Biomarkers of non-infectious inflammatory CNS diseases in dogs: Where are we now? Part 2 — Steroid responsive meningitis-arteritis

Andersen-Ranberg, Emilie; Berendt, Mette; Gredal, Hanne

doi:10.1016/j.tvjl.2021.105692

Cited by 8 publications

(10 citation statements)

References 79 publications

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“…Levels of acute phase proteins such as C-reactive protein, serum amyloid A, haptoglobin ( 53 ), or neutrophil gelatinase-associated lipocalin ( 54 ) are elevated in the acute disease episode compared to non-inflammatory neurological diseases. Especially, CRP is used as a remission and therapy monitoring marker ( 55 ). Pathohistologically, the acute form is represented by a multifocal to generalized fibrinoid-necrotizing vasculitis with thrombosis and purulent leptomeningitis preferentially in the meninges of the cervical spinal cord ( 40 , 43 , 56 – 58 ).…”

Section: Introductionmentioning

confidence: 99%

Detection of Extracellular Traps in Canine Steroid-Responsive Meningitis-Arteritis

et al. 2022

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Extracellular traps (ETs) are DNA networks formed by immune cells to fight infectious diseases by catching and attacking pathogenic microorganisms. Uncontrolled ET formation or impaired ET clearance can cause tissue and organ damage. Steroid-responsive meningitis-arteritis (SRMA) represents an immune-mediated, presumably non-infectious, purulent leptomeningitis and fibrinoid-necrotizing arteritis and periarteritis of young-adult dogs. Chronic and recurrent cases of SRMA are characterized by lymphohistiocytic inflammatory cell infiltration in the meninges and perivascular tissue. This study aimed to identify extracellular traps in dogs with SRMA, a model for immune-mediated diseases in the central nervous system (CNS). Hematoxylin and eosin-stained samples of two young dogs with chronic, recurrent SRMA were examined by light microscopy for characteristic lesions and consecutive slices of affected tissues were stained for detection of ETs by immunofluorescence microscopy using antibodies against DNA–histone-1 complexes, myeloperoxidase, and citrullinated histone H3. Histology revealed purulent and lymphohistiocytic leptomeningitis (n = 2/2) with meningeal periarteritis (n = 2/2) and periadrenal located lymphohistiocytic periarteritis (n = 1). Extracellular DNA networks and inflammatory cell infiltrates of macrophages, neutrophil granulocytes, and lymphocytes were detected in the subarachnoid space of the leptomeninx (n = 2/2) and perivascularly in meningeal (n = 2/2) as well as periadrenal vessels (n = 1/1). In summary, extracellular DNA fibers and attached ET markers are detectable in affected perivascular and meningeal tissues of dogs suffering from SRMA. The proof of principle could be confirmed that ETs are present in canine, inflammatory, and non-infectious CNS diseases and possibly play a role in the pathogenesis of SRMA.

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Section: Introductionmentioning

confidence: 99%

Detection of Extracellular Traps in Canine Steroid-Responsive Meningitis-Arteritis

et al. 2022

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“…On the other hand, steroid-responsive meningo-arteritis (SRMA), which is the second most common presumed immune-mediated inflammatory CNS disease after MUO [ 1 ], is typically characterized by an inflammatory leukogram with left-shift neutrophilia, along with neurological symptoms. [ 28 ]. In human medicine, the cause of increased neutrophil counts in CNS autoimmune disease and their role in the pathophysiology of the development of CNS autoimmunity has yet to be clarified [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…APPs have been previously investigated as biomarkers of systemic inflammation in dogs with SRMA [ 28 ]. A significant increase in serum and CSF CRP concentrations and a decrease in the serum albumin concentration have been shown in dogs with SRMA [ 28 ]; however, APPs behavior in MUO has been investigated only in one previous study comparing CSF and serum D-dimer and CRP concentration between groups with various neurological diseases [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Predictive Value of Acute Phase Proteins for the Short-Term Outcome of Meningoencephalitis of Unknown Origin in Dogs

