serum iga in nasopharyngeal carcinoma

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Serum IgA in Nasopharyngeal Carcinoma ASHRAF KHAN, S. HAMEED & Z. HUSAIN After the demonstration of tumour specific antigens by Foley (1953) and Prehn and Maine (1957) a great deal of experimental and clinical data have established the role of humoral immunity in various aspects of malignancy. Serum IgA have been studied in 15 cases of carcinoma naso- pharynx and a significant increase in IgA levels observed have been correlated with the exposure of the mucosa of oral cavity to environment and its stimulation leading to increased synthesis of the secretary antibody (IgA). No correlation with tumour dissemination was observed. The role of Epstein-Barr virus leading to increase in IgA cannot be ruled out. There is increasing body of evidence for the importance of the immune system in the defence against tumour growth. It has been suggested as a major tenet of the theory of immunological surveil- lence, that some immune mechani- sms are involved primarily as a natural defence against neoplasm. Much work has been done to study the role of immunoglobulins in tumour immunity defining clear- /y its potentialities and limitations. Dostolova, et al (1975) and Hughes (1971) have reported a significantly elevated IgA levels in carcinoma orpharynx and larynx. IgG and IgM levels showed no significant differnce as compared to healthy controls. Zejula, et al (1979) reported significantly elevated IgA in Nasopharygeal carcinoma. This increased IgA is correlated with the increased ability of the buccal and respiratory mucosa to synthesize IgA. This study was conducted to assess the secretory activity of the neoplastic Nasopharyngeal mu- cosa, humoral immune status of these patients and to correlate serum IgA level with tumour dissemination. Ashr~f Khan Demonstrator. S. Hameed Professor ~ Chairman. Z. Husain Lecturer. Department of Pathology, Jawaharlal Nehru Medical College A. M. U. Aligarh. Address for reprints : Dr. Ashraf Khan Department of Pathology J. N. Medical College Aligarh Muslim University Aligarh-202 001 (U.P.) India. Material Et Methods The study group comprised of 15 cases of carcinoma Nasophary- nx admitted in the E.N.T. wards of Jawaharlal Nehru Medical College Hospital. The diagnosis was con- firmed by Histhopathological exa- minations. The control group comprised of 17 healthy age matched volunteers. Fig. 1. Agar immunodiffusion plate Quantitative estimation of serum IgA was done in mg/100 ml by single radial immunodiffusion technique of Mancini, et al (1965). The agar immunodiffusion plate as shown in Fig.1 comprises of 20 wells. 4 wells on the left vertically are for serial dilutions of control sera and remaining 16 wells for the study group. Observations There was a statistically signi- ficant increase (p 0.05) in mean serum IgA level in patients with Nasopharyngeal carcinoma when compared with healthy controls (Table I). No significant difference ( 0.05) was observed in metasta- sizing tumours of Nasopharynx when compared with localized tumours (Table II). Discussion Serum IgA studied in 15 cases of carcinoma Nasopharynx demo- nstrated a significant increase and this increase is consistent with the findings of Hughes (1971), Dos- tolove, et al (1975) and Zejula, et al (1979). Mandel, et al (1973) have reported in increase in sali- vary IgA in oropharyngeal carcino- mas which can be correlated with serum IgA. Tomasi, et al (1963), Crabbe, et al (1966) and Tourville et al (1969) suggested that IgA is produced in large quantities by immunologically competent tissues in contact with external environ- ment and also IgA has been shown to act as an antibody with antibacterial, antiviral and isoag- glutinin activity by Butler, et al, (1970), Ishizaka, et al (1965) and Smith, et al (1966). Thus an increased IgA in neoplasms of oral cavity can possibly play a role in host antitumour survveillence me- chanisms. Increased salivary IgA have been correlated with smoking by Mandel, et al (1973), also that smoking is a predispossing factor in the development of oropharyn- geal carcinomas. This increased incidence of oropharyngeal car- cinomas in smokers and alcoholics is further supported by Keller (1967). In the present study 11 patients out of 15 were chronic smokers and 5 had history of alcoholism, only 2 were chronic Indian Journal of Otolaryngology, Volume 37, No. 4, December, 1985 135

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Serum IgA in Nasopharyngeal Carcinoma

ASHRAF KHAN, S. HAMEED & Z. HUSAIN

After the demonstrat ion of tumour specific antigens by Foley (1953) and Prehn and Maine (1957) a great deal of experimental and clinical data have established the role of humoral immuni ty in various aspects of malignancy. Serum IgA have been studied in 15 cases of carcinoma naso- pharynx and a signif icant increase in IgA levels observed have been correlated w i th the exposure of the mucosa of oral cavity to environment and its st imulation leading to increased synthesis of the secretary ant ibody (IgA). No correlation wi th tumour dissemination was observed. The role of Epstein-Barr virus leading to increase in IgA cannot be ruled out.

