CSF/serum matrix metallopeptidase‐9 ratio discriminates neuro Behçet from multiple sclerosis

Aldinucci, Alessandra; Bonechi, Elena; Biagioli, Tiziana; Repice, Anna Maria; D’Elios, Mario Milco; Emmi, Lorenzo; Emmi, Giacomo; Silvestri, Elena; Barilaro, Alessandro; Ballerini, Clara

doi:10.1002/acn3.538

Cited by 16 publications

(5 citation statements)

References 27 publications

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“…[203][204][205] In the progressive disease course, when other CSF variables may be normal, the IL-6 concentration is raised, 50 206 although less raised than in acute attacks. 207 In one study, CXCL10 concentrations were higher than in samples from controls and patients with multiple sclerosis, 206 but not in another, 208 and IL-10 concentrations were the same in one study but not another. 207 209 B cell activating factor concentrations are higher in the CSF in those with progressive neurological Behçet's syndrome than those with acute episodes.…”

Section: Cerebrospinal Fluidmentioning

confidence: 89%

Neurological involvement by Behçet’s syndrome: clinical features, diagnosis, treatment and outcome

Kidd

2023

Pract Neurol

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Neurological involvement in Behçet’s syndrome arises predominately through an inflammatory meningoencephalitis characterised by perivenular inflammation due to activation of Th-17 immunological pathways. The brainstem is involved in 50% of cases, the diencephalon and other areas of the brain in 30%, and the spinal cord in 10%. Movement disorders and epilepsy may occur. Psychiatric syndromes may arise with brain and brainstem involvement, and cognitive disorders relate to the brain disease, to circulating inflammatory factors, and to fatigue and despondency. Eighty per cent of cases begin with a relapsing disease course, of whom 70% have only one attack, and 30% have a progressive disease course either from onset or following an initially relapsing course. Venous thrombosis leading to intracranial hypertension and cerebral venous infarction is less common and caused by inflammation in affected veins and a circulating prothrombotic state. Arterial involvement is rare and relates to an arteritis affecting large-sized and medium-sized vessels within the brain leading to infarction, subarachnoid and parenchymal haemorrhage, aneurysm formation and arterial dissection. There is a newly recognised disorder of cerebral cortical hypoperfusion. Cranial neuropathy, peripheral neuropathy and myositis are rare. There has been significant progress in understanding the pathophysiology and treatment of the systemic disease, leading to improved outcomes, but there has been no randomised trial of treatment in the neurological disorder.

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Section: Cerebrospinal Fluidmentioning

confidence: 89%

Neurological involvement by Behçet’s syndrome: clinical features, diagnosis, treatment and outcome

Kidd

2023

Pract Neurol

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“…Although less sensitive, CXCL13 CSF concentration showed very high specificity (60.0% sensitivity and 93.3% specificity). Several studies have also explored CSF CXCL13 expression in MS patients showing higher levels than in healthy controls or in patients with other inflammatory neurological diseases [36,37]. Furthermore, CXCL10 levels were higher in both RMS and PMS compared to non-inflammatory controls and CXCL8 levels in PMS compared to both control groups.…”

Section: Discussionmentioning

confidence: 99%

CSF CXCL13 and Chitinase 3-like-1 Levels Predict Disease Course in Relapsing Multiple Sclerosis

et al. 2022

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Several biomarkers from multiple sclerosis (MS) patients’ biological fluids have been considered to support diagnosis, predict disease course, and evaluate treatment response. In this study, we assessed the CSF concentration of selected molecules implicated in the MS pathological process. To investigate the diagnostic and prognostic significance of CSF concentration of target candidate biomarkers in both relapsing (RMS, n = 107) and progressive (PMS, n = 18) MS patients and in other inflammatory (OIND, n = 10) and non-inflammatory (ONIND, n = 15) neurological disorders. We measured the CSF concentration of APRIL, BAFF, CHI3L1, CCL-2, CXCL-8, CXCL-10, CXCL-12, CXCL-13 through a Luminex Assay. MS patients were prospectively evaluated, and clinical and radiological activity were recorded. CHI3L1 and CXCL13 CSF levels were significantly higher in both MS groups compared to control groups, while CCL2, BAFF, and APRIL concentrations were lower in RMS patients compared to PMS and OIND. Considering RMS patients with a single demyelinating event, higher concentrations of CHI3L1, CXCL10, CXCL12, and CXCL13 were recorded in patients who converted to clinically defined MS(CDMS). RMS patients in the CXCL13 and CHI3L1 high concentration group had a significantly higher risk of relapse (HR 12.61 and 4.57), MRI activity (HR 7.04 and 2.46), and of any evidence of disease activity (HR 12.13 and 2.90) during follow-up. CSF CXCL13 and CHI3L1 levels represent very good prognostic biomarkers in RMS patients, and therefore can be helpful in the treatment choice. Higher CSF concentrations of neuro-inflammatory biomarkers were associated with a higher risk of conversion to CDMS in patients with a first clinical demyelinating event. Differential CSF BAFF and APRIL levels between RMS and PMS suggest a different modulation of B-cells pathways in the different phases of the disease.

