Expression of antigen processing and presenting molecules by Schwann cells in inflammatory neuropathies

Schwann cells are the myelinating glia cells of the peripheral nervous system (PNS) and can become targets of an autoimmune response in inflammatory neuropathies like the Guillain‐Barré syndrome (GBS). Professional antigen presenting cells (APCs) are known to promote autoimmune responses in target tissues by presenting self‐antigens. Other cell types could participate in local autoimmune responses by acting as nonprofessional APCs. Using a combined approach of immunocytochemistry, immunohistochemistry, and flow cytometry analysis we demonstrate that human Schwann cells express the antigen processing and presenting machinery (APM) in vitro and in vivo. Moreover, cultured human Schwann cells increase the expression of proteasome subunit delta (Y), antigen peptide transporter TAP2, and HLA Class I and HLA Class II complexes in an inflammatory environment. In correlation with this observation, Schwann cells in sural nerve biopsies from GBS patients show increased expression of antigen processing and presenting molecules. Furthermore, cultured human Schwann cells can proteolytically digest fluorescently‐labeled nonmammalian antigen ovalbumin. Taken together, our data suggest antigen processing and presentation as a possible function of Schwann cells that may contribute to (auto)immune responses within peripheral nerves. © 2009 Wiley‐Liss, Inc.     

Mouse Schwann cells activate MHC class I and II restricted T-cell responses,but require external peptide processing for MHC class II presentation

Schwann cells are the myelinating glia cells of the peripheral nervous system (PNS). In inflammatory neuropathies like the Guillain-Barré syndrome (GBS) Schwann cells become target of an autoimmune response, but may also modulate local inflammation. Here, we tested the functional relevance of Schwann cell derived MHC expression in an in vitro coculture system. Mouse Schwann cells activated proliferation of ovalbumin specific CD8+ T cells when ovalbumin protein or MHC class I restricted ovalbumin peptide (Ova_257–264 SIINFEKL) was added and after transfection with an ovalbumin coding vector. Schwann cells activated proliferation of ovalbumin specific CD4+ T cells in the presence of MHC class II restricted ovalbumin peptide (Ova_323–339 ISQAVHAAHAEINEAGR). CD4+ T-cell proliferation was not activated by ovalbumin protein or transfection with an ovalbumin coding vector. This indicates that Schwann cells express functionally active MHC class I and II molecules. In this study, however, Schwann cells lacked the ability to process exogenous antigen or cross-present endogenous antigen into the MHC class II presentation pathway. Thus, antigen presentation may be a pathological function of Schwann cells exacerbating nerve damage in inflammatory neuropathies.     

Neurodegeneration in autoimmune demyelination: recent mechanistic insights reveal novel therapeutic targets

Multiple sclerosis (MS) is the most common chronic demyelinating disease of the central nervous system (CNS) and the major cause of neurological disability in young adults in Western countries. In spite of intensive research efforts, treatment options established to date do not sufficiently prevent the accumulation of tissue damage and clinical disability in patients with MS. We here describe recently identified molecules responsible for the inflammatory and the neurodegenerative processes in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), and review new treatment options targeting both aspects of this disease.     

Comparison of laser surface scanning and fiducial marker-based registration in frameless stereotaxy. Technical note

The authors compared the accuracy of laser surface scanning patient registration using the commercially available Fazer (Medtronic, Inc.) with the conventional registration procedure based on fiducial markers (FMs) in computer-assisted surgery. Four anatomical head specimens were prepared with 10 titanium microscrews placed at defined locations and scanned with a 16-slice spiral computed tomography unit. To compare the two registration methods, each method was applied five times for each cadaveric specimen; thus data were obtained from 40 registrations. Five microscrews (selected following a randomization protocol) were used for each FM-based registration; the other five FMs were selected for coordinate measurements by touching with a point measurement stylus. Coordinates of these points were also measured manually on the screen of the navigation computer. Coordinates were measured in the same manner after laser surface registration. The root mean square error as calculated by the navigation system ranged from 1.3 to 3.2 mm (mean 1.8 mm) with the Fazer and from 0.3 to 1.8 mm (mean 1.0 mm) with FM-based registration. The overall mean deviations (the arithmetic mean of the mean deviations of measurements on the four specimens) were 3.0 mm (standard deviation [SD] range 1.4-2.6 mm) with the Fazer and 1.4 mm (SD range 0.4-0.9 mm) with the FMs. The Fazer registration scans 300 surface points. Statistical tests showed the difference in the accuracy of these methods to be highly significant. In accordance with the findings of other groups, the authors concluded that the inclusion of a larger number of registration points might improve the accuracy of Fazer registration.     

Association of adrenal medullar and cortical nodular hyperplasia: a report of two cases with clinical and morpho-functional considerations

Arterial hypertension of adrenal etiology is mainly attributed to primary hyperaldosteronism. However, subtle expressions of hyperadrenergic or glucocorticoid excess can also generate arterial hypertension. The present report describes two hypertensive patients cataloged as resistant essential hypertensives, in whom adrenal masses were found incidentally, who highlight the need to recognize these tenuous clinical or laboratory presentations. Case 1 was a 50-yr-old female with hyperadrenergic hypertension associated to a left adrenal node, normal cortisol and aldosterone:renin ratio, marginally increased urinary normetanephrine, and a positive 131I MIBG radioisotope scan. Adrenalectomy normalized blood pressure and urinary metanephrines. Pathology showed a hyperplastic adrenal medulla associated to a multinodular cortical hyperplasia. Case 2 was a 62- yr-old female with progressive hypertension, a slight Cushing phenotype, non-suppressible hypercortisolism, normal urinary metanephrines, and bilateral adrenal nodes. Bilateral adrenalectomy and subsequent replacement normalized blood pressure and phenotypic stigmata. Pathology demonstrated bilateral cortical multinodular hyperplasia and medullary hyperplasia. The clinical study in both patients was negative for MEN. The apparently rare association of cortical and medullary lesions presented by both patients is probably overlooked in routine pathology exams, but should be meticulously searched since the crosstalk between the adrenal cortex and medulla may prompt dual abnormalities.