Enolase and Arrestin are Novel Nonmyelin Autoantigens in Multiple Sclerosis

Forooghian, Farzin; Cheung, Roy K.; Smith, W. Clay; O’Connor, Paul; Dosch, Hans‐Michael

doi:10.1007/s10875-007-9091-1

Cited by 42 publications

(39 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, T cell responses against neuronal antigens have been demonstrated in MS patients and EAE- affected animals [8][9][10], and T cell-mediated EAE symptoms can be induced by immunization with neuronal antigens [11,13,14]. Despite this, we did not detect T cell proliferation against NF-L in CLN from EAE mice immunized with MOG or MOG [8][9][10][11][12][13][14][15][16][17][18][19][20][21] . The lack of T cell proliferation we consistently found might be due to the absence of intermolecular spreading or to the fact that the draining antigens may act immunosuppressively on proliferation within the draining lymph nodes.…”

Section: Discussioncontrasting

confidence: 66%

“…EAE was induced by immunization with spinal cord homogenate or myelin oligodendrocyte glycoprotein (MOG) [8][9][10][11][12][13][14][15][16][17][18][19][20][21] in CFA as described [27,28]. Deep and superficial CLN were also isolated from CCR7-deficient (n=4) and wild-type mice (n=4) [29] with chronic EAE, obtained from stock bred at the animal facility of the Max Delbrück Center for Molecular Medicine (Berlin, Germany).…”

Section: Eae Tissuesmentioning

confidence: 99%

“…A single cell suspension was obtained by passing the lymph nodes through a 70-μm gauze. Lymph node cells, 2×10 5 , were seeded into 96-well round-bottomed plates (Nunc) and stimulated with the indicated concentrations of MOG [8][9][10][11][12][13][14][15][16][17][18][19][20][21] , MOG (both from Advanced Biotechnology Center, Imperial College London), recombinant mouse NF-L (rmNF-L) [40], or ovalbumin (Worthington). After 4 days, T cell proliferation was determined by incorporation of [ 3 H]-thymidine for 18 h (Amersham Biosciences) as described [30].…”

Section: T Cell Proliferation Assaymentioning

confidence: 99%

“…Two experiments were using C57BL/6 mice in which EAE was induced by injection with MOG 35-55 (n=5-10 per experiment). One additional experiment was using Biozzi ABH mice (n=10) in which EAE was induced by injection with MOG [8][9][10][11][12][13][14][15][16][17][18][19][20][21] . Figure 5 shows a representative experiment, in which we observed dose-dependent T cell proliferation against the immunizing peptide MOG No proliferation against the irrelevant control antigen OVA was seen.…”

Section: Neuronal Antigen-containing Cells Have An Apc Phenotypementioning

confidence: 99%

“…Indeed, MS patients have increased circulating antibody levels against the neuronal proteins neurofilament light (NF-L) and neurofilament heavy (NF-H) [4][5][6] in serum and against the medium subunit of neurofilament in cerebrospinal fluid (CSF) [7]. In addition, T cells from MS patients proliferate in response to the neuronal antigens synapsin and neuron-specific enolase (NSE) [8,9]. In mice, T-cell-mediated autoimmunity against neuronal antigens leads to central nervous system (CNS) inflammation and experimental autoimmune encephalomyelitis (EAE) symptoms [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

et al. 2008

View full text Add to dashboard Cite

Drainage of central nervous system (CNS) antigens to the brain-draining cervical lymph nodes (CLN) is likely crucial in the initiation and control of autoimmune responses during multiple sclerosis (MS). We demonstrate neuronal antigens within CLN of MS patients. In monkeys and mice with experimental autoimmune encephalomyelitis (EAE) and in mouse models with non-inflammatory CNS damage, the type and extent of CNS damage was associated with the frequencies of CNS antigens within the cervical lymph nodes. In addition, CNS antigens drained to the spinal-cord-draining lumbar lymph nodes. In human MS CLN, neuronal antigens were present in pro-inflammatory antigen-presenting cells (APC), whereas the majority of myelin-containing cells were anti-inflammatory. This may reflect a different origin of the cells or different drainage mechanisms. Indeed, neuronal antigen-containing cells in J Mol Med (2009) human CLN did not express the lymph node homing receptor CCR7, whereas myelin antigen-containing cells in situ and in vitro did. Nevertheless, CLN from EAE-affected CCR7-deficient mice contained equal amounts of myelin and neuronal antigens as wild-type mice. We conclude that the type and frequencies of CNS antigens within the CLN are determined by the type and extent of CNS damage. Furthermore, the presence of myelin and neuronal antigens in functionally distinct APC populations within MS CLN suggests that differential immune responses can be evoked.

