Cooperation of idiotypic and anti-idiotypic antibodies at the steroid-depended chemical carcinogenesis

Abstract

Immunological research of steroid-depended chemical carcinogenesis in humans is based on positive experience in the clinical usage of selective estrogen receptor modulators and experimental design of immunological methods for human protection from environmental carcinogens. Our study aimed for research of idiotypic antibodies against benzo[a]pyrene, estradiol and progesterone (IgA1-Bp, IgA1-E2 and IgA1-Pg), in connection with anti-idiotypic antibodies specific to estradiol and progesterone (IgG2-E2 and IgG2-Pg) in serum samples of postmenopausal healthy women (HW) and ER+/PR+ stage I breast cancer patients (BCP). Idiotypic antibodies were studied in 402 HW and 475 BCP using ELISA technique, with BP, E2 and Pg conjugated with bovine serum albumin as adsorbed antigens. The anti-idiotypic antibodies were studied using ELISA method and monoclonal antibodies against E2 and Pg as adsorbed antigens. High individual ratios of IgA1-Bp/ IgA1-Pg 1 and IgA1-E2/IgA1-Pg 1 were revealed in 42.1% and 48.5% HW, and in 71.1% and 78.1% of BCP cases (p 0.0001, OR = 5.9 and OR = 3.8, respectively). High IgG2-E2 4 levels were found in 23.4% HW and in 41.2% of BCP group (p = 0.0001, OR = 2.3). Combination of IgA1-Bp/IgA1-Pg 1 with IgG2-E2 4 and IgG2-Pg 2 was more common in HW, than in BCP (29.3% vs 5.8%, p 0.0001, OR = 0.1). Combinations of IgA1-Bp/IgA1-Pg 1with IgG2-E2 4 or with IgG2-Pg 2 were more frequent in BCP, than in HW (12.0% and 31.8% vs 4.9% and 15.2%, accordingly, p = 0.01, OR = 2.7 and p = 0.001, OR = 2.6), as well as combination of IgA1-Bp/IgA1-Pg 1 with IgG2-E2 4 and IgG2-Pg 2 (23.4% vs 9.8%, p = 0.0003, OR = 2.8). Similar specific features were found in HW and BCP when studying IgA1-E2/IgA1-Pg ratio with IgG2-E2 and IgG2-Pg. Nevertheless, high IgA1-Bp/IgA1-Pg 1 or IgA1-E2/IgA1-Pg 1 combined with low IgG2-E2 4 + IgG2-Pg 2 were revealed in HW (27.7% and 28.8%) more frequently, than in BCP (19.7%, p = 0.06 and 17.9%, p = 0.008). Excess of IgA1-Bp and IgA1-E2 levels over IgA1-Pg in combination with high IgG2-E2 and IgG2-Pg levels in HW is associated with ER+/PR+ BC stage I condition and may serve as an marker for preventive BC therapy by the targeted ER modulators.