The role of sulfoglucuronosyl glycosphingolipids in the pathogenesis of monoclonal IgM paraproteinemia and peripheral neuropathy

In IgM paraproteinemia and peripheral neuropathy, IgM M-protein secretion by B cells leads to a T helper cell response, suggesting that it is antibody-mediated autoimmune disease involving carbohydrate epitopes in myelin sheaths. An immune response against sulfoglucuronosyl glycosphingolipids (SGGLs) is presumed to participate in demyelination or axonal degeneration in the peripheral nervous system (PNS). SGGLs contain a 3-sulfoglucuronic acid residue that interacts with anti-myelin-associated glycoprotein (MAG) and the monoclonal antibody anti-HNK-1. Immunization of animals with sulfoglucuronosyl paragloboside (SGPG) induced anti-SGPG antibodies and sensory neuropathy, which closely resembles the human disease. These animal models might help to understand the disease mechanism and lead to more specific therapeutic strategies. In an in vitro study, destruction or malfunction of the blood-nerve barrier (BNB) was found, resulting in the leakage of circulating antibodies into the PNS parenchyma, which may be considered as the initial key step for development of disease

IFN-γ primes macrophage responses to bacterial DNA

Macrophages recognize and are activated by unmethylated CpG motifs in bacterial DNA, Here we demonstrate that production of nitric oxide (NO) from murine RAW 264 macrophages and bone marrow-derived macrophages (BMM) in response to bacterial DNA is absolutely dependent on interferon-gamma (IFN-gamma) priming. Similarly, arginine uptake and expression of the inducible nitric oxide synthase (iNOS) gene in response to bacterial DNA in BMM occurred only after IFN-gamma priming, In contrast, mRNA for the cationic amino acid transporter, CAT2, was induced by plasmid DNA alone, and priming with IFN-gamma had no effect on this response. Tumor necrosis factor-alpha (TNF-alpha) release from RAW 264 and BMM in response to bacterial DNA was augmented by IFN-gamma pretreatment, In a stably transfected HIV-1 long terminal repeat (LTR) luciferase RAW 264 cell line, IFN-gamma and bacterial DNA synergized in activation of the HIV-1 LTR. Bacterial DNA has been shown to induce IFN-gamma production in vivo as an indirect consequence of interleukin-12 (IL-12) and TNF-alpha production from macrophages, The results herein suggest the existence of a self-amplifying loop that may have implications for therapeutic applications of bacterial DNA

Pulmonary actinomycosis: a case undergoing resection through video-assisted thoracic surgery (VATS)

Actinomycosis is an uncommon disease, which is usually manifested as cervicofacial infection and related to poor oral hygiene or compromised immune function. Pulmonary actinomycosis is rare, but its diagnosis is changing due to its variable presentation and the similarity in appearance to other intrapulmonary diseases. Here we report an 80-year-old man with a solitary pulmonary nodule over the left upper lobe. Pulmonary neoplasm was highly suspected in this patient and thus resection of the mass was undertaken through video-assisted thoracic surgery (VATS). Histopathological examination demonstrated this patient had an Actinomyeces infection. While the application of VATS in patients with pulmonary actinomycosis has rarely been reported in literature, we conclude that VATS is valuable for the diagnosis and treatment of patients with undetermined pulmonary nodule(s)