Antibodies to blood coagulation components are implicated in patients with multiple sclerosis

Hadjiagapiou, Maria S.; Krashias, George; Deeba, Elie; Christodoulou, Christina; Pantzaris, Marios; Lambrianides, Anastasia

doi:10.1016/j.msard.2022.103775

Cited by 7 publications

(18 citation statements)

References 38 publications

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“…Fifteen MS patients and 14 age- and gender-matched healthy participants ( p < 0.95 and p = 1.0, respectively) were recruited for the preclinical investigation of IgG antibodies against coagulation components. As previously reported [ 17 ], all patients tested positive for antibodies against coagulant serine proteases, whereas controls tested negative. Serum samples were also collected from 167 MS patients and 40 age- and gender-matched HCs for the purpose of screening and quantifying pro- and anti-inflammatory factors of interest in a large cohort of patients and comparing the results with those obtained from HC samples, as well as from our in vitro experiments.…”

Section: Methodssupporting

confidence: 72%

“…Following purification of the aforementioned IgG antibodies, the IgG activity was confirmed in all purified fractions by enzyme-linked immunosorbent assay (ELISA) ( Table 1 ), using a concentration of 100 μg/mL from each purified fraction tested. The initial ELISA protocols described in the methodology of our previous work were performed [ 17 ].…”

Section: Resultsmentioning

confidence: 99%

“…In our previous work, we achieved to show that an increased proportion of patients diagnosed with MS (43%) were positive for the presence of IgG antibodies against seven coagulation serine proteases, i.e., factor VIIa (FVIIa), thrombin, prothrombin, FXa, FXII, protein C, and plasmin, also demonstrating that such molecules can be correlated with advance disability status and progression of the disease [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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A Preclinical Investigation on the Role of IgG Antibodies against Coagulant Components in Multiple Sclerosis

et al. 2023

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The coagulation-inflammation interplay has recently been identified as a critical risk factor in the early onset of multiple sclerosis (MS), and antibodies against coagulation components have been recognized as contributing factors to thrombotic and inflammatory signaling pathways in diseases with overlapping symptoms to MS, paving the way for further research into their effects on MS pathology. The current study aimed to enlighten the role of IgG antibodies against coagulation components by performing a preclinical study, analyzing the astrocytic activation by purified IgG antibodies derived from 15 MS patients, and assessing their possible pro-inflammatory effects using a bead-based multiplexed immunoassay system. The results were compared with those obtained following astrocyte treatment with samples from 14 age- and gender-matched healthy donors, negative for IgG antibody presence. Serum samples collected from 167 MS patients and 40 age- and gender-matched controls were also analyzed for pro- and anti-inflammatory factors. According to our results, astrocytic activation in response to IgG treatment caused an upregulation of various pro-inflammatory factors, including cytokines, chemokines, and interleukins. Conversely, in serum samples from patients and controls, the pro-inflammatory factors did not differ significantly; medication may lower the levels in patients. Our findings suggest that antibodies may function as effectors in neuroinflammation and serve as targets for new treatments that eventually benefit novel therapeutic approaches.

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Section: Methodssupporting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Preclinical Investigation on the Role of IgG Antibodies against Coagulant Components in Multiple Sclerosis

et al. 2023

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“…In particular, male patients showed an EDSS median of 4.00 (interquartile range, IQR: 2.5–6.0) and MSSS median of 4.20 (IQR: 2.82–5.41), whereas female patients had an EDSS median of 3.0 (IQR: 2.5–4.75) and MSSS of 3.14 (IQR: 2.35–5.48). The patients were selected on the basis that they tested positive for at least one IgG antibody against coagulation components in our previous research work [ 31 ]. Table 1 shows the IgG antibodies that were analyzed, whereas detailed laboratory findings for each patient are provided in Supplementary Tables S1–S5 .…”

Section: Resultsmentioning

confidence: 99%

“…Although the etiology of MS is still under investigation, changes in the genetic makeup can affect the signaling pathways involved in the onset of MS. Previous studies have highlighted the importance of the interaction between coagulation components and inflammation [ 5 , 13 , 31 , 32 ], and, therefore, mutations in genes encoding procoagulant serine proteases or regulators of the coagulation cascade could be essential risk factors for MS.…”

Section: Discussionmentioning

confidence: 99%

Genetic Markers for Thrombophilia and Cardiovascular Disease Associated with Multiple Sclerosis

et al. 2022

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Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) with an unknown etiology, although genetic, epigenetic, and environmental factors are thought to play a role. Recently, coagulation components have been shown to provide immunomodulatory and pro-inflammatory effects in the CNS, leading to neuroinflammation and neurodegeneration. The current study aimed to determine whether patients with MS exhibited an overrepresentation of polymorphisms implicated in the coagulation and whether such polymorphisms are associated with advanced disability and disease progression. The cardiovascular disease (CVD) strip assay was applied to 48 MS patients and 25 controls to analyze 11 genetic polymorphisms associated with thrombosis and CVD. According to our results, FXIIIVal34Leu heterozygosity was less frequent (OR: 0.35 (95% CI: 0.12–0.99); p = 0.04), whereas PAI-1 5G/5G homozygosity was more frequent in MS (OR: 6.33 (95% CI: 1.32–30.24); p = 0.016). In addition, carriers of the HPA-1a/1b were likely to have advanced disability (OR: 1.47 (95% CI: 1.03–2.18); p = 0.03) and disease worsening (OR: 1.42 (95% CI: 1.05–2.01); p = 0.02). The results of a sex-based analysis revealed that male HPA-1a/1b carriers were associated with advanced disability (OR: 3.04 (95% CI: 1.22–19.54); p = 0.01), whereas female carriers had an increased likelihood of disease worsening (OR: 1.56 (95% CI: 1.04–2.61); p = 0.03). Our findings suggest that MS may be linked to thrombophilia-related polymorphisms, which warrants further investigation.

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Activity Sensing of Coagulation and Fibrinolytic Proteases

Sondag¹,

Verhoeven²,

Löwik³

et al. 2023

Chemistry A European J

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The blood coagulation cascade is a complex physiological process involving the action of multiple coupled enzymes, cofactors, and substrates, ultimately leading to clot formation. Serine proteases have a crucial role, and aberrations in their activity can lead to life-threatening bleeding disorders and thrombosis. This review summarizes the essential proteases involved in blood coagulation and fibrinolysis, the endogenous peptide sequences they recognize and hydrolyze, and synthetic peptide probes based on these sequences to measure their activity. The information in this review can contribute to developing novel anticoagulant therapies and specific substrates for point-of-care diagnosis of coagulation pathologies.

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Antibodies to blood coagulation components are implicated in patients with multiple sclerosis

Cited by 7 publications

References 38 publications

A Preclinical Investigation on the Role of IgG Antibodies against Coagulant Components in Multiple Sclerosis

A Preclinical Investigation on the Role of IgG Antibodies against Coagulant Components in Multiple Sclerosis

Genetic Markers for Thrombophilia and Cardiovascular Disease Associated with Multiple Sclerosis

Activity Sensing of Coagulation and Fibrinolytic Proteases

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