Monocyte chemoattractant protein 1 and chemokine receptor CCR2 productions in Guillain-Barré syndrome and experimental autoimmune neuritis.

Infiltration of activated lymphocytes and monocytes is a key phenomenon in the pathogenesis of Guillain-Barré syndrome (GBS) and experimental autoimmune neuritis (EAN). To investigate the role of chemokines, we determined the blood and nerve tissue expression of monocyte chemoattractant protein 1 (MCP-1), a major chemoattractant of monocytes and activated lymphocytes, and its receptor CCR2 in GBS and EAN. MCP-1 circulating levels (ng/ml) in GBS were increased at the time of progression, peaked at the time of plateau and normalized with recovery. MCP-1 circulating levels were the highest in the most disabled patients. The number of circulating CCR2 positive cells was lower in patients with GBS than in healthy subjects (p<0.004). In GBS, MCP-1 expression was observed in epineurial and endoneurial vessels, on infiltrating cells, Schwann cells and in the endoneurial extracellular matrix. Some CCR2 positive cells were observed in nerve biopsies of GBS patients. In EAN, a slight positivity for MCP-1 was observed in the sciatic nerve. There was no circulating CCR2 positive cells. However, at the time of plateau, a conspicuous infiltration of CCR2 positive cells was observed in the sciatic nerve that was no longer observed at the time of recovery. These results suggest that MCP-1 and CCR2 may participate to the recruitment of circulating mononuclear cells in nerve tissue in EAN and GBS.

Mast cell-associated Renaut bodies in the peroneal nerve of a dog with a history of mastocytosis.

Multiple Renaut bodies were identified by light microscopy in the biopsied common peroneal nerve of a dog with generalized neuropathy, hypothyroidism and a history of cutaneous mastocytosis. In addition, numerous granulated cells were associated with most of the Renaut bodies. Electron microscopic examination confirmed these to be mast cells, both central and peripheral to Renaut bodies, a phenomenon never previously reported. Endoneurial fibrosis, myelinated fiber loss, as well as evidence of axonal degeneration, demyelination and remyelination were observed. 'Vacuolation' of endoneurial fibroblasts was also present. The location of these Renaut bodies in the common peroneal nerve, and the absence of any documented or expected nerve compression, implicates other etiological factors. These observations are the first to report an association between mast cells and Renaut bodies. It is possible that mast cells, at least in this case, are involved in the formation of Renaut bodies.

Paraneoplastic demyelinating neuropathy, subacute sensory neuropathy, and anti-Hu antibodies: clinicopathological study of an autopsy case.

A patient with anti-Hu antibodies, small-cell lung carcinoma, and autopsy-proven subacute sensory neuropathy had early slowing of motor and sensory conduction velocities. In the peripheral nerves, chronic demyelinating and remyelinating lesions with axonal degeneration were associated with an inflammatory reaction consisting of CD8+ T cells and CD68+ macrophages. On immunohistochemical testing, the patient's serum did not react with normal nerve, suggesting that the Hu proteins were not the target of the inflammatory reaction in the nerve.

Reduction in peripheral nerve allograft antigenicity with warm and cold temperature preservation.

Lymphocyte migration into fresh and preserved peripheral nerve allografts was assessed to determine the effects of preservation time, preservation temperature, and graft harvest technique on the immunologic response to the peripheral nerve allograft. Peroneal nerve was harvested from either live or cadaveric (tissue) donors and stored as 1.5-cm segments at 5 degrees C or 37 degrees C for 1, 3, 5, or 7 days. Each of nine outbred ewes then received multiple segments of peroneal autograft, fresh allograft, and preserved nerve allograft implants. Lymphocyte migration was studied 7 days after implantation by intravenous injection of autologous 111In-labeled lymphocytes and quantified by gamma counter. Lymphocyte migration into fresh allografts (7212 +/- 1575) increased an average of 4.1 times over fresh autograft tissue (1758 +/- 421; p < 0.05). Short-term preservation (24 hours) at both temperatures enhanced lymphocyte migration into pretreated allograft tissue (12684 +/- 2575 at 5 degrees C, 8751 +/- 1577 at 37 degrees C) as compared with fresh allograft (7212 +/- 1575). Conversely, 7 days of pretreatment at both 5 degrees C (3586 +/- 1421) and 37 degrees C (1570 +/- 414) resulted in migration values not significantly different from autograft. No statistically significant difference was seen between grafts harvested from live (5710 +/- 1651) versus cadaveric (tissue) donors (4013 +/- 832) after 5 days of cold preservation.

