Unexpected Inflammation in the Sympathetic Ganglia in Thromboangiitis Obliterans

Farzadnia, Mehdi; Ravari, Hassan; Masoudian, Mitra; Valizadeh, Narges; Fazeli, Bahare

doi:10.1055/s-0037-1604410

Cited by 5 publications

(6 citation statements)

References 21 publications

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“…Recently, we discovered an infiltration of neutrophils and cytotoxic T lymphocytes in the SG of TAO patients [9]. In the current study, we wanted to discover if the infiltration of inflammatory cells in the SG of the patients was due to the presence of a pathogen inside the SG tissue or whether there was a reactive inflammation due to irritation of the peripheral nerves in ischaemic tissue or neural cell injuries in SG.…”

Section: Discussionmentioning

confidence: 95%

“…Moreover, mtDNA damage, the reactive oxidative stress that is induced by cigarette smoking, enhances the release of mtDNA into the cytoplasm and, consequently, induces the expression of HMGB1 to make an HMGB1-mtDNA complex that activates cytosolic TLR9 [27]. Following TLR9 activation, interleukin 8 (IL-8), a neutrophil chemoattractant, is released, which may explain the neutrophil infiltration in the SG of the patients [9, 25].…”

Section: Discussionmentioning

confidence: 99%

“…According to our recent study, the infiltration of cytotoxic T lymphocytes and neutrophils in the sympathetic ganglia (SG) of TAO patients has been reported [9]. However, it is not yet known whether the inflammation in the SG is due to the presence of a pathogen and pathogen-associated molecular patterns (PAMPs) or if there is a sterile inflammation because of the presence of damage-associated molecular patterns (DAMPs).…”

Section: Introductionmentioning

confidence: 99%

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Unexpected inflammation in the sympathetic ganglia in thromboangiitis obliterans: more likely sterile or infectious induced inflammation?

et al. 2019

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Introduction The aim of this study was to determine if the inflammation of the sympathetic ganglia (SG) in thromboangiitis obliterans (TAO) is induced by an infectious pathogen inside or if it is a reactive sterile inflammation. Methods For the purpose of this study, the gene expression of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), toll-like receptor 9 (TLR9), and the receptor for advanced glycation end-products (RAGE) were evaluated on the complementary DNA (cDNA) of the SG tissues of 24 TAO patients and two controls with hyperhidrosis by real-time polymerase chain reaction (PCR) and analysed by the Pfaffl method. Results The gene expression of HMGB1 and TLR9 increased by about 25- and 2-fold changes in the SG of the TAO patients, respectively. However, there was no change in the gene expression of TLR4 or RAGE. Conclusion It appears that the inflammation in the SG of TAO patients is more likely a sterile inflammation, and its trigger may be mitochondrial DNA (mtDNA). Cadmium in cigarettes could be responsible for the induction of mtDNA release to the cell cytoplasm. In addition, the high expression of HMGB1 may play a role in the pathogenesis of TAO and may be responsible for both clinical manifestation of the disease and the imaging findings. Moreover, HMGB1 may be a target for treatment protocols for TAO. Further studies are highly recommended.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Unexpected inflammation in the sympathetic ganglia in thromboangiitis obliterans: more likely sterile or infectious induced inflammation?

et al. 2019

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“…Recently, inflammation and infiltration of neutrophils and lymphocytes in the sympathetic ganglia of BD patients who underwent sympathectomy as a pain management protocol were demonstrated 4. Sympathetic ganglia inflammation may explain the generalized vasoconstriction in BD patients and the early-stage neurological manifestation of BD, including cold sensation, numbness, and paraesthesia 4. However, it is not known if the pathological changes in the sympathetic ganglia are also responsible for the circadian rhythmic nature of the pain or its burning quality.…”

