Other Tissue Autoantibodies

Several workers reported increased incidence of smooth muscle antibodies of the IgG or IgM type in malignancies [32, 34, 37]. These autoantibodies were described in several malignant tumors including melanoma [52], carcinoma of the lung [32], breast [37], ovary, lung [34] and cervix [32], In one study [37] the presence of antismooth muscle antibodies was correlated with poor prognosis in patients with breast cancer. Since antismooth muscle antibodies typically are raised in chronic active hepatitis it was suggested that their presence in malignancies may be associated with liver metastases. However, anti-smooth muscle antibodies were found in patients with localized malignancies [52] and this hypothesis seems unlikely. Other autoantibodies that were found to be increase in malignancies include antiparietal cell antibodies [40], thyroid autoantibodies, anticytoplasmic antibodies [40] and antiperinuclear antibodies.

7. AUTOANTIBODIES IN MALIGNANCIES ARE THEY TRULY INCREASED?

The finding of increased incidence of autoantibodies in malignancies caused much excitement and hope among oncologists and immunologists. Some investigators have raised the possibility that autoantibodies may be the long awaited for tumor markers and may even serve as serological screening test for malignancies [33], Several hypotheses have been proposed to explain the production of autoantibodies in malignancies including host immune-reactions to tumor-associated antigens [34], antigenic stimulation as a result of enhanced destruction of malignant cells [37], immune dysregulation induced by the neoplastic process, antigenic stimulation as a result of therapy [47], and production of autoantibodies by the tumor itself as in the case of B-cell lymphomas and monoclonal gammopathies. However, autoantibodies and malignancy may both be associated with another condition rather than with each other. Since autoantibodies and cancer are known to be more prevalent in old age we investigated whether or not the associa tion between neoplasia and autoimmunity results from increased incidence of both conditions in senescence. In our preliminary investigation [61] we studies 139 patients (55 of whom were aged 60 years and younger, and 84 were older than 60 years) suffering from a variety of malignant tumors for ANA, RF and antiery-throcyte antibodies (Coomb's test). There was no significant difference between the incidences of ANA and RF in the young patients and in the young controls and similarly, there was no significant difference between the incidences of ANA and RF in the elderly cancer patients and in the elderly controls. Our results suggest that the reported high incidence of ANA and RF in malignancies is a result of the old age of these patients rather than the tumor itself. However, the incidence of antierythrocyte antibodies was significantly higher in the patients than in the controls. This study was later extended to test a large battery of autoantibodies and the malignancies were grouped into lymphomas and solid tumors. Sera from 164 patients with carcinomas (71 with breast cancer, 30 with colonic carcinoma, 16 with cancer of the prostate, 11 with lung cancer, 9 with melanoma, and the rest with other solid tumors) were analyzed for the presence of autoantibodies to ssDNA, dsDNA, Poly (I), Poly (G), cardi-olipin, histones, RNP, Sm, Ro(SSA) and La (SSB) [62], No distinction could be made between these patients and a comparative group composed of age-adjusted healthy subjects in the levels of antibodies to these autoantigens. This finding remained valid after further subgrouping the patients according to age, sex and histologic origin of the tumor. In contrast, a further analysis of 84 patients with Hodgkin's lymphoma and 55 patients with non-Hodgkin's lymphomas for the presence of autoantibodies to the same autoantigens, have shown that significant increase in the incidence of anti-ssDNA antibodies, anti-RNP, and anti-Sm antibodies when compare to normal age matched controls. With all other autoantibodies examined no significant difference could be observed in the incidence between lymphoma patients and controls [45]. In summary the association between malignancies and autoantibody production seems more complicated than previously believed. The increased incidence of anti-ssDNA, Sm and RNP in patients with lymphomas reflects in our opinion an increased proportion of natural autoantibody producing lymphocytes, which are expanded in the malignant process. This is analogous to our findings in monoclonal gammopathis [59, 60]. However the increased incidence of many (but not all) autoantibodies in the sera of patients with solid malignancies may well reflect the older age of these patients rather than be a result of the tumor itself. However, further analyses with more autoantibodies and larger series of patients with specific tumors are needed to clarify this complex subject.

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