Sural nerve T-cell receptor Vbeta gene utilization in chronic inflammatory demyelinating polyneuropathy and vasculitic neuropathy.

OBJECTIVE: To investigate the utilization of T-cell receptor (TCR) variable (V) regions in infiltrates of sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy. BACKGROUND: The presence of infiltrating T lymphocytes in sural nerve biopsies may suggest a T cell-mediated immune mechanism in the pathogenesis of CIDP and vasculitic neuropathy. PATIENTS AND METHODS: The utilization of TCR Vbeta regions in sural nerves of 13 patients with CIDP and five patients with vasculitic neuropathy was determined by immunohistochemistry, reverse-transcription PCR, and nucleotide sequence analysis. These techniques were also applied in four patients with chronic idiopathic axonal polyneuropathy (CIAP) who acted as noninflammatory controls, and in five autopsy controls. RESULTS: The TCR Vbeta utilization of infiltrating T cells in sural nerves of patients with CIDP, vasculitic neuropathy, and noninflammatory controls is heterogeneous. A dominant TCR Vbeta utilization was not found in any of the patients or controls. CONCLUSION: There is no evidence for the presence of clonally expanded T cells in sural nerves of patients with CIDP and vasculitic neuropathy.

Selective expansion and long-term culture of human Schwann cells from sural nerve biopsies.

Fragments of sural nerve biopsy specimens were cultured in the presence of the supernatant of lymphokine-activated killer cells, resulting in the selective outgrowth of cells with bipolar or tripolar morphology, reminiscent of that of Schwann cells. Immunofluorescent staining with antibodies to the S-100 protein, the low-affinity nerve growth factor receptor, and the surface Thy-1 antigen confirmed that these cultures contained more than 99% Schwann cells and no detectable fibroblasts. The mitotic activity of Schwann cells was measured by bromodeoxyuridine labeling, and was increased when the cells were grown in medium with lymphokine-activated killer cell supernatant compared with medium without this supernatant. In the presence of lymphokine-activated killer cell supernatant, Schwann cells could be maintained in continuous culture for a minimum of 8 months.

Treatment of multifocal motor neuropathy with high dose intravenous immunoglobulins: a double blind, placebo controlled study.

The effect of high dose intravenous immunoglobulin (IVIg) treatment was studied in six patients with multifocal motor neuropathy (MMN). All patients responded to treatment (0.4 g/kg for five consecutive days) in an open trial. The effect of IVIg treatment was confirmed for each patient in a single patient, double blind, placebo controlled trial. Four patients received two IVIg treatments and two placebo treatments, and two patients received one IVIg and one placebo treatment in a randomised order. Five out of six patients responded to IVIg but not to placebo. One patient responded to IVIg in the same manner as to placebo treatment. Thus IVIg treatment can lead to improvement of muscle strength in patients with MMN.

Increased frequencies of HPRT mutant T lymphocytes in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy: further evidence for a role of T cells in the etiopathogenesis of peripheral demyelinating diseases.

We have used the HPRT mutant clonal assay to determine the frequency of mutant T lymphocytes (FMC), as a measure of recent T cell stimulation, in the blood of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). We found that, compared to healthy controls, the FMC in patients with GBS (16) and CIDP (10) was significantly increased in the progressive phase of the neuropathy. FMC returned to normal values during recovery, suggesting a relationship between FMC and disease activity. No correlation was found between FMC values and motor deficit or severity of the neuropathy. The FMC of the GBS patients with a history of infection before onset of neurological symptoms or with insufficient respiration was not significantly different from the other GBS patients. Immunophenotypic analysis showed that the fraction of CD8+ HPRT mutant T cell clones was significantly increased in GBS patients (48%) compared to healthy controls (3%) or CIDP patients (4.5%). Our results are compatible with the notion that T cells are involved in the pathogenesis of demyelinating inflammatory neuropathies.