Rheumatoid factor and tumor-host interaction.

Abstract

In this survey for rheumatoid factor (RF) seropositivity on patients with neoplasms, an 85% rate of positive screening tests was recorded under certain circumstances. This high rate of RF seropositivity occurred after irradiation and/or chemotherapy of breast and lung cancers. Treated patients with breast cancers who had no evidence of residual tumor had an 89% rate of positive RF tests. Conversely, the incidence of RF seropositivity was low among untreated patients with similar tumors and treated patients with glioblastomas or multiple myeloma. The administration of cytotoxic drugs (e.g., azathiprene) was not itself associated with RF production even in renal allograft recipients. The data indicate that RF production occurs frequently after therapy of certain tumors and suggest that in these circumstances RF may be an expression of tumor-host interaction.Rheumatoid factor (RF) is detected by routine laboratory techniques in serum from <4% of healthy adults under 65 years of age (1-8). About 13-20% of unselected patients with malignancies are RF seropositive (1, 4, 5), and RF has been eluted from neoplastic but not from adjacent normal tissues (5). The relevance of this antibody response to tumor-host interactions is not known, nor are circumstances that cause it to occur.Most RFs are IgM antibodies to antigenic determinants in IgG. In general, IgM is a more effective activator of complement than IgG (6, 7). However, the effect of IgM-RF on complement mediated reactions is variable (8-11). For example, IgM-RF induces complement-mediated neutralization of herpes simplex virus complexed to IgG antibody (9). However, RF may inhibit complement-mediated phagocytosis (10) and lysis (11) administration of various chemotherapeutic agents intravenously in dose schedules dictated by patient weight, clinical status, and drug tolerance. These drugs included cyclophosphamide, vinblastin, methotrexate, 5-fluorouracil, thio-TEPA, and steroids. Multiple myeloma was treated with irradiation, melphalan, and, in selected cases, steroids. Glioblastomas were treated with irradiation to the head and with steroids. Most patients had received prolonged courses of therapy before their serum was tested. Nineteen patients with breast cancer had no apparent residual tumor after radical mastectomy and had received "prophylactic" irradiation and chemotherapy before they were tested. Of the patients receiving cytotoxic drugs, which were administered for immunosuppression, 11 were renal allograft recipients and 10 had multiple sclerosis. The renal allograft recipients were receiving 100-175 mg of azathioprene and up to 20 mg of prednisone daily; patients with multiple sclerosis were receiving azathioprene at 50 mg/day. Sera were tested for RF at 1:20 dilutions with glycine-saline buffer using latex particles coated with Cohns Fraction II (Hyland Laboratories). RESULTSThe results of the serologic survey for RF are listed in Table 1

Tumor-Associated and Systemic Autoimmunity in Pre-Clinical Breast Cancer among Post-Menopausal Women

“…In the source population from which our sample was derived, RF was significantly higher in women with ANA antibodies (Supplemental Table S1), but in our sample, this difference was only significant in women who became cases and not in controls (Table 1). We are aware of only one previous study showing elevated RF in breast cancer cases [34]. Further studies are warranted.…”

Circulating immune complexes as markers of response to chemotherapy in malignant teratomas and gestational trophoblastic tumours

“…Cytotoxic drugs also affect antibody production, and it has been suggested that the effect is particularly marked on T-suppressor-cell function (Diamantstein et al, 1979;Athanassiades et al, 1978). Rheumatoid-factor levels have been shown to rise in patients receiving treatment for breast and bronchial cancer (Twomey et al, 1976) and this may reflect a more generalized disturbance of antibody production leading to increased autoantibody formation and perturbation of idiotypeanti-idiotype interactions. A recent review by Roitt et al (1981) illustrates the complexity of idiotypic networks in control of antibody production and hence the difficulty of predicting the effects of cytotoxic chemotherapy in human disease.…”

Circulating immune complexes in patients with lung cancer.

“…'14This was originally stimulated by the descript-ion of faetors in the serum of tumour-bearing patients and animals which interfere with cell-mediated immunity.5 It has also been suggested that circulating or cell-,bound immune complexes may be responsible for the relatively high frequency of serum antiglobulin responses in cancer patients,6 7 and signs and symptoms of so-called "immune complex disease" may be seen in patients with cancer. 9 More recently it has been suggested that immune complexes cause synthesis and release of prostaglandins and release of lysosomal acid hydrolysases from macrophages.…”