There is increasing body of evidence for the importance of the immune system in the defence against tumour growth. It has been suggested as a major tenet of the theory of immunological surveil- lence, that some immune mechani- sms are involved primarily as a natural defence against neoplasm. Much work has been done to study the role of immunoglobulins in tumour immunity defining clear- /y its potentialities and limitations.

Dostolova, et al (1975) and Hughes (1971) have reported a significantly elevated IgA levels in carcinoma orpharynx and larynx. IgG and IgM levels showed no significant differnce as compared to healthy controls. Zejula, et al (1979) reported significantly elevated IgA in Nasopharygeal carcinoma. This increased IgA is correlated with the increased ability of the buccal and respiratory mucosa to synthesize IgA. This study was conducted to assess the secretory activity of the neoplastic Nasopharyngeal mu- cosa, humoral immune status of these patients and to correlate serum IgA level with tumour dissemination.

Ashr~f Khan Demonstrator. S. Hameed Professor ~ Chairman. Z. Husain Lecturer. Department of Pathology, Jawaharlal Nehru Medical College A. M. U. Aligarh.

Address for reprints : Dr. Ashraf Khan Department of Pathology J. N. Medical College Aligarh Muslim University Aligarh-202 001 (U.P.) India.

Mater ia l Et Methods

The study group comprised of 15 cases of carcinoma Nasophary- nx admitted in the E.N.T. wards of Jawaharlal Nehru Medical College Hospital. The diagnosis was con- firmed by Histhopathological exa- minations. The control group comprised of 17 healthy age matched volunteers.

Fig. 1. Agar immunodiffusion plate

Quantitative estimation of serum IgA was done in mg/100 ml by single radial immunodiffusion technique of Mancini, et al (1965). The agar immunodiffusion plate as shown in Fig.1 comprises of 20 wells. 4 wells on the left vertically are for serial dilutions of control sera and remaining 16 wells for the study group.

Observations

There was a statistically signi- ficant increase (p 0.05) in mean serum IgA level in patients with Nasopharyngeal carcinoma when compared with healthy controls (Table I). No significant difference ( 0.05) was observed in metasta- sizing tumours of Nasopharynx

when compared with localized tumours (Table II).

Discussion

Serum IgA studied in 15 cases of carcinoma Nasopharynx demo- nstrated a significant increase and this increase is consistent with the findings of Hughes (1971), Dos- tolove, et al (1975) and Zejula, et al (1979). Mandel, et al (1973) have reported in increase in sali- vary IgA in oropharyngeal carcino- mas which can be correlated with serum IgA.

Tomasi, et al (1963), Crabbe, et al (1966) and Tourville et al (1969) suggested that IgA is produced in large quantities by immunologically competent tissues in contact with external environ- ment and also IgA has been shown to act as an antibody with antibacterial, antiviral and isoag- glutinin activity by Butler, et al, (1970), Ishizaka, et al (1965) and Smith, et al (1966). Thus an increased IgA in neoplasms of oral cavity can possibly play a role in host antitumour survveillence me- chanisms.

Increased salivary IgA have been correlated with smoking by Mandel, et al (1973), also that smoking is a predispossing factor in the development of oropharyn- geal carcinomas. This increased incidence of oropharyngeal car- cinomas in smokers and alcoholics is further supported by Keller (1967). In the present study 11 patients out of 15 were chronic smokers and 5 had history of alcoholism, only 2 were chronic

Indian Journal of Otolaryngology, Volume 37, No. 4, December, 1985 135

SERUM IGA IN NASOPHARYNGEAL C A R C I N O M A - - K H A N et al

alcoholics. Thus the protective role of IgA in Nasopharyngeal carcinoma is debatable. Hughes (1971) reporting an increased IgA in oropharyngeal carcinomas sug- gested that since IgA is the pre- dominant immunogobul in class secreted into the mucosai surfaces of nose and mouth and also that local rather than systemic response is necessary to induce the secre- t ion of specif ic IgA (Genco, 1969) so a cancer of such tussues like the oral cavi ty can result in an in- creased synthesis of IgA wi th a consequent increased serum con- centration.