Cocchetto

Zoia

Aragão

et al. 2023

Animals

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Meningoencephalitis of unknown origin (MUO) is one of the most common inflammatory diseases of the central nervous system (CNS). The study evaluates the possible increase and the potential role of acute phase proteins (APPs) and other inflammatory serum parameters as biomarkers predicting the short-term outcome of dogs with meningoencephalitis of unknown origin (MUO). A retrospective cohort study was designed. The APP profile and other markers of systemic inflammation of forty-eight client-owned dogs with a new diagnosis of MUO were compared between 7-day survival and non-survival dogs diagnosed with MUO. Thirty-nine (81%) dogs were alive at the end of the 7-day follow-up period, while 9 (19%) dogs died or were euthanized because of MUO. None of the 11 markers of inflammation studied were different between the survived and non-survived dogs; for this reason, none of them could be used as a predictor of the short-term outcome based on the results of the present study. This confirms that even though MUO is often associated with a severe inflammatory status of the central nervous system (CNS), this condition is probably isolated exclusively to the CNS.

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“…Several groups have used immunohistochemistry to look at B and T-cells in GME lesions with differing results as to the predominant cell type ( 15 – 18 ). Other groups have looked at various cytokines and chemokines in brain tissue and CSF ( 19 ). Specifically, evaluation of mRNA and protein expression levels in brain tissue from a small number of cases revealed elevated IFNg in NME and elevated IL17 in GME ( 1 ).…”

Section: Discussionmentioning

confidence: 99%

Differential T-cell responses in dogs with meningoencephalomyelitis of unknown origin compared to healthy controls

Barber

2022

Front. Vet. Sci.

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Meningoencephalomyelitis of unknown origin (MUO) is a common disorder in dogs that results in mononuclear inflammation in the brain and/or spinal cord. MUO is presumed to be autoimmune but specific immunological aberrations have not been identified. This exploratory study aimed to evaluate T cell production of two cytokines commonly implicated in autoimmune disease, interferon-gamma (IFNg) and interleukin-17 (IL17). Peripheral blood mononuclear cells were obtained from 12 dogs with MUO and 10 healthy controls, stimulated to activate intracellular signaling pathways, and stained with a cluster of differentiation 4 (CD4), cluster of differentiation eight (CD8), IFNg, and IL17 antibodies prior to analysis by flow cytometry. Mean differences in absolute cell numbers are represented as MUO cases minus healthy controls, and 95% Cis are reported. Overall IFNg-producing lymphocytes (mean difference = 241.8 cells/ul, 95% CI = 65.6 to 418.1) and CD4+ IFNg-producing T-cells (mean difference = 188.4, 95% CI = 77.3 to 299.5) were fewer in MUO cases. Additionally, CD4+ IL17-producing T-cells were greater in MUO cases (mean difference −34.9, 95% CI = −50.54 to −19.17) and CD8+ IL17-producing T-cells were fewer in MUO cases (mean difference = 73.5, 95% CI = 6.8 to 140.1). These results support that immunological changes can be identified in peripheral blood cells of dogs with MUO and suggest that T-helper type 17 (Th17) cells may play a role in pathogenesis.

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Biomarkers of non-infectious inflammatory CNS diseases in dogs: Where are we now? Part 2 — Steroid responsive meningitis-arteritis

Cited by 8 publications

References 79 publications

Detection of Extracellular Traps in Canine Steroid-Responsive Meningitis-Arteritis

Detection of Extracellular Traps in Canine Steroid-Responsive Meningitis-Arteritis

Predictive Value of Acute Phase Proteins for the Short-Term Outcome of Meningoencephalitis of Unknown Origin in Dogs

Differential T-cell responses in dogs with meningoencephalomyelitis of unknown origin compared to healthy controls

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