Paolo Casali

CD5+ B lymphocytes, polyreactive antibodies and the human B-cell repertoire

The lock and key model of antigen-antibody reaction has traditionally been used to explain the specificity of antibodies and the need for antibody diversity. Recently it has become clear that certain antibodies are polyreactive and recognize a variety of self- and foreign antigens. It is now clear that these antibodies are made by a novel subset of B cells that bear the surface CD5 marker. Careful analysis has shown that about 20% of peripheral blood B lymphocytes in adults are CD5+ and, therefore, represent a major component of the normal human B-cell repertoire. The precise role of the antibodies produced by these cells is still not clear, but because of their polyreactivity they might function in clearing autoantigens from the circulation and/or as a rapid first line of defense against foreign invaders, such as bacteria and viruses. Sequence analysis showed that these antibodies use gene segments in germ-line configuration for their antigen-binding portion. In this article, Paolo Casali and Abner Notkins propose that polyreactive antibodies are what, for years, have been referred to as the natural antibodies of serum and that under certain circumstances they may contribute to the pathogenesis of autoimmune diseases.

Prognostic Analysis of Clinicopathologic Factors in 49 Patients With Diffuse Malignant Peritoneal Mesothelioma Treated With Cytoreductive Surgery and Intraperitoneal Hyperthermic Perfusion

BackgroundDiffuse malignant peritoneal mesothelioma (DMPM) is a subset of peritoneal mesothelioma with a poor clinical outcome. We performed a prognostic analysis in a cohort of DMPM patients treated homogeneously by cytoreductive surgery and intraperitoneal hyperthermic perfusion (IPHP).MethodsForty-nine DMPM patients who underwent 52 consecutive procedures were enrolled onto the study. Cytoreductive surgery was performed according to the peritonectomy technique, and the IPHP was performed with cisplatin plus doxorubicin or cisplatin plus mitomycin C. We assessed the correlation of the clinicopathologic variables (previous surgical score, age, sex, performance status, previous systemic chemotherapy, carcinomatosis extension, completeness of cytoreduction, IPHP drug schedule, mitotic count [MC], nuclear grade, and biological markers [epidermal growth factor receptor, p16, matrix metalloproteinase 2 and matrix metalloproteinase 9]) with overall and progression-free survival.ResultsThe mean age was 52 years (range, 22–74 years). The mean follow-up was 20.3 months (range, 1–89 months). Regarding the biological markers, the rates of immunoreactivity of epidermal growth factor receptor, p16, matrix metalloproteinase 2, and matrix metalloproteinase 9 were 94%, 60%, 100%, and 85%, respectively. The strongest factors influencing overall survival were completeness of cytoreduction and MC, whereas those for progression-free survival were performance status and MC. No biological markers were shown to be of prognostic value.ConclusionsCompleteness of cytoreduction, performance status, and MC seem to be the best determinants of outcome. These data warrant confirmation by a further prospective formal trial. No biological markers presented a significant correlation with the outcome. The overexpression of epidermal growth factor receptor, matrix metalloproteinase 2, and matrix metalloproteinase 9 and absent or reduced expression of p16 might be related to the underlining tumor kinetics of DMPM and warrant further investigation with other methods.

Characterization of Multireactive Autoantibodies and Identification of LEU-1+ B Lymphocytes as Cells Making Antibodies Binding Multiple Self and Exogenous Molecules

(1988). Characterization of Multireactive Autoantibodies and Identification of LEU-1+ B Lymphocytes as Cells Making Antibodies Binding Multiple Self and Exogenous Molecules. International Reviews of Immunology: Vol. 3, No. 1-2, pp. 17-45.

Immunosuppression by Measles Virus

The ability of measles virus to alter an expected immune (adaptive) response was first recognized by Clements von Pirquet in 1908. He observed that chil dren who were tuberculin positive before contracting acute measles virus infection failed to mount specific skin responses to tuberculin during measles. Later reports confirmed von Pirquet–s observation and extended his findings to other infectious agents.(1–8) Furthermore, during acute measles virus infection, humans may not make antibodies to tetanus toxoid or H and O antigens of Salmonella typhi. Lymphocytes harvested from persons undergoing acute measles virus infection respond poorly, in vitro, to a variety of mitogenic or antigenic stimuli and are deficient in producing chemotactic factors. Therefore, in vivo infection with measles virus can result in a weakened or abolished immune response and in susceptibility to concurrent infection with other viral or bacterial agents.(9,10–16) Indeed, it has been recognized that during measles virus infection, susceptibility to herpes simplex virus (HSV) increases(17) and pulmonary tuberculosis worsens(18–20) By contrast, lipoid nephrosis, a disease that frequently responds to immune suppressive therapy, can dramatically improve in the presence of a concomitant measles virus infection(21–23) The concept that measles virus can also impair the function of some cells involved in natural defense (nonadaptive) mechanisms stems from more recent findings and suggests the need for wider reconsideration of the in vivo immunosuppressive role of measles virus.(24)

The Use of the Epstein-Barr Virus to Probe the Human B Cell Repertoire and to Generate Monoclonal Antibodies

Most studies on the interaction of viruses with the host have been concerned with the analysis of disease pathogenesis and forms of treatment. It is now becoming clear that viruses also can serve as powerful tools to explore cellular functions or as vectors to carry genetic information for the expression of a variety of biological and clinically important products. In this minireview, we summarize how the Epstein-Barr virus (EBV) is being used to probe the human B lymphocyte repertoire and to make human monoclonal antibodies.