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“…The same authors showed significant elevation of CSF IL-6 in patients with progressive NBD compared to patients with active BD without neurological manifestations [ 24 ]. Moreover, it was noted that CSF, but not serum samples of NBD patients with acute parenchymal NBD, displayed significantly increased IL-6 levels, as compared to other groups [ 40 ]. Wang, et al, showed that the IL-6 level, which was higher in CSF of NBD patients, dropped when the disease activity subsided [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Increased T-bet/GATA-3 and ROR-γt /Foxp3 Ratios in Cerebrospinal Fluid as Potential Criteria for Definite Neuro-Behçet’s Disease

Belghith

Maghrebi

Cherif

et al. 2022

JCM

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When the central nervous system (CNS) is the primary affected site in an initial attack of Behçet’s disease (BD), the differential diagnosis is particularly challenging. Some cases remain unclassified or qualified as probable neuro-Behçet’s disease (NBD). Several cytokines are involved in the immunopathogenesis of this disease; however, studies establishing the differential cytokine pattern between probable and definite NBD are scarce. Twenty-eight parenchymal NBD patients, diagnosed according to the International Consensus Recommendation (ICR) criteria and classified into definite (D-NBD; n = 17) and probable (P-NBD; n = 11), were sampled at their first neurological symptoms, and compared with healthy control subjects (n = 20). Oligoclonal bands (OCB) of IgG were detected by isoelectric focusing on agarose, and immunoblotting of matched serum and cerebrospinal fluid (CSF) sample pairs. T cell cytokines (INF-γ, IL-4, IL-17, and IL-10) and transcription factors related to Th1, Th2, Th17, and T regulatory populations (respectively T-bet, GATA-3, ROR-γt, and Foxp3) were studied by quantitative RT-PCR in peripheral blood mononuclear cells (PBMCs) and CSF cells. Inflammatory cytokines such as IL-6, TNF-α, and IL-1β were also analyzed. CSF OCB pattern 2 was present in only 1 out of 28 neuro-Behçet’s patients who belonged to the P-NBD group. Two D-NBD patients had OCB in CSF showing pattern 4. In the D-NBD CSF samples, IL-17 and IL-10 expressions were significantly elevated compared to P-NBD. Moreover, D-NBD patients had increased levels of T-bet/GATA-3 and ROR-γt/Foxp3 ratios compared to P-NBD. Furthermore, a significant increase of CSF IL-6 in D-NBD, compared to P-NBD and the controls, was found. In addition to the increased IL-6 level, the data obtained suggest the existence in D-NBD patients of a significantly disrupted balance between Th17 effector and T regulatory cells, as reflected by the enhanced ROR-γt/Foxp3 ratio. This could be considered as an additional criterion for definite neuro-Behçet’s disease.

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CSF/serum matrix metallopeptidase‐9 ratio discriminates neuro Behçet from multiple sclerosis

Cited by 16 publications

References 27 publications

Neurological involvement by Behçet’s syndrome: clinical features, diagnosis, treatment and outcome

Neurological involvement by Behçet’s syndrome: clinical features, diagnosis, treatment and outcome

CSF CXCL13 and Chitinase 3-like-1 Levels Predict Disease Course in Relapsing Multiple Sclerosis

Increased T-bet/GATA-3 and ROR-γt /Foxp3 Ratios in Cerebrospinal Fluid as Potential Criteria for Definite Neuro-Behçet’s Disease

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