Monoclonal gammopathy of renal significance (MGRS) histopathologic classification, diagnostic workup, and therapeutic options.

Monoclonal gammopathy of renal significance (MGRS) includes all kidney disorders caused by a monoclonal protein (M-protein) secreted by a small plasma cell clone or other B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. The underlying disorder in patients with MGRS is generally consistent with monoclonal gammopathy of undetermined significance (MGUS). MGRS-associated kidney disorders are various and the list is still expanding. The kidney disorders can manifest as glomerular diseases, tubulopathies, and vascular involvement with varying clinical presentations. Diagnosis is often challenging because of the wide spectrum of MGRS, and it is difficult to establish a pathogenic link between the presence of the M-protein or serum free light chains and kidney diseases; further complicating accurate diagnosis is the high incidence of MGUS and/or kidney disorders, independent of MGRS, in elderly patients. However, MGRS can significantly impair kidney function. Because treatment can stop and also reverse kidney disease, early recognition is of great importance. A combined haematologic and nephrologic approach is crucial to establish the causative role of the M-protein in the pathogenesis of kidney disease. Clone-directed therapy, which may include autologous stem cell transplantation in eligible patients, often results in improved outcomes. In this review, we discuss the histopathologic classification of MGRS lesions, provide a renal and haematologic diagnostic workup, discuss treatment options for MGRS, and introduce a Benelux MGRS Working Group.

Preparation and investigation of P28GST-loaded PLGA microparticles for immunomodulation of experimental colitis.

The aim of this work was to prepare and characterize (in vitro and in vivo) PLGA-based microparticles loaded with an enzymatic protein derived from the helminth parasite Schistosoma haematobium: glutathione S-transferase P28GST (P28GST). This protein is not only a promising candidate vaccine against schistosomiasis, it also exhibits interesting immunomodulating effects, which can be helpful for the regulation of inflammatory diseases. Helminths express a regulatory role on intestinal inflammation, and immunization by P28GST has recently been shown to be as efficient as infection to reduce inflammation in a murine colitis model. As an alternative to the combination with a classical adjuvant, long acting P28GST microparticles were prepared in order to induce colitis prevention. PLGA was used as biodegradable and biocompatible matrix former, and a W/O/W emulsion/solvent extraction technique applied to prepare different types of microparticles. The effects of key formulation and processing parameters (e.g., the polymer molecular weight, drug loading, W/O/W phase volumes and stirring rates of the primary/secondary emulsions) on the systems' performance were studied. Microparticles providing about constant P28GST release during several weeks were selected and their effects in an experimental model of colitis evaluated. Mice received P28GST-loaded or P28GST-free PLGA microparticles (s.c.) on Day 0, and optionally also on Days 14 and 28. Colitis was induced on Day 35, the animals were sacrificed on Day 37. Interestingly, the Wallace score (being a measure of the severity of the inflammation) was significantly lower in mice treated with P28GST microparticles compared to placebo after 1 or 3 injections. As immunogenicity markers, increased anti-P28GST IgG levels were detected after three P28GST PLGA microparticle injections, but not in the control groups. Thus, the proposed microparticles offer an interesting potential for the preventive treatment of experimental colitis, while the underlying mechanism of action is still to be investigated.

Periodontal manifestations of inflammatory bowel disease: emerging epidemiologic and biologic evidence.

Inflammatory bowel disease and periodontitis are both described as a disproportionate mucosal inflammatory response to a microbial environment in susceptible patients. Moreover, these two conditions share major environmental and lifestyle-related risk factors. Despite this intriguing pathogenic parallel, large-scale studies and basic research have only recently considered periodontal outcomes as relevant data. There are mounting and consistent arguments, from recent epidemiologic studies and animal models, that these two conditions might be related. This article is a comprehensive and critical up-to-date review of the current evidence and future prospects in understanding the biologic and epidemiologic relationships between periodontal status and inflammatory bowel disease.

The schistosome glutathione S-transferase P28GST, a unique helminth protein, prevents intestinal inflammation in experimental colitis through a Th2-type response with mucosal eosinophils.

Intestinal helminth parasites are potent inducers of T helper type 2 (Th2) response and have a regulatory role, notably on intestinal inflammation. As infection with schistosomes is unlikely to provide a reliable treatment of inflammatory bowel diseases, we have investigated the beneficial effect of a schistosome enzymatic protein, the 28-kDa glutathione S-transferase (P28GST), on the modulation of disease activity and immune responses in experimental colitis. Our results showed that immunization with recombinant P28GST is at least as efficient as established schistosome infection to reduce colitis lesions and expression of pro-inflammatory cytokines. Considering underlying mechanisms, the decrease of inflammatory parameters was associated with the polarization of the immune system toward a Th2 profile, with local and systemic increases of interleukin (IL)-13 and IL-5. Dense eosinophil infiltration was observed in the colons of P28GST-immunized rats and mice. Depletion of eosinophils by treatment with an anti-Siglec-F monoclonal antibody and use of IL-5-deficient mice led to the loss of therapeutic effect, suggesting the crucial role for eosinophils in colitis prevention by P28GST. These findings reveal that immunization with P28GST, a unique recombinant schistosome enzyme, ameliorates intestinal inflammation through eosinophil-dependent modulation of harmful type 1 responses, representing a new immuno-regulatory strategy against inflammatory bowel diseases.

Autoimmune haemolytic anaemia associated with a thymoma: case report and review of the literature.

A 67-year-old female presents with a small mass in the anterior mediastinum on chest computed tomography. A biopsy proves the mass to be a spindle-cell-type or type A thymoma. Subsequently the patient develops fever and severe Coombs-positive haemolytic anaemia. She is initially treated with oral corticosteroids. Because of persistence of the haemolysis subsequent thymectomy is performed. Haemolysis disappears almost instantly and does not return after discontinuation of the oral corticosteroids. Review of the literature reveals only 17 other cases of thymoma-associated autoimmune haemolytic anaemia.

Electrical injuries to peripheral nerves.

As people come frequently into contact with electrical power sources, electrical injuries to peripheral nerves are commonly seen. The authors first review the parameters determining the severity and distribution of electrical injury to nerve tissue. These include tissue resistance, tissue susceptibility, current pathway, type of current, current density, duration and size of electrical contact. Subsequently, the pathophysiology of electrical injuries to nerve tissue is reviewed. Such injuries can be the result of thermal damage, vascular impairment, histological or electrophysiological changes in peripheral nerves, or direct mechanical trauma. Each of these types of injuries causes, specific lesions. As these lesions, especially delayed peripheral neurologic injury, can cause medico-legal problems, it is important to emphasize that electroneuromyography must be performed as early as possible.