Theoretical and practical implications for plasmapheresis in autoimmune inner ear disease.

Immune-mediated inner ear disease, by convention called autoimmune inner ear disease (AIED), has established clinical profile guidelines for diagnosis. Treatment consists of steroid and/or cytotoxic drug immunosuppression. The role of plasmapheresis (PMP) in the treatment of AIED has not been defined. Lack of a precise serological marker prevents accurate immunological understanding. Definition is, of course, difficult in a disease whose natural history is not well delineated. Successful use of PMP in one steroid and cytotoxic drug intolerant patient with AIED led to its use in a total of eight patients. The rationale for PMP was based on its known effectiveness in other autoimmune diseases and thus, its potential use in AIED. Improved auditory function occurred in 6 of the 8 patients, 3 of whom have been followed for over 3 years. Three of the six no longer require immunosuppressant medication. PMP can be used as an alternative or adjunctive therapy in AIED. These preliminary results suggest PMP can stabilize or improve auditory and vestibular symptoms in selected patients. Its use as a first line therapy followed by cytotoxic immunosuppressants bears consideration.

Induction of experimental endolymphatic hydrops by immunologic techniques.

Immunologic techniques have been used by many investigators to produce experimental endolymphatic hydrops models. These techniques, however, have achieved little success in producing models simulating the idiopathic endolymphatic hydrops of Meniere's disease, in which no inflammatory changes occur in the perilymphatic spaces. In this study, the antigen horseradish peroxidase (HRP) was injected into the endolymphatic sacs of ninety guinea pigs that had been systematically sensitized to this antigen. Endolymphatic hydrops was induced in sixty-seven of the subjects, sixty-four of which showed no inflammatory changes in the perilymphatic spaces. The endolymphatic sacs of the affected guinea pigs were packed with soft granulation tissue induced by immunologic mechanisms; it is felt that the hydrops was caused by disturbances in endolymph absorption resulting from these tissue formations. Our results suggest that the introduction of antigens into the endolymphatic sac may prove useful in producing endolymphatic hydrops with characteristics similar to those occurring in Meniere's disease.

Effect of a middle ear immune response on inner ear antibody levels.

The effect of a middle ear immune response upon antibody levels in the perilymphatic compartment of the inner ear was investigated in the guinea pig. Animals were systemically sensitized with keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA) until high circulating levels were achieved. The middle ear cavity was then challenged with KLH, resulting in a vigorous immune response with effusion and mucosal inflammation. Antibody levels against KLH and BSA were then compared in serum, middle ear effusions, and perilymph. Anti-KLH levels in perilymph were found to increase substantially during middle ear response to challenge, while the anti-BSA levels did not, indicating a local origin for the anti-KLH antibody. The most likely explanations for these findings are inner ear antibody originated in the middle ear and diffused across the round window membrane, or antigen diffused across the round window membrane and evoked local production of antibody within the inner ear.

Antibody activity in perilymph from rats with type II collagen-induced autoimmune inner ear disease.

Rats were immunized with native type II bovine collagen to induce autoimmune inner ear disease, and the antibody activity in the inner ear fluid was measured. Antibody activity against type II collagen was detected in the perilymph at about 10% to 20% of serum level. Thus, the presence of antibody against type II collagen in inner ear fluid may imply an immune injury mechanism in inner ear diseases.

Endolymphatic hydrops and III type allergic reaction.

IgG antibody and complement are both present in endolymphatic fluid, and it is possible that immune complex may form in endolymphatic fluid. However, there are still obscure points as to whether endolymphatic hydrops is due to immune complex, but it is quite possible that it is only one causative factor in endolymphatic hydrops.

Antigenicity and protein content of perilymph in acoustic neuroma patients.

11 acoustic neuroma patients, exhibiting cell-mediated immunity in vitro against acoustic neuroma extract, were tested for cell-mediated immunity in vitro against perilymph samples from other acoustic neuroma patients. 14 of 21 perilymph samples were antigenic. None of three healthy persons reacted against antigenic perilymph samples. The perilymph antigenicity was reproducible and negatively correlated to the perilymph sample volume. Differences in sample volume could not be ascribed to admixture of endolymph, cerebrospinal fluid, plasma or blood. The perilymph protein concentration varied from 31 to 54 g/l. Gel electrophoresis of perilymph proteins revealed less staining in the alpha-region compared to plasma proteins and a distinct band in the pre-gamma region absent in plasma. Tau-transferrin was not detected in any of 13 samples. The findings support that the cell-mediated immune response against acoustic neuroma extract may be mediated through release of antigen(s) to the perilymph.

