Serum antibodies to heat shock protein 70 in sensorineural hearing loss.

OBJECTIVE: To identify the 68-kd target of antibody in serum samples from patients with idiopathic, progressive, bilateral sensorineural hearing loss. DESIGN: To purify target protein from renal extracts using gel filtration, ion-exchange chromatography, and polyacrylamide gel electrophoresis and to transfer to nitrocellulose membranes. The purified protein was digested with trypsin, and peptide fragments were separated by high-pressure liquid chromatography. RESULTS: One fraction obtained by high-performance liquid chromatography contained a peptide of 2776 molecular weight. The sequence of a stretch of 22 amino acids within this peptide was identical to that of amino acids 424 through 445 of heat shock protein 70 (HSP70). On Western blotting, monoclonal antibody directed against HSP70 (but capable of recognizing both constitutive HSP70 [HSC70] and stress-inducible HSP70) reacted with the purified 68-kd protein. We compared the reactivity of serum samples from six patients with idiopathic, progressive, bilateral sensorineural hearing loss, as well as monoclonal antibody to HSC70, and monoclonal antibody to HSP70 with renal extract. The pattern obtained suggested that patient antibodies are preferentially directed at HSP70. CONCLUSION: The target of antibody in serum samples from patients with idiopathic, progressive, bilateral sensorineural hearing loss is HSP70.

Serum antibodies against heat shock protein 70 in Menière's disease.

Menière's syndrome of fluctuating sensorineural hearing loss, episodic vertigo, and tinnitus is the clinical presentation resulting from several different pathologic processes. The present study was designed to probe for immunologic factors in Menière's disease. It has previously been shown that the presence of circulating antibodies against a 68-kD protein detected by Western blot immunoassay of serum from patients with idiopathic, progressive, bilateral sensorineural hearing loss (IPB SNHL) is highly correlated with both activity of disease and corticosteroid responsiveness of the hearing loss. The authors recently have identified the 68-kD protein as heat shock protein 70 (HSP70). This study presents a retrospective review of results of Western blot assays in 30 patients meeting strict AAO-HNS diagnostic criteria for Menière's disease. Overall, 47% of patients had anti-HSP70 antibodies. When broken down by clinical pattern, anti-HSP70 antibodies were present in 58.8% of bilateral Menière's disease, 37.5% of contralateral delayed endolymphatic hydrops, and 33.3% of unilateral Menière's disease with IPB SNHL in the second affected ear. Detection of antibodies to HSP may serve to identify a subset of patients with Menière's disease in whom immunologic factors have a pathogenic role.

Serum antibody to inner ear proteins in patients with progressive hearing loss. Correlation with disease activity and response to corticosteroid treatment.

OBJECTIVE: To test whether detection of serum antibody to a 68-kd inner ear protein distinguishes among different causes of sensorineural hearing loss, and identifies patients with active disease and those likely to respond to corticosteroid therapy. DESIGN: Serum samples were tested by Western blot using bovine inner ear extract as antigen, and results were correlated with patient information obtained by chart review. SETTING: Referral center. SUBJECTS OF STUDY: Serum samples were obtained from patients with idiopathic, progressive, bilateral sensorineural hearing loss (IPBSNHL) (n = 72) otosclerosis (n = 11), Cogan's syndrome (n = 8), patients with positive tests for antinuclear antibodies (n = 10), and normal controls (n = 53). MAIN OUTCOME MEASURE: Detection of serum antibody to a 68-kd inner ear protein. RESULTS: Serum from 42 to 72 patients with IPBSNHL reacted with a 68-kd protein constituent of inner ear extract. This reactivity was not detected in serum from 11 of 11 patients with otosclerosis, or in eight of eight with Cogan's syndrome. It was found in serum from one of 10 patients with a positive test for antinuclear antibody and in one of 53 normal controls. Antibody to the 68-kd protein was detected in serum from 89% of patients with actively progressing IPBSNHL and none of the 25 patients with inactive disease (P < .001). Patients who were antibody-positive responded to steroid treatment more frequently than did those who were antibody-negative (P < .001). CONCLUSIONS: These results indicate that the presence of circulating antibody to a 68-kd constituent of bovine inner ear extract serves as a marker for IPBSNHL and that its presence correlates with disease activity and responsiveness to corticosteroid treatment.

Laboratory diagnosis of immune inner ear disease.

Immune inner ear disease is a relatively new and distinct clinical entity that produces unexplained, rapidly progressive, bilateral sensorineural hearing loss. The diagnosis is based on clinical manifestations, positive immune laboratory testing, and beneficial response to a trial of corticosteroids. Immune laboratory tests are used to confirm a presumptive clinical diagnosis. The two tests most commonly used are the lymphocyte transformation test and Western blot immune assay. The rationale behind these tests is presented, and the role they play in laboratory diagnosis of immune inner ear disease is discussed.

T cell heterogeneity in patients with common variable immunodeficiency as assessed by abnormalities of T cell subpopulations and T cell receptor gene analysis.

T lymphocyte regulation of immunoglobulin production may be abnormal in some patients with common variable immunodeficiency (CVI). Phenotypic analysis of peripheral blood T lymphocytes from nine patients with CVI was conducted to examine whether an abnormal distribution could be detected in a functionally distinct T lymphocyte subpopulation. The percentage of CD8+ lymphocytes proved to be increased in some patients and decreased in others. In comparison with normal controls, many patients with CVI had reduced percentages of lymphocytes expressing both CD4 and CD45RA, a phenotype associate with naive CD4+ cells. There was no significant difference in CD4+ populations bearing CD29 or leucocyte adhesion molecule-1 (LAM-1) antigens. The pattern of gene rearrangement of the T cell antigen receptor (TCR) was studied using peripheral blood lymphocytes from these patients with CVI. Genomic DNA from freshly isolated lymphocytes as well as from selectively propagated CD4+ or CD8+ populations were examined using Southern blot analysis and a probe for the beta chain of the TCR. A polyclonal pattern of TCR gene rearrangement, without the appearance of dominant non-germline bands, was demonstrated in all patient samples. These data suggest that the T lymphocytes in patients with CVI have a polyclonal pattern of TCR rearrangement despite an abnormal distribution of T cell subpopulations in some patients.

[Familial incidence of post-streptococcal glomerulonephritis]. / Incidencia familiar de la glomerulonefritis postestrepotocócica.

The investigation on siblings of AGN patients has shown a streptococcus carrier evidence of 45%, while glomerulonephritis incidence was 15%. These data allowed us to classify our population as highly susceptible to bacterial dissemination and to the development of non-suppurative complications. Renal compromise was clinical and histologically classified. Subclinical forms showed glomerular lesions of mesangial localization, while clinical forms exhibited variable degrees of cellular proliferation. All patients recovered except one who died of a rapidly progressive form.

Incidencia familiar de la glomerulonefritis postestreptococica. / Familial incidence of poststreptococal glomerulonephritis

El estudio de una poblacion de hermanos de pacientes con glomerulonefritis aguda mostro una incidencia de portadores de estreptococo del 45% mientras que la frecuencia de glomerulonefritis fue del 15%. Estos datos permiten clasificar a nuestra poblacion como altamente susceptible a la diseminacion de esta bacteria y el desarrollo de sus complicaciones no supurativas. El compromiso renal fue caracterizado clinica e histologicamente en las diferentes formas de presentacion. Las formas subclinicas presentaron lesiones glomerulares de localizacion mensangial mientras que las formas clinicas mostraron grados variables de proliferacion celular. Con excepcion de un paciente que murio con una forma rapidamente progresiva, todos evolucionaron hacia una curacion aparentemente definitiva