Lp25 membrane protein from pathogenic Leptospira spp. is associated with rhabdomyolysis and oliguric acute kidney injury in a guinea pig model of leptospirosis.

Acute kidney injury (AKI) from leptospirosis is frequently nonoliguric with hypo- or normokalemia. Higher serum potassium levels are observed in non-survivor patients and may have been caused by more severe AKI, metabolic disarrangement, or rhabdomyolysis. An association between the creatine phosphokinase (CPK) level and maximum serum creatinine level has been observed in these patients, which suggests that rhabdomyolysis contributes to severe AKI and hyperkalemia. LipL32 and Lp25 are conserved proteins in pathogenic strains of Leptospira spp., but these proteins have no known function. This study evaluated the effect of these proteins on renal function in guinea pigs. Lp25 is an outer membrane protein that appears responsible for the development of oliguric AKI associated with hyperkalemia induced by rhabdomyolysis (e.g., elevated CPK, uric acid and serum phosphate). This study is the first characterization of a leptospiral outer membrane protein that is associated with severe manifestations of leptospirosis. Therapeutic methods to attenuate this protein and inhibit rhabdomyolysis-induced AKI could protect animals and patients from severe forms of this disease and decrease mortality.

Lp25 membrane protein from pathogenic Leptospira spp. is associated with rhabdomyolysis and oliguric acute kidney injury in a guinea pig model of leptospirosis

Acute kidney injury (AKI) from leptospirosis is frequently nonoliguric with hypo- or normokalemia. Higher serum potassium levels are observed in non-survivor patients and may have been caused by more severe AKI, metabolic disarrangement, or rhabdomyolysis. An association between the creatine phosphokinase (CPK) level and maximum serum creatinine level has been observed in these patients, which suggests that rhabdomyolysis contributes to severe AKI and hyperkalemia. LipL32 and Lp25 are conserved proteins in pathogenic strains of Leptospira spp., but these proteins have no known function. This study evaluated the effect of these proteins on renal function in guinea pigs. Lp25 is an outer membrane protein that appears responsible for the development of oliguric AKI associated with hyperkalemia induced by rhabdomyolysis (e.g., elevated CPK, uric acid and serum phosphate). This study is the first characterization of a leptospiral outer membrane protein that is associated with severe manifestations of leptospirosis. Therapeutic methods to attenuate this protein and inhibit rhabdomyolysis-induced AKI could protect animals and patients from severe forms of this disease and decrease mortality.

Immunohistochemical and in situ hybridization studies of the liver and kidney in human leptospirosis.

An in situ hybridization (ISH) assay for the detection of leptospiral DNA in tissues was described and its diagnostic and pathogenetic usefulness in combination with immunohistochemistry (IHC) was evaluated in formalin-fixed, paraffin-embