Toyoharu Yoshida

Middle ear effusions. Quantitative analysis of immunoglobulins.

Quantitative analysis of immunoglobulins (IgG, IgA and IgM) by radial immunodiffusion technique and double diffusion analysis of secretory immunoglobulin A (SIgA) were performed on specimens of middle ear effusion for the purpose of investigating the nature of middle ear effusion. Specimens consisted of 34 serous (15 acute and 19 chronic type) and 15 mucoid effusions (9 acute and 6 chronic type). Mean values of the IgG level in effusions and sera of each category were nearly the same. The IgA concentrations of mucoid effusions were significantly higher than those in serous effusions. Mean values of the IgM level in effusions of acute and chronic cases of both categories were lower than those in the sera. SIgA was found in 9 out of 34 (26.5%) serous effusions, while 14 out of 15 (93.3%) mucoid effusions were found to have SIgA. Results of this study suggest that middle ear effusion is a mixture of the transudate from the serum and of secretion by secretory cells present in the mucosa of the middle ear cavity; and that the nature of the mucoid effusion is similar to exudate, while the serous effusion for the most part comes from the serum.

Immunoglobulin E (IgE) in Middle Ear Effusions

This study was undertaken to further clarify the relation of atopic allergy to otitis media with effusion. Ninety-six specimens of middle ear effusions and corresponding sera were collected from 92 patients, and each sample was quantitatively measured by a radioactive single radial diffusion (RSRD) technique for immunoglobulin E (IgE) concentration. Specimens consisted of 70 serous effusions (38 acute and 32 chronic) and 26 mucoid effusions (10 acute and 16 chronic). The mean concentration of IgE in the serous effusions was 143.1 ± 28.7 ng/ml, and in the corresponding sera 227.5 ± 40.7 ng/ml. The mean concentration of IgE in the mucoid effusions was 221.7 ± 48.9 ng/ml and in the corresponding sera 398.0 ± 81.5 ng/ml. The difference between these values was not statistically significant. In both mucoid and serous types the mean IgE concentration was lower in the effusions than in the sera from the same patients, but this difference was not statistically significant. The mean value of the IgE concentration in mucoid effusions was higher than in the serous effusions, but this difference was not significant. Three of 70 serous effusions (4.3%) and 4 of 26 mucoid effusions (15.4%) had an IgE concentration exceeding 500 ng/ml. In only 2 of the 96 cases (2.1%) did the IgE concentration in effusion exceed both the 500 ng/ml level and the IgE concentration in the corresponding serum. Results of this study suggest that IgE in middle ear effusions, rather than being a local product, may be derived from the serum, and also that the fluid is not an atopic allergic effusion.

Secretory Immunoglobulin a (SIgA) in Middle Ear Effusions; A Further Report

Immunochemical and immunofluorescent studies of secretory immunoglobulin A (SIgA) in otitis media with effusion were carried out to investigate the local immunologic defense system and secretory activity in the middle ear. SIgA was isolated from pooled middle ear effusions by an immunoadsorbents technique and its antigenicity and subunit structure compared with SIgA derived from other external secretions, such as saliva, nasal discharge, and colostrum. The antigenicity and subunit structure of the isolated SIgA from middle ear effusions were identical or very similar to those of SIgA obtained from other external secretions. Radioimmunodiffusion analysis revealed that SIgA was present in 43 of 47 (91.5%) cases of serous middle ear effusion, whereas the sera from only 3 of 47 (6.4%) of these patients was found to have SIgA. Immunoelectrophoresis, using anti-SIgA antiserum, and radioimmunoelectrophoresis detected free SC (secretory component) in 1 of 47 (2%) serous and 6 of 30 (20%) mucoid effusions. Apices of epithelial cells and glandular acinar cells of the middle ear mucosa obtained from patients with otitis media with effusion were stained specifically with anti-SC antibodies. Findings of the study would suggest: 1) that the middle ear maintains the local immunologic defense system, as do respiratory tracts and salivary glands, and 2) that while serous middle ear effusions are a mixture of normal middle ear secretions bathing the membrane surface and transudates from serum, mucoid effusions are the result of enhanced epithelial secretory activity and transudates.

Quantitative Determination of Secretory Immunoglobulin a (SIgA) in Middle Ear Effusions

