Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) are considered to be related diseases since both can be encountered consecutively in the same patient, they have been described in twins, and bear identical pathological and biological abnormalities. Apart from the presence of extrarenal clinical signs found only in HSPN, other differences are noticed between the two diseases. The peak age ranges between 15 and 30 years for a diagnosis of IgAN, whereas HSPN is mainly seen in childhood. Nephritic and/or nephrotic syndromes are more often seen at presentation in HSPN. In contrast to IgAN, HSPN has been described in association with hypersensitivity. Endocapillary and extracapillary inflammations as well as fibrin deposits in the glomerulus are more frequent in HSPN. No major biological differences have been found between the two illnesses, except for a larger size of circulating IgA-containing complexes (IgA-CC) and a greater incidence of increased plasma IgE levels in HSPN. As tissue infiltration by leukocytes is a major feature of HSPN vasculitis, a possible role of a more potent activation of the latter cells by IgA-CC and/or circulating chemokines in HSPN should be considered. Further studies are required to elucidate this possible mechanism as well as the role of hypersensitivity in HSPN.

Two prototypic types of virus-specific CD8+ T cells can be found in latently infected individuals: CD45R0+CD27+CCR7− effector-memory, and CD45RA+CD27−CCR7− effector-type cells. It has recently been implied that CD45RA+CD27−CCR7− T cells are terminally differentiated effector cells and as such have lost all proliferative capacity. We show in this study, however, that stimulation of CMV-specific CD45RA+CD27−CCR7− T cells with their cognate peptide in concert with either CD4+ help or IL-2, IL-15, or IL-21 in fact induces massive clonal expansion. Concurrently, these stimulated effector T cells change cell surface phenotype from CD45RA to CD45R0 and regain CCR7, while effector functions are maintained. Our data imply that CD45RA+CD27−CCR7− effector-type T cells contribute to immunity not only by direct execution of effector functions, but also by yielding progeny in situations of viral reinfection or reactivation.

Mechanisms underlying the onset and perpetuation of chronic immune activation in individuals without overt infectious or autoimmune diseases are unclear. Cytomegalovirus (CMV) is a persistent virus that induces a permanent increase of highly differentiated, interferon-gamma-secreting effector T cells. We hypothesized that, because of this increase, CMV also induces a systemic inflammatory response. We measured acute phase proteins, cytokines, and chemokines in serum samples from renal transplant recipients who developed a primary CMV infection and healthy CMV serum-positive or -negative individuals. Primary CMV infection induced a clear proinflammatory response that was maintained during latency. This response was characterized by increased levels of acute phase proteins, such as serum amyloid-A and C-reactive protein, and type 1 cytokines, such as interleukin-18, interferon-inducible protein-10, and interferon-gamma. This continuous activation of the immune system may play a role in the pathogenesis of chronic allograft rejection and potentially contribute to the acceleration of chronic diseases.

A single dose of the anti-CD20 monoclonal antibody rituximab induces a nearly complete B cell depletion in peripheral blood, but not in secondary lymphoid organs. Modulation of this remaining B cell population due to rituximab treatment may contribute to the therapeutic effects of rituximab. To assess the in vivo effects of rituximab we used lymph nodes (LNs) collected during renal transplant surgery in patients who had received rituximab 4 weeks earlier in preparation for an ABO-incompatible transplantation. Rituximab treatment resulted in a lower percentage of na € lve (IgD þ CD27 À ) and a higher percentage of switched memory (IgD À CD27 þ ) B cells. Remarkably, transitional (CD24 þþ CD38 þþ ) B cells were virtually lacking in the LNs of rituximab-treated patients. Moreover, LN-derived B cells from rituximab-treated patients produced different amounts of various Ig-subclasses after anti-CD40/IL-21 stimulation ex vivo. Finally, after stimulation of allogeneic T cells with LN-derived B cells from rituximab-treated patients, the proliferated T cells showed a decreased production of IL-17. In conclusion, after treatment with rituximab there remains a B cell population with different functional capacities. Consequently, the effect of rituximab on the immune response will not only be determined by the extent of B cell depletion, but also by the functional properties of the remaining B cells.