[Neurofibromatosis (NF1) and neuroleprosy: immunoreaction against pathologic Schwann-cells. Physiopathogenetic observations]. / Neurofibromatosi (NF1) e neurolebbra: immunoreazione verso cellule di Schwann patologiche. Considerazioni fisiopatogenetiche.

BACKGROUND: We reviewed the literature evaluating the immune reaction in neurofibromatosis (NF1) and neuroleprosy, so as to underline the immunopathegenetic parallelism and the possible therapeutic implications regarding the treatment of these two disorders. In particular we evaluated the systemic modifications and the local fibrotic events that lead to nerve damage in NF1 and complete neuronal destruction as in leprosy. METHODS: With the above aim in mind we studied the histology, histochemistry and immunohistochemistry (Schwann cells and immunoglobulins) of four plexiform neurofibroma, one common neurofibroma and one case of borderline neuroleprosy (BT). RESULTS: Two plexiform neurofibromas showed an evident immune reaction that was antibody mediated with numerous IgG; the remaining neurofibromas represented other stages of disease evolution and disease quiescence and thus showed a scarce immune reaction with a reduced presence of immunoglobulins. All the neurofibromas showed the presence of fibrous bundles. In the case of neuroleprosy (BT), the immune reaction was modest, immunoglobulins were present and fibrotic transformation on neuronal fibers was observed. CONCLUSIONS: Being that pathologic Schwann cell are the site of immune reactions that can become abnormal (at times with autoimmune reactions), clinical as well as biochemical surveillance of leprous neuropathy and NF1 could allow for a timely modification of the abnormal reaction with selective immunomodulators. The inactivation of the mycobacterial RNA polymerase or of the NF1 gene could offer hope for controlling disease activity and disease evolution of the two disorders.

Tumour suppressor genes, immunology and local manifestations of neurofibromatosis phenotypes.

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.

Hepatitis C virus genotypes, hepatitis, and hepatitis C virus recurrence after liver transplantation.

Several genotypes of hepatitis C virus (HCV) have been recently identified by phylogenetic analysis, but their clinical relevance in the liver transplant setting is unknown. We evaluated the incidence and course of recurrent hepatitis C after transplantation in 50 patients who underwent transplantation for HCV-related liver disease. Liver biopsy specimens were obtained when clinically indicated and at yearly intervals; hepatitis was histologically graded and staged according to standard criteria. HCV-RNA was detected by nested reverse-transcription polymerase chain reaction (RT-PCR). HCV genotyping was performed by primer specific PCR. Follow-up was 6 to 62 months. HCV genotype distribution after transplantation of our 50 patients was as follows: 31 type 1b, 13 type 2a, 3 type 1a, 1 type 3a, 1 type 1b/2a, and 1, undetermined. Actuarial rates of recurrent hepatitis and of severe fibrosis or cirrhosis 5 years after transplantation were 56% and 20%, respectively, in patients infected by type 1b and 33% (P = .18) and 8% (P = .16) in those infected by 2a. In conclusion, this study provides evidence that in patients infected by HCV type 1b there is a trend for a more aggressive recurrent liver disease.

[The clinico-immunological surveillance of neurofibromatosis]. / La sorveglianza clinico-immunologica delle neurofibromatosi.

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.

Immunological and clinical surveillance in Recklinghausen's neurofibromatosis (NF1).

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.

[Local immune response in neurofibromatosis type 1 and type 2]. / L'immunoreazione locale nelle neurofibromatosi di von Recklinghausen e del neurinoma bilaterale del nervo acustico.

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.

[Immune reaction in von Recklinghausen's neurofibromatosis]. / La reazione immunitaria nelle neurofibromatosi di von Recklinghausen.

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.

[Clinico-diagnostic significance of the determination of bile acids in chronic liver diseases]. / Significato clinico-diagnostico del dosaggio di alcuni acidi biliari sierici nelle epatopatie croniche.

Certain conjugated biliary acids (total pool - choliglycine - sulpholytic choliglycine) and the following haematochemical parameters: total bilirubin and its direct quota, alkaline phosphatase, albumin, prothrombin activity, gamma globulin, oxalacetic and pyruvic transaminase were radioimmunologically (RIA) studied in 115 subjects. Subjects were divided into the following subgroups: --20 normal controls; --20 cases of persistent chronic hepatitis; --20 cases of active chronic hepatitis; --15 cases of A.C.H. with cirrhosis; --20 cases of cirrhosis without direct hyperbilirubinaemia; --20 cases of cirrhosis with direct hyperbilirubinaemia. Each case was assigned to its particular group on the basis of the histological report on each patient. The following observations were drawn from the results obtained: --there is a progressive increase in above normal biliary acid rate in proportion to the gravity of the liver pathology; --choliglycine especially and to a lesser extent the total pool increased sufficiently to distinguish between normal and hepatopathic subjects (PCH and ACH) and also between PCH and ACH patients; --the combination of cirrhosis and ACH causes a significant increase in total pool and chliglycine over levels noted in ACH alone; --in contrast no difference is found between the levels of these acids in inactive (or minimally active) cirrhosis and ACH with cirrhosis; --gamma globulin, oxalacetic and pyruvic transaminase levels were found to have substantially the same diagnostic significance as choliglycine in the early stages of liver diseases. Significant correlations were also encountered between total conjugated biliary acid pool and choliglycine (not in the group with cirrhosis without direct hyperbilirubinaemia) and between total pool and choliglycine with haematochemical cholestasis test results (alkaline phosphatase and total and direct bilirubin) the latter only in the two cirrhotics groups. In conclusion, choliglycine was found to be the most sensitive of the biliary acids routinely measured by RIA and is valuable in clinical practice not as a substitute for the main liver tests but as an extremely useful and sensitive addition to them. In clinical practice, its use is recommended in the diagnosis and monitoring of healthy subjects at risk and those with chronic liver conditions (PCH, ACH, ACH + C).