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Research on Neurofibromatosis (NF) has been directed at understanding what determines disease quiescence, exacerbation, and the possible malignant evolution. Studies on NF have examined the role of genetic oncosuppression in the evolution of the defence against the non-self. Paraffin fixed specimens of benign and malignant neoplasia, occurring in patients with NF1 and NF2, were tested for the presence of p53: a reliable marker of genetic oncosupression. The wild type variant of p53 is expressed in malignant neoplasia, and is usually not expressed in benign tumors. Contrariwise, an immune reaction it is seen in benign tumors and is practically absent in malignant tumors. Evidence of protein p53 in the various malignant neoplasias studied by our group seems to reflect the up-regulation on the oncosuppresive genetic potential that occurs while there is a lack of immunological defence. In the presence of an immunological defence, the expression p53 is normally not seen e.g. plexiform neurofibromas. The evolution of the various neoplastic types here reported was the same as that reported by current clinical and experimental models: the cell's defective genes are no longer suppressed and after activation the genes undergo initiation, promotion, and the cell sustains inflammatory-immune reactions that lead to fibrosis; what follows is a variable period of apparent quiescence. Severe pathogenic stimuli may act on predisposed cells and deteriorate pre-existing genetic damage, casting the cell into a phase of dysplastic or neoplastic proliferation that overcomes the body's defences. Hope for future therapy lies in the development of drugs that can either mimic the immune system or the proteins encoded by the oncosuppressor genes.

Considering the more recent physiopathogenetic advancements in neurofibromatosis (NF), we propose to employ novel instrumental and laboratory procedures for the immunological and clinical surveillance of NF. In NF the evolution of the non-self can lead to disease expansion, at times transforming into malignancy. Contemporarily, the resulting immunological reactivity can either lead to the type of fibrosis that one sees in paraneoplastic connective tissue disease or be deficient. Through interdisciplinary biohumoral analyses were carried out contemporarily so as to gain comparative insight into the eventual unfolding of immunological and fibrotic phenomena. The range of the clinical follow-up varied from one to four years with periodic day hospital admissions. We studied ten NF patients that originated from southern Italy and belonged to middle and lower middle class status; we also studied one healthy subject who had the same HLA haplotype as his NF affected twin. We performed biohumoral analyses in clinical stable patients and saw moderate variations in induces useful for monitoring the evolution of this dysplastic-neoplastic condition, e.g. procollagens, interleukin-2, NSE (assayed with radioimmunological methods) and complement these parameters proved to be of use in monitoring the fibrotic evolution of NF. The intent of our work was to complete the earlier studies on NF surveillance, especially during periods of disease evolution and immuno-fibrotic alteration.

Neurofibromatosis evolution is described in relation to the factors that may favour its expansion and immune modifications. NF1 monitorization should employ periodic clinical and immune surveillance. Such an approach would allow the application of immunomodulating treatment (e.g. adapted therapy) only when indicated, thereby reducing its duration and potentiating its efficacy.

Neurofibromatosis, in all its variant forms, is a hereditary disease characterized by dysplasia, neoplasia, and the tendency to expand and undergo malignant transformation. We underline the presence of chronic inflammation and of immunologic interdependency. The immune reactions against the non-self have been investigated histologically in light of the concepts of immunosurveillance and immunotolerance. Such investigations would ameliorate subsequent studies and favour the employment of immunomodulatory treatments.

A multidisciplinary study was performed on cases of neurofibromatosis to highlight the immunological reaction using broad-spectrum hematic tests and multiphase evaluation together with clinical and instrumental monitoring. The aim of the study was to focus attention on this rare disease and prompt further sequential immunological studies. A greater knowledge of the disease would allow the promising potential of new drugs to be exploited, in particular selective immunomodulatory drugs, in the hope of controlling the symptoms of disease (and overcoming further obstacles to the surgical removal of any neurofibromas that the patient wishes.