show abstract

Section: Discussioncontrasting

confidence: 66%

Section: Eae Tissuesmentioning

confidence: 99%

Section: T Cell Proliferation Assaymentioning

confidence: 99%

Section: Neuronal Antigen-containing Cells Have An Apc Phenotypementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

et al. 2008

View full text Add to dashboard Cite

show abstract

Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis

Huizinga

Star

Kipp

et al. 2011

Glia

View full text Add to dashboard Cite

Neuroaxonal degeneration is a pathological hallmark of multiple sclerosis (MS) contributing to irreversible neurological disability. Pathological mechanisms leading to axonal damage include autoimmunity to neuronal antigens. In actively demyelinating lesions, myelin is phagocytosed by microglia and blood-borne macrophages, whereas the fate of degenerating or damaged axons is unclear. Phagocytosis is essential for clearing neuronal debris to allow repair and regeneration. However, phagocytosis may lead to antigen presentation and autoimmunity, as has been described for neuroaxonal antigens. Despite this notion, it is unknown whether phagocytosis of neuronal antigens occurs in MS. Here, we show using novel, well-characterized antibodies to axonal antigens, that axonal damage is associated with HLA-DR expressing microglia/macrophages engulfing axonal bulbs, indicative of axonal damage. Neuronal proteins were frequently observed inside HLA-DR 1 cells in areas of axonal damage. In vitro, phagocytosis of neurofilament light (NF-L), present in white and gray matter, was observed in human microglia. The number of NF-L or myelin basic protein (MBP) positive cells was quantified using the mouse macrophage cell line J774.2. Intracellular colocalization of NF-L with the lysosomal membrane protein LAMP1 was observed using confocal microscopy confirming that NF-L is taken up and degraded by the cell. In vivo, NF-L and MBP was observed in cerebrospinal fluid cells from patients with MS, suggesting neuronal debris is drained by this route after axonal damage. In summary, neuroaxonal debris is engulfed, phagocytosed, and degraded by HLA-DR 1 cells. Although uptake is essential for clearing neuronal debris, phagocytic cells could also play a role in augmenting autoimmunity to neuronal antigens. V

show abstract

Vitreous proteomic analysis of proliferative vitreoretinopathy

Liu

Cui

et al. 2008

Proteomics

View full text Add to dashboard Cite

Proliferative vitreoretinopathy (PVR) is the most common cause of anatomic failure in retinal detachment surgery. To understand the molecular mechanisms, vitreous proteomes of patients with PVR were investigated by two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry. Vitreous samples of moderate PVR (grade B), and severe PVR (grade C or D) were aspirated during pars plana vitrectomy before infusion. In the current study, 129, 97 and 137 proteins were identified in vitreous of normal control, moderate and severe PVR, respectively. In PVR vitreous samples, complement components, serine proteinase inhibitors, and extracellular proteins were up-regulated or appeared, while normal cytoskeleton and metabolism proteins were down-regulated or disappeared. It was noteworthy that the proteins involved in transcription and translation regulation increased in vitreous with PVR. Among 102 PVR-specific proteins, kininogen 1 was specifically detected in both vitreous and the corresponding serum. Therefore, it can be concluded that PVR is a complicated pathology process with great amount of proteins involved in metabolism dysfunction, immune reactions, and cytoskeleton remolding. Kininogen 1 may be a candidate biomarker of PVR. Further investigations of these special proteins will provide additional targets for treatment or prevention of ocular proliferative diseases.

show abstract

Enolase and Arrestin are Novel Nonmyelin Autoantigens in Multiple Sclerosis

Cited by 42 publications

References 75 publications

Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis

Vitreous proteomic analysis of proliferative vitreoretinopathy

Contact Info

Product

Resources

About