Section: Discussionmentioning

confidence: 99%

<p>Vaso-nervorumitis: responsible for pain in Buerger’s disease?</p>

Fazeli¹,

Farzadnia²,

Taheri³

2019

IMCRJ

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Buerger’s disease (BD) is an episodic, inflammatory, and occlusive peripheral vascular disease with unknown etiology, which can lead to tissue or limb loss. BD patients usually present neurological symptoms from the early stages of the disease including numbness, cold sensation, and allodynia as the disease progresses. Pain in the late stages of BD is very severe, almost resistant to opioid pain killers, and sometimes compels the patient to pursue major amputation. Therefore, pain management in BD patients is one of the most important and, at the same time, challenging issues since its main etiology is not well understood. Recently, a 39-year-old male smoker with a diagnosis of BD underwent a below-knee amputation in his left leg. Oddly, we found that the vasa-nervorum of the sural nerve had the pathological changes usually observed in BD, including inflammation and proliferation of endothelial cells. Notably, the inflammation was limited to the vasa-nervorum and did not extend to the nerve fascicles. Our findings could provide a clue to taking the approach of managing pain in BD as if it were vasculitis neuropathy; and the inflammation of the vasa-nervorum individually might be responsible for the pain characteristic of BD. In addition, our findings could indicate that BD is a systemic vasculitis of microcirculation and, hence, a different treatment approach for BD might be needed in addition to antithrombotic and vasodilator.

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“…None of them smoke. In addition, the age distribution of the five male control groups is 43.60 ± 3.51; the median (min-max) is 44 (38)(39)(40)(41)(42)(43)(44)(45)(46)(47) and the average age values between the patient and control groups were found to not be statistically significant (independent samples t-test).…”

Section: Clinical Specimensmentioning

confidence: 94%

Comparative Analysis of Transcriptome Profiles in Patients with Thromboangiitis Obliterans

Öztan,

Bozbuğa,

İşsever

et al. 2023

Genes

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Background: Thromboangiitis obliterans (TAO) causes vascular insufficiency due to chronic inflammation and abrupt thrombosis of the medium and small arteries of the extremities. In our study, we aimed to determine biomarkers for the diagnosis of TAO by evaluating 15 male TAO patients with Shinoya diagnostic criteria and 5 healthy controls who did not have TAO-related symptoms in their family histories. Methods: The Clariom D Affymetrix platform was used to conduct microarray analysis on total RNA extracted from whole blood. A total of 477 genes (FC ≤ 5 or >5) common to the fifteen patient and five control samples were selected using comparative microarray analysis; among them, 79 genes were upregulated and 398 genes were downregulated. Results: According to FC ≤ 10 or >10, in the same TAO patient and control group, 13 genes out of 28 were upregulated, whereas 15 genes were downregulated. The 11 key genes identified according to their mean log2FC values were PLP2, RPL27A, CCL4, FMNL1, EGR1, EIF4A1, RPL9, LAMP2, RNF149, EIF4G2, and DGKZ. The genes were ranked according to their relative expression as follows: FMNL1 > RNF149 > RPL27A > EIF4G2 > EIF4A1 > LAMP2 > EGR1 > PLP2 > DGKZ > RPL9 > CCL4. Using protein–protein interaction network analysis, RPL9, RPL27A, and RPL32 were found to be closely related to EIF4G2 and EIF4A1. The Reactome pathway found pathways linked to 28 genes. These pathways included the immune system, cellular responses to stress, cytokine signaling in the immune system, and signaling by ROBO receptors. Conclusions: By figuring out the protein expression levels of the genes that have been found to explain how TAO disease works at the molecular level, it will be possible to figure out how well these chosen transcripts can diagnose and predict the disease.

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Unexpected Inflammation in the Sympathetic Ganglia in Thromboangiitis Obliterans

Cited by 5 publications

References 21 publications

Unexpected inflammation in the sympathetic ganglia in thromboangiitis obliterans: more likely sterile or infectious induced inflammation?

Unexpected inflammation in the sympathetic ganglia in thromboangiitis obliterans: more likely sterile or infectious induced inflammation?

<p>Vaso-nervorumitis: responsible for pain in Buerger’s disease?</p>

Comparative Analysis of Transcriptome Profiles in Patients with Thromboangiitis Obliterans

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Unexpected Inflammation in the Sympathetic Ganglia in Thromboangiitis Obliterans

Cited by 5 publications

References 21 publications

Unexpected inflammation in the sympathetic ganglia in thromboangiitis obliterans: more likely sterile or infectious induced inflammation?

Unexpected inflammation in the sympathetic ganglia in thromboangiitis obliterans: more likely sterile or infectious induced inflammation?

<p>Vaso-nervorumitis: responsible for pain in Buerger&rsquo;s disease?</p>

Comparative Analysis of Transcriptome Profiles in Patients with Thromboangiitis Obliterans

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<p>Vaso-nervorumitis: responsible for pain in Buerger’s disease?</p>