Springer Seminars in Immunopathology

IgA nephropathy is a frequent disease, reported in almost every country in the world, which appears early in the life of males rather than females. It is readily diagnosed by immunofluorescence analysis of a renal biopsy. Its benign reputation begins to fade as more cases of rapid evolution towards renal failure are reported. Much has been learned about the various forms of IgAN in the past 15 years, yet complete understanding of the disease mechanism eludes us. Many clinicians and immunologists, however, continue the investigation, which will hopefully soon bring more complete answers and good news for the patients.

Programmed cell death and the disposal of cell corpses by phagocytic cells are highly regulated ongoing processes essential for the survival and well-being of higher organisms. Abnormalities in the susceptibility of certain cells to receptor-induced death are known to lead to certain human diseases (e.g., autoimmune lymphoproliferative syndrome) and may contribute to the pathogenesis of systemic lupus erythematosus. Impaired clearance of apoptotic cells is also likely to be an important factor in lupus pathogenesis, though the biological basis of such a defect remains elusive. Finally, the process of apoptosis has been shown to contribute to lupus disease effector mechanisms. A better understanding of the role of apoptosis in lupus very likely will lead to improved diagnosis and therapy.

HSCT in autoimmune diseases has now become one of the potential therapeutic options for physicians looking after patients with severe intractable autoimmune diseases. It has now progressed beyond theory based on animal and human case reports, but at this stage it has been appropriately reserved for patients with resistant disease in a clinical trial setting. Ongoing analysis of the safety and efficacy of patients in phase I/II trials will allow us to determine if there is a wider role for the procedure in diseases such as RA, SLE, SSc and MS. Meta-analyses of the data will enable appropriate selection of patients and the optimal transplant procedure, so that eventually randomised trials against gold standard therapy will become a reality. In the future, with a decreased morbidity and mortality from allogeneic transplantation, cure of these diseases is not an unrealistic option.

The multivalency of cold-reactive IgM anti-lymphocyte autoantibodies, together with the local density of reactive antigens on the cell surface, may confer a capacity for a variety of immunoregulatory and non-specific physiological roles in the immune system and in SLE and other autoimmune diseases. Targets of interest in this regard include CD45, β 2 microglobulin, and surface immunoglobulin. IgG anti-lymphocyte autoantibodies, while more difficult to study, also exhibit interesting specificities. However, whether any of the mechanisms by which anti-lymphocyte autoantibodies could alter cellular function actually obtain in vivo remains speculative. Essentially all of the data in this regard derive from experiments in which anti-lymphocyte autoantibody-containing SLE serum or plasma, or purified Ig fractions thereof, is combined with peripheral blood mononuclear cells in short-term culture in vitro. Thus, it is possible that anti-lymphocyte autoantibodies in SLE, rather than contributing to pathogenesis, reflect a physiological attempt by the immune system to restore homeostasis in the face of aggressive autoimmune stimulation.

This review of clinical and morphologic features of PBC deals with four processes in the evolution of the disease: (1) etiologic and predisposing features; (2) injury of bile ducts and secondarily of hepatocytes; (3) precholestasis and cholestasis; and (4) hepatic derangement not of a biliary nature. It further refers to four stages in the evolution of PBC — ductal, ductular, scarring, and cirrhotic stage — with extensive transitions between each other and recurrence of previous stages in later ones. Probably a different immunologic process is responsible for the initial and continuing bile duct injury and for a secondary “hepatitic” component as well as for the periductular fibrosis. The further evolution of PBC, however, appears to be dominated by the cholestatic consequences of mechanical fibrotic interference with biliary secretion, mainly in the periportal area. Assisted by progression of the “ hepatitic” process, it results to varying degrees in destruction of the hepatic architecture, potentially terminating in cirrhosis. But PBC is not a primary cholestatic disease; frank cholestasis is clinically and histologically a relatively late phenomenon in a disease still mysterious and with a potentially long evolution. Cirrhosis, which is the conventional name of the disease, is only present or even in development during a short terminal fraction of the total life span of the disease. Although PBC is a relatively rare disease, even if now more readily recognized, it nevertheless serves as a useful experiment of nature for clarifying the pathology of liver disease in general and its immunologic aspects in particular.

This review highlights some of the most common cytokines currently being tested as adjuvants in HIV-1-DNA vaccine regimens. We discuss their use in both the prophylactic and therapeutic setting. Finally, we describe a novel dendritic cell-targeted vaccine candidate for HIV-1 treatment and prevention called DermaVir and explore the combination of the DermaVir technology with the cytokine adjuvants interleukin-7 and interleukin-15.