Ganglioside GD1b is the target antigen for a biclonal IgM in a case of sensory-motor axonal polyneuropathy: involvement of N-acetylneuraminic acid in the epitope.

We report on a 54-year-old man with a sensory-motor polyneuropathy associated with a biclonal IgM-kappa gammopathy, which reacted with the ganglioside GD1b. Examination of nerve biopsy specimens showed some reduction in the density of myelinated fibers and axonal degeneration with a loss of large fibers and a relative increase in the density of small fibers. Immunodetection on thin-layer chromatography of the glycolipid antigens showed strong reactivity of the patient's serum IgM-kappa with GD1b ganglioside and weak binding to GD1a. biclonal IgM antibodies did not react with GM1, asialo-GM1, GT1b, GD2, or GD3. Indirect immunofluorescence staining showed binding of IgM-kappa mainly in a crescent-like pattern on the internal side of myelin sheaths, which could correspond either to an enlarged periaxonal (adaxonal) space or to the internal mesaxon or to both. The immunostaining was abolished after absorption of the serum with GD1b.

Nerve graft immunogenicity as a factor determining axonal regeneration in the rat.

Acellular basal lamina grafts have recently been reported to support axonal regeneration and have been used in peripheral nerve repair. The present study was designed to determine the immunogenicity of such basal lamina allografts (grafts that are genetically different) and their potential as bridging material for nerve gap repair. Inbred strains of Fischer and Buffalo rats with known histocompatibility differences were used. Acellular grafts were prepared by repeated freezing and thawing nerve tissue predegenerated in situ for 6 weeks. Non-frozen predegenerated nerves were used as cellular grafts for comparison. Fischer rats were used as hosts and received cellular or acellular grafts obtained from Fischer (isograft, genetically identical) or Buffalo (allograft) donors. The grafts were evaluated morphologically at 1, 2, 4, and 12 weeks after transplantation. The cellular isografts supported axonal regeneration best. The cellular allografts were invariably rejected and were unsuccessful or only partially successful in supporting regeneration. In contrast, acellular allografts, in spite of their mild immunogenicity were successful in supporting regeneration, as were the acellular isografts. The rate of host axonal regeneration and recovery of target muscle was reduced in acellular allografts and isografts as compared to cellular isografts. It is concluded that acellular allografts are suitable for supporting axonal regeneration and may be used to bridge gaps in injured peripheral nerves.

Relationship of tissue deposits of cryoglobulin to clinical features of mixed cryoglobulinemia.

Two patients with type 2 mixed cryoglobulinemia had tissue deposits of serum cryoproteins. Patient 1, a 72-year-old man, had purpura and glomerulonephritis. The serum cryoglobulin consisted of monoclonal IgM kappa and polyclonal IgG. Renal biopsy revealed diffuse proliferative glomerulonephritis with abundant IgG, IgM, kappa light chain, and complement in glomerular capillary walls. These immunoglobulins, but no complement, were also present in histologically normal cutaneous blood vessels. Ultrastructurally, cutaneous vascular deposits were identical to the renal deposits and to the crystalline mixed IgM-IgG serum cryoprecipitates and renal deposits previously described. Patient 2 was a 68-year-old man with sensorimotor peripheral polyneuropathy and purpura. His serum cryoglobulin consisted of monoclonal IgA lambda and polyclonal IgG. Sural nerve and skin biopsies revealed vasculitis involving small arteries and arterioles. Immunoglobulin A and complement were present in perineurial arteriolar walls of the sural nerve. Cryoprecipitates in both cases had strong rheumatoid factor activity. These findings support the view that in type 2 cryoglobulinemia tissue deposits consist of cryoprotein immune complexes. The presence of these deposits in histologically normal blood vessels in patient 1 suggests that deposition of cryoproteins precedes and may initiate tissue damage.