systemic sclerosis have autoantibodies to extracellular regions of PAR1, which are able to activate the receptor, like thrombin, thus acting as allosteric agonists [293].…”

Section: Autoantibodies To Par1mentioning

confidence: 99%

Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands

Ao¹

2023

Preprint

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A separate group consists of compounds that are able to simultaneously interact with both orthosteric and allosteric sites, which are classified as bitopic GPCR ligands [74, 76-81]. They have two pharmacophores, one of which binds with high affinity to the orthosteric site, while the other, with lower affinity, binds to the allosteric site. If these sites are spatially separated in the receptor, then the pharmacophores in the bitopic ligand must be connected with a flexible linker, the length of which exactly corresponds to the distance between the orthosteric and allosteric sites. At the same time, it is important that the linker does not significantly affect the conformational rearrangements in the receptor caused by its activation by orthosteric and (or) allosteric agonists [74, 79].

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“…Data on the therapeutic potential of these procedures come from small studies and case reports, generally reporting favourable therapeutic effects on skin fibrosis, musculoskeletal symptoms, Raynaud's phenomenon, the healing of digital ulcers and organ manifestation. These techniques are reviewed in detail elsewhere [143].…”

Section: Mechanical Removal Of Autoantibodiesmentioning

confidence: 99%

Novel Therapeutic Strategies in the Treatment of Systemic Sclerosis

et al. 2023

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Systemic sclerosis is a connective tissue disease of unknown origin and with an unpredictable course, with both cutaneous and internal organ manifestations. Despite the enormous progress in rheumatology and clinical immunology, the background of this disease is largely unknown, and no specific therapy exists. The therapeutic approach aims to treat and preserve the function of internal organs, and this approach is commonly referred to as organ-based treatment. However, in modern times, data from other branches of medicine may offer insight into how to treat disease-related complications, making it possible to find new drugs to treat this disease. In this review, we present therapeutic options aiming to stop the progression of fibrotic processes, restore the aberrant immune response, stop improper signalling from proinflammatory cytokines, and halt the production of disease-related autoantibodies.

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Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis

Cited by 10 publications

References 222 publications

Copeptin as a Biomarker of Microcirculation Alterations in Systemic Sclerosis

Copeptin as a Biomarker of Microcirculation Alterations in Systemic Sclerosis

Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands

Novel Therapeutic Strategies in the Treatment of Systemic Sclerosis

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