Serum immunoglobulins specific for intracellular proteins of squamous cell carcinoma.

OBJECTIVE: To determine an autologous humoral immune response to squamous cell carcinoma (SCC) intracellular proteins in patients with SCC. DESIGN: Intracellular proteins were isolated from 25 different cultured SCC lines. The proteins were used as a source of antigens to measure IgA, IgE, and IgG responses in the serum samples of patients and controls. Antibody response was assessed in both unfractionated and fractionated intracellular proteins. PATIENTS: The serum samples of 65 patients with SCC and of 65 age- and gender-matched controls were tested. RESULTS: Antibodies to SCC intracellular proteins were detected in the serum samples of 40 (62%) of the 65 patients with SCC and in the serum samples of 46 (71%) of 65 controls. Thirty (46%) of the patients with SCC and 40 (62%) of the controls had IgE responses, 18 (28%) of the patients and one (2%) of the controls had IgA responses, and 17 (26%) of the patients and 14 (22%) of the controls had IgG responses. An inverse relation was noted between detectable IgE responses and IgA or IgG responses in the patients and the controls. The analysis of antibody response indicated that 28 molecules were recognized predominantly by the serum samples of patients with SCC, but not by the serum samples of controls. CONCLUSIONS: A substantial proportion of patients with SCC and of controls exhibited an autologous humoral immune response to SCC intracellular proteins. The IgE responses to SCC intracellular proteins were inversely related to IgA or to IgG responses. Different antibody isotypes normally cause markedly different immune functions, and may suggest different roles for the existent immune responses to SCC antigens. We identified many tumor-associated antigens that were selectively recognized by the serum samples of patients with SCC. These antigens could be used to define molecular studies of immune surveillance and selection, and may represent appropriate targets for immunotherapy.

Fluoride: an adjuvant for mucosal and systemic immunity.

Fluoride, the agent responsible for reduction of dental caries worldwide, and a recognized proliferative agent, is a potent adjuvant when given intragastrically to rats. Intragastric fluoride causes increases in the size and cellularity of the Peyer's patches and mesenteric lymph nodes as well as the number of plasma cells secreting IgG and IgA antibodies to ovalbumin given in their drinking water. Rats ingesting NaF and fed OA showed a significant increase in surface immunoglobulin expression on lymphocytes from the Peyer's patches and mesenteric lymph nodes. The frequency of CD4+ T cells in these lymphoid tissues was elevated while that of CD8+ T cells was significantly decreased. In separate experiments, rats parenterally immunized with myelin basic protein (MBP) and fed NaF twice weekly, had significantly elevated serum IgG antibody activity to MBP compared to similarly immunized rats not receiving NaF. The supplemental fluoride prescribed for infants and especially that which is inadvertently ingested by children and adults given fluoride gels, is within the concentration range of that which produced the effects we observed in rats. The adjuvant effect we describe thus has relevance for fluoride therapy worldwide.

Humoral immunity in root caries in an elderly population. 1.

IgA, IgG and IgM antibody activity (ELISA Units/ml) to Streptococcus mutans, Actinomyces viscous and Escherichia coli CF8 in serum, parotid saliva and whole saliva was measured using the amplified ELISA (a-ELISA) while the concentration (microgram/ml) of each isotype of immunoglobulin as well as albumin and lactoferrin, was determined using sandwich ELISAs. Selection of suitable reagents from those commercially available was based on specificity tests using purified human immunoglobulin; most polyclonal reagents required further absorption to attain class specificity. Cross-absorption studies indicated the absence of patient antibodies that were cross-reactive among the bacteria studied, except for IgM in some cases. Expression of response in ELISA Units (E.U.) per microgram of immunoglobulin, i.e. specific activity, revealed that IgG specific activity was significantly higher in parotid saliva than in either whole saliva or serum for all bacteria studied; serum and whole saliva did not differ except for the higher specific activity in whole saliva to E. coli. The value of one E.U. was determined using the Comparative Antibody-immunoglobulin Capture Assay (CACA). Using this novel method, we estimated that about 0.05 percent of serum IgA was specific for Streptococcus mutans, 0.008 for Actinomyces viscosus and 0.004 for Escherichia coli CF8. The percentage of specific IgM antibodies was higher than for IgA and IgG. The concentration of IgA anti-Streptococcus mutans, Actinomyces viscosus and Escherichia coli levels are approximately 92 ng/ml, 25 ng/ml and 16 ng/ml in whole saliva and 46 ng/ml, 9.4 ng/ml and 6.3 ng/ml in parotid saliva.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro modulation of natural killer cell activity in non-Hodgkin's lymphoma patients after therapy.

The depressed natural killer (NK) activity, anti-body-dependent cellular cytotoxicity (ADCC) and NK cytotoxic factor cytotoxicity in untreated non-Hodgkin's lymphoma patients were found to be elevated after chemotherapy. In vitro treatment of the effector NK cells with interferon alpha could augment the NK activity in normal subjects and treated patients to a comparable degree. Chemotherapy mainly affected the post-binding events in the NK cytotoxic process by causing an increase in the active killing potential of the NK cells. This study provides a better understanding of changes in the NK cytotoxic mechanism in non-Hodgkin's lymphoma patients and the role of interferon in this process.

Natural killer and antibody-dependent cellular cytotoxicity in cervical carcinoma patients.

Natural killer (NK) cell activity and antibody dependent cell-mediated cytotoxicity (ADCC) was measured in 62 untreated cervical carcinoma patients and 25 normal healthy women, using a short-term chromium release assay. A significant reduction in NK and ADCC activity was observed in disseminated disease than in localized disease, when compared with normal donors. The majority of the patients received radiotherapy and both NK and ADCC activity recovered after therapy. Furthermore, interferon-alpha was demonstrated to augment NK activity of peripheral blood mononuclear cells from healthy donors as well as patients. Also large granular lymphocytes separated on Percoll density gradient were the same in number in both the populations studied, although in cervical cancer there seemed to be a defect in killing activity.

Isolation and dissociation of immune complexes from pleural effusions of lymphoma patients.

Immune complexes (IC) isolated from pleural effusions of lymphomas with favorable and unfavorable prognoses were of IgG type. These IC were further dissociated by ion exchange chromatography using 8 M urea. The antibody was found to be a high molecular weight protein (1.5 X 10(5) daltons) and reacted with antihuman IgG immunologically while a second peak obtained on ion exchange chromatography may be an antigen moiety with a molecular weight of 3.2 X 10(4) daltons as it reacted immunologically with the antibody. Strong cytoplasmic fluorescence was observed with various cell suspensions of lymphomas when reacted with the antibody preparations. The antisera raised against two different antigen fractions prepared from two lymphomas--nHL and LL showed positive fluorescence with both nHL and LL suspensions. The absorption of these rabbit antibodies with individual cell extracts or with antigen preparations also entirely blocked the cytoplasmic staining. The antigen moiety (PK-II) may have a common origin in the disease process. Pleural effusions from patients with unfavorable and favorable prognoses showed identical patterns of separation of IC components.

Immune status in untreated cervical cancer patients.

Eighty untreated cervical carcinoma patients were tested for their immune status by evaluating levels of circulating T and B lymphocytes and lymphocyte reactivity to PHA. Significant reduction in T lymphocytes and depressed lymphocyte reactivity to PHA was observed following the progression of the disease. However, B lymphocyte levels remained unaffected. The general impairment observed in cell-mediated immunity was found to be more pronounced in the disseminated disease than in the localized group.