Thus an increase in IgA in Naso- No signif icant difference was pharyngeal carcinomas may be observed in metastasizing Naso- correlated with the possible role pharyngeal carcinomas. When of Epstein-Barr virus in the produc- compared with localized tumours. t ion of these tumours.

TABLE I

Serum IgA in Carcinoma Nasopharynx

Group No. of Serum IgA level (mg/100 ml) 'P' value cases Mean±S.D.

1. Carcinoma Nasopharynx 15 327±82.90 < 0.05

2. Healthy controls 17 220±75.86

S e r u m IgA in Nasopharyngea l Carc inoma

Role of Epstein--Barr virus in relation to Nasopharyngeal car- cinoma have been reported by many workers (Henle, et al, (1977), Suzuki, et al, (1978) ; Coates, et al (1978,). Epstein Barr virus related ant ibody have been studied and high titres have been found in Nasopharyngeal carcinomas.

TABLE II

Serum IgA in Carcinoma Nasopharynx in Relation to Metastasis

Group No. of Serum IgA level (mg/100 ml) 'P" value cases Mean±S.D.

No. 1. Metastasis 05 330±77.27

< 0.05 2. Metastasizing tumours 10 326±89.61

References

1. Butler W.T. Waldman T.A. and Rossen R.D. (1970). Changes in IgA and IgG concentrations in nasal secretions prior to the appearance of viral respiratory infection in man, Journal of Immunology, 105 : 584.

2. Coates, H.I., Neel H.B. and Pearson, G.R. (1978). Immunovirolagic as- sessment of American patients with Nasopharyngeal carcinoma and occult primary tumours, Otolaryn. gology, 83 (3).

3. Crabbe, P.A., and Heremans, J.F. (1960). The distributionjof immuno- globulin containing cells along the human gastrointestinal tract, Gas- trointerolo#y, 51 : 305.

4. Dostolova, O., Shon, E., Wagnerova, M., Jeliner, J. and Wagern W. (1975). Serum immunoglobulin levels in cancer patients. I. Serum immunoglobulins and Primary tu- mour localization, Neoplasma 22: 539.

5. Genco, R.J. and Tauban, M.A. (1969). Secretary gamma A anti- bodies induced by local immuniza- tion, Nature (London), 221 : 679.

6. Henle, W., H.O., J. M. C. and Henl. 12. (1977). Nasopharyngeal carcinoma : Significance ef chanses in Epstein- Barr virus related antibody pattern following therapy, International Journal of Cancer, 20 (5) : 663.

7. Hughes, N.R. (1971). Serum con- 13. centrations of G, A, M immunoglo- bulins in patients with carcinoma, melanoma and Sarcoma, Journal of National Cancer Institute, 46 : 1015.

8. Ishizaka, K., Ishizek, T. and Lee, E.H. (1965). Immunochemical properties 14. of human. A isohaemagglutinin. I. Comparision with G and M glo- bulin antibodies, Journal of Immu- nology, 95 : 197.

9. Mancini, G., Carbonara, A.O. and Heremans, J.F. (1965). Immuno- 15. chemical quantitation of antigens by single radial immunodiffusion. Im- munochemistry, 2 : 235.

10. Mandel, M.A., Dvorak, K. and Decose, J.J. (1973). Salivary immunoglobulins in patients with Oropoaryngeal and Bronchopulmo- nary carcinoma, Cancer, 31 : 1408.

11. Prehn, R.T. and Maine, J.M. (1957). 16. Immunity to methylcholanthrene induced Sarcomas, Journal of na- tional cancer institute, 18 : 769.

Smith, C.B., Purcell, R°H. and Bellanti, J.A. (1966). Protective effect of antibody to parainfluenza Type I virus, New England Journal of Medicine, 275 : 1145.

Suzuki, T., Kataiw, A. and Oboski, S. (1978). EBV determined nuclear antigen in malignant epithelial cells of Nasopharyngeal carcinoma. CANN, 69 (I) : 133.

Tomasi, T.B.Jr. and Zigelbaum, S. (1963). The selective occurence of

A-globulins in certain body fluids, Journal of clinical investigations, 42 : 1552.

Tourville, D.R., Adler, R.H. and Bienenstock, J, (1969). The human secretary immunoglobulin system : Immunohistological Ilocalization of

A, Secretary "Piece" and lacto- ferrin in normal human tissues, Journal of experimental medicine, 129 : 411.

Zejula, J. (1979). Serum immuno- globulins in Oropharyngeal carci- noma. Cesk otolaryngeal, 28 (5) : 276.

136 Indian Journal of Otolaryngology, Volume 37, No. 4, December. 1985