For the purpose of investigating the nature of middle ear effusion, quantitative analysis of secretory immunoglobulin A (SIgA) by radioactive single radial diffusion (RSRD) technique was performed on specimens of middle ear effusion and serum from the corresponding patient. Specimens consisted of 61 serous effusions (32 acute and 29 chronic type) and 29 mucoid effusions (9 acute and 20 chronic). The mean value of SIgA concentration in the serous effusions was 212.7 ± 13.5 μg/ml and that in sera from these patients was 27.0 ± 3.0 μg/ml. In the mucoid type the mean value of SIgA in effusions was 357.7 ± 13.2 μg/ml and that in sera was 24.3 ± 2.8 μg/ml. The difference in the mean value of SIgA concentration between the serous and mucoid types of effusions was statistically significant. The mean value of SIgA concentration in serous effusions was eight times that in sera from these patients and in mucoid effusions the SIgA value was approximately 14 times that in sera. The calculated percentage of SIgA in the total IgA of middle ear effusions was 11–12% in both the serous and mucoid categories. The percentage in sera was about 1%. Results of this study indicate that all middle ear effusions contain appreciable amounts of the secretory element, although the transudate from serum is the major component of effusion, and support an hypothesis that while serous middle ear effusions are a mixture of normal ear secretions bathing the membrane surface and transudates from serum, mucoid effusions are the result of enhanced epithelial secretory activity and transudates.

Secretory immunoglobulin A (SIgA) in middle ear effusions. Observation of 160 specimens.

Immunochemical studies of secretory immunoglobulin A (SIgA) in middle ear effusions were attempted for the purpose of investigating the existence of the local immunologic defense mechanism and the local protein synthesis in the middle ear. SIgA was isolated from normal human parotid secretions by means of DEAE-cellulose column chromatography and G-200 Sephadex gel filtration. Antiserum against SIgA was made by immunizing a rabbit with the SIgA isolated from the parotid secretions. Antisecretory piece antiserum was made by absorbing the anti-SIgA antiserum with pooled normal human sera. Immunodiffusion analysis of SIgA was performed on 160 specimens of middle ear effusion from patients with otitis media with effusion. Seventy-five of 160 (46.9%) specimens were found to have SIgA. In the serous category 5 of 41 (12.2%) acute cases were positive while 24 of 59 (40.7%) chronic cases were positive. One of 2 acute cases of the seropurulent effusions showed the positive reaction and 2 of 3 cases of the purulent type were positive. In the mucopurulent type 2 of 4 acute cases were positive and all 3 chronic cases were positive. In the mucoid type 9 of 14 (64%) acute cases gave a positive precipitation line while 29 of 33 (87.9%) chronic cases gave the positive reaction. The appearance of precipitation line developed with effusions varies from very faint to distinct. However, as a rule the line of the mucoid, mucopurulent and purulent effusions was strong. Since SIgA is the predominant immunoglobulin in external secretions but is not present or is at very low concentration in normal sera, findings of this study suggested that the middle ear lining membrane possesses the secretory function similar to the epithelium of other external secretory tissues, and suggested the hypothesis that the middle ear epithelium shares the local immunologic defense system as that of respiratory epithelium.

Radioimmunoassay of IgE in Middle Ear Effusions

Fifty-six sample pairs of middle ear effusions and sera obtained from patients with otitis media with effusion were investigated for The IgE antibody activity against mites, using radioallergosorbent test (RAST) which was recently developed as an in vitro allergy test. The IgE concentrations were also determined by radioimmunosorbent test (RIST). Results showed that the IgE antibody activity against this allergen was found in 5 middle ear effusions and 3 sera. Four of 5 patients with the positive RAST test had nasal allergy or signs suggesting allergy. Theree were two middle ear effusions which seemed to be an allergic fluid. However, findings in the present study do not suggest that middle ear effusions result from the direct allergic reaction induced by mites in the mucous membrane lining the middle ear cavity.

Otitis media with effusion: specific antibody activities against exotoxins in middle ear effusions.

Findings of recent immunologic studies on otitis media with effusion indicate that antibodies in middle ear effusions can either originate from serum and/or from local production in the middle ear cavity and Eustachian tube. Determination of specific antibody activity of different immunoglobulin classes in effusions and sera against certain bacterial antigens may aid in a better understanding of the pathogenesis of otitis media with effusion. A radioimmunosorbent assay was employed in the present study to determine specific antibody activity against streptolysin or staphylolysin. Although these antibody activities were mainly limited to IgG and IgA class antibodies in effusion as well as in serum, it was also found that SIgA of various types of the effusion possesses the antibody activity against these exotoxins. Findings of this study suggest that a local immunity functions in the middle ear cavity of patients with otitis media with effusions and that bacterial infection may contribute to the development of middle ear effusion in certain cases.

Histiocytic medullary reticulosis with involvement of the nose.

A case of histiocytic medullary reticulosis in which nasal involvement was predominant is reported. The patient was a 33‐year‐old woman with a 14‐month history of unilateral nasal stuffiness. The diagnosis was established by antemortem examination of films of bone marrow aspirates and by clinical features including fever, wasting, hepatosplenomegaly, anemia, and leukopenia. The histologic examination of autopsy specimens disclosed proliferation of histiocytes, which ingested nuclear debris and erythrocytes, in the necrotic lesion of the nose, sternal bone marrow, liver, spleen, thymus, uterus, ovali, and ileum. On reviewing literature on this subject, such a case of histiocytic medullary reticulosis which predominantly involves the nose is very rare.