Immunological analysis of IgG and other protein fractions in endolymph obtained from endolymphatic sac of Meniere patients and a control.

During endolymphatic sac surgery on patients with Meniere's disease, very small amounts (1 microliter) of the intra-sac endolymph were obtained with micro-glass pipets. An immunological assay of microanalysis of the protein by the single radial immunodiffusion (SRID) method was applied to 2 patients, one with bilateral involvement and the other unilateral. Among the protein fractions Alb, IgG, IgM, IgA, C3, C4, transferrin and alpha 2M, the concentrations of IgG were relatively higher, especially in the Meniere patient in the active stage. From 2 other patients and a control deaf patient with temporal bone fracture, the same amounts of endolymph were obtained, accompanied by a tiny specimen of the outer wall of the sac. When a radio-immunological procedure was applied to the endolymph and the homogenized sac, the specific concentration of IgG was higher in the Meniere patients than in the control.

Type II collagen-induced autoimmune endolymphatic hydrops in guinea pig.

Endolymphatic hydrops was induced in guinea pigs by immunizing them with native bovine type II collagen. Histopathologic changes consisted of moderate extension of the Reissner's membrane, spiral ganglion degeneration, atrophied organ of Corti, and mild atrophy of the surface epithelium in the endolymphatic duct. These findings suggest that an immune response directed against type II collagen--a type of collagen found in the membranous labyrinth, subepithelial layer of the endolymphatic duct, spiral ligament, and enchondral layer of the otic capsule--may induce endolymphatic hydrops.

Immunology of the inner ear: response of the inner ear to antigen challenge.

The relationship of the inner ear to host immunity and the immunoresponsiveness of the inner ear to antigen challenge were investigated. A radioimmunoassay was used to quantitate antibody titers to keyhole-limpet hemocyanin generated in the serum, perilymph, and CSF of guinea pigs following systemic or inner ear immunizations. The results of these experiments demonstrate (1) the blood-labyrinth barrier is analogous to the blood-brain barrier with respect to immunoglobulin equilibrium, (2) the inner ear is capable of responding to antigen challenge, and (3) the inner ear is an effective route for systemic immunization.

Immune complexes in middle ear fluid in chronic secretory otitis media.

Data on 87 patients (113 ears) with chronic secretory otitis media (SOM) are reported. The bacteriological analysis of the middle ear fluid (MEF) revealed Streptococcus pneumoniae in 7% of ears, Hemophilus influenzae in 9%, opportunistic bacteria in 20%, while 64% of the samples showed no growth. Free capsular polysaccharide pneumococcal antigens were found in 5% of the MEF samples using counterimmunoelectrophoresis (CIEP) with Omniserum containing 83 different pneumococcal polysaccharide types. Heating of the samples to disrupt the immune complexes increased the frequency of positive samples to 27%. These findings, together with the frequent occurrence of S pneumoniae and H influenzae in the nasopharynx, strongly support the opinion that chronic SOM in a considerable number of cases is an immune complex disease.

Immunologic study on the inner ear. Immunoglobulins in perilymph.

The immunoglobulin composition of perilymph (PL) was measured using electroimmunodiffusion, and transfer of serum antibodies to PL was studied using a passive hemagglutination test in chinchillas and guinea pigs. The mean values of IgG an albumin in PL were two to four times greater than those in CSF. In guinea pigs, IgA was found in 93% of the PL and 32% of the CSF samples, but in chinchillas only trace amounts of IgA were found in 50% of the PL and 15% of the CSF samples. No IgM was detected in PL or CSF of either species. This study suggests that a greater portion of the immunoglobulins in PL probably is derived from perilymphatic blood vessels as a filtrate and that the perilymphatic inner ear immune system is independent from that of the CSF.

Pharmacokinetics of gentamicin in perilymph and endolymph of the rat as determined by radioimmunoassay.

The kinetics of gentamicin in the inner ear fluids of the rat were studied with a sensitive radioimmunoassay. Continuous infusion over a broad range (7.5--150 micrograms/min) was used to obtain equilibrium. The lowest rate of infusion produced plasma concentrations after 45 min that were within the range of peak serum levels desirable in humans. The purity of perilymph and endolymph was ensured by measurement of sodium and potassium concentrations. The concentration of gentamicin in perilymph was linearly related to its concentration in plasma, which depended on the rate of infusion. After six days of constant infusion of gentamicin at 15 microgram/min, the concentrations in plasma, perilymph, and endolymph averaged 25.8, 5.1, and 1.2 micrograms/ml, respectively, for five of 11 rats. Gentamicin cleared from the perilymph with a half-life of 3 hr.