The anti-Hu syndrome: a clinical and immunological study of 7 cases.

The authors describe the clinical and biological data of seven patients with anti-Hu antibodies. Six of them displayed a small cell lung carcinoma (SCLC), but no cancer was detected in the 7th patient in spite of an extensive workup. The clinical heterogeneity of the anti-Hu syndrome is emphasized. The major symptoms were linked to a severe sensory neuropathy in three cases, to cerebellitis in two cases, to dysautonomia in one case, and to gastro-intestinal pseudo-obstruction in one case. One patient also displayed EMG abnormalities characteristic of the Lambert-Eaton myasthenic syndrome. Two patients developed opsoclonus or ocular flutter associated with severe confusion in the late stage of their disease. In four patients, the neurological signs and symptoms preceded the discovery of the SCLC, and in two cases the initial detection of anti-Hu antibodies prompted the successful search for this tumor. Immunopathological events injuring the peripheral and central nervous system are briefly discussed.

Serum and CSF levels of soluble interleukin-2 receptors in MS and other neurological diseases: a reappraisal.

Soluble interleukin-2 receptors (sIL-2-R) were determined longitudinally in sera from 59 patients with multiple sclerosis (MS), from 20 patients with Guillain-Barré syndrome (GBS) and from patients with other non-inflammatory disorders of the nervous system, as well as in 147 CSF samples collected for diagnostic purposes. Significantly increased serum levels of sIL2-R were observed early in the course of GBS and in progressive (relapsing or chronic) MS, but not in patients with clinically stable MS or with an acute relapse followed by complete remission. CSF levels were high in infections of the central nervous system and in meningeal carcinomatosis, as a result of an intrathecal production, but were normal in GBS and in most (94%) MS patients.

Anti-Purkinje cells antibodies in two cases of paraneoplastic cerebellar degeneration.

The serum and CSF of two women with a severe subacute pancerebellar syndrome contained high titers of antibodies directed against antigens present in the perikaryon of Purkinje cells. In Western blots performed on human Purkinje cells extracts these antibodies reacted with two groups of proteins the molecular weights of which were estimated to 34-38 and 62 kilodaltons (anti-Yo antibodies). Complementary investigations revealed a tubar adenocarcinoma in the first case, an ovarian carcinoma in the second. The tubar tumoral cells also contained the protein of the highest molecular weight. Compared to the serum, the CSF contained a higher proportion of anti-Yo antibodies per mg IgG, and a fraction of the latter was likely synthesized intrathecally. These antibodies may be involved in the almost total disappearance of the Purkinje cells, as observed at autopsy of both cases.

Herpes simplex virus type 2 meningitis without genital lesions: an immunoblot study.

Two sexually active female patients presented with acute meningitis. The CSF abnormalities were severe and persistent. In spite of the absence of genital lesions, serological studies revealed a primary infection by herpes simplex virus type 2. An immunoblot study revealed intrathecal synthesis of anti-herpes antibodies early in the course of the disease.

Peripheral blood B and T-lymphocyte populations in patients with multiple sclerosis. Relationship with clinical activity of the disease and chronic immunosuppressive treatment.

During a period of 30 months, we studied the proportions of B and T cells, and of T cell subpopulations, in 924 blood samples from 213 MS patients. The disease was clinically stable in 88 patients (271 samples), relapsing progressive in 50 (349 samples), slowly progressive in 71 (262 samples) and in acute, selfremitting relapses for 31 patients (42 samples). By comparison with controls, untreated MS patients displayed a slightly higher percentage of B-cells (p less than 0.05) and a striking decrease of the mean percentage of CD8 + cells (p less than 0.001). Within the MS group, patients with an active disease presented a more marked decrease of the number of CD8 + cells and an increase of the CD4/CD8 ratio (p less than 0.01). However, 13 out of the 88 clinically stable patients had persistently high CD4/CD8 ratios, whereas such a high ratio was observed only in 60% of samples collected during an acute relapse. Eighty patients with a progressive form of the disease were chronically treated by immunosuppressive drugs, usually cyclophosphamide (N = 69). This treatment induced within one year a marked decrease of the absolute number of B and CD4 + cells, and a return to normal values of the CD4/CD8 ratio.

Monitoring and tentative diagnosis of herpetic encephalitis by protein analysis of cerebrospinal fluid. Particular relevance of the assays of ferritin and S-100.

The cerebrospinal fluid (CSF) of 9 patients with herpetic encephalitis was analyzed by particle counting immunoassay of ferritin, S-100, immunoglobulins, anti-herpes antibodies and immune complexes and by electrophoresis for the detection of oligoclonal bands. The main conclusions are: first, the simultaneous increase of both ferritin and S-100 in the presence of symptoms of encephalitis suggests strongly the infection is herpetic; second, high and increasing levels of S-100, probably related to the extent of the necrotic process, indicate a poor prognosis. In addition, 8-14 days after onset, locally produced anti-herpes antibodies were detectable, the IgG index increased and oligoclonal bands became visible.

Assessment of damage to the central nervous system by determination of S-100 protein in the cerebrospinal fluid.

S-100 protein was determined by Particle Counting ImmunoAssay in the CSF of patients with various neurological disorders. With a limit of sensitivity of 2.5 micrograms/l this brain-specific protein was detected only in samples from patients with acute damage of the central nervous system, particularly in compression of the spinal cord by tumour, ischaemic disorders, subarachnoïd bleeding and haematoma, and viral or suspected viral infections. Our results support the assumption that S-100 is a reliable index of central nervous system damage and that changes in its concentration could have a prognostic value.

In vitro immunosuppressive effect of serum from orally immunized mice.

Mice were orally immunized by 4 daily intragastric (IG) intubations of 4 X 10(9) SHEEP RED BLOOD CELLS (SRBC). The serum of such mice (OS), taken two weeks after the first intubation, was compared to normal mouse serum for its suppressive effect on in vitro primary responses of normal spleen cells to SRBC. OS regularly depressed the in vitro response to less than 10% of the normal response. The suppressive effect was dose-dependent, antigen-specific and removable by absorption with SRBC. When cultures were stimulated with SRBC pre-exposed to OS, the response was also depressed. The suppression was less when the addition of OS was delayed. OS from BALB/c mice efficiently depressed in vitro responses of spleen cells from other strains. Spleen cells, taken 2 weeks after IG immunization, responded normally to in vitro challenge with SRBC. The suppressive factor had the molecular size of an IgG and could be removed by anti-Ig and anti-IgG1 but not by anti-alpha or anti-mu immunosorbents. Purified IgG1 was more suppressive than IgG2a and IgG2b despite a similar anti-SRBC antibody content.

Interactions between mouse immunoglobulins and staphylococcal protein A.

When mouse serum or ascites is applied on protein A-Sepharose columns and washed with enough phosphate-buffered saline, a second protein peak is often eluted with the same buffer after the first major peak of unbound proteins. This second peak is almost pure Ig G1. More IgG1 plus IgG2a, IgG2b and IgG3 are thereafter eluted with acid saline. 90% of the IgG1 whichhad been eluted with neutral buffer could be re-eluted at the same retarded position with the same buffer. When a gradient from 0 to 3 M sodium thiocyanate was started after the major peak of unbound proteins, all IgG1 was eluted before IgG2 and IgG3. These results suggest that IgG1 has a much lower affinity for protein A than IgG2 or IgG3 and that normal mouse serum IgG1 can be purified by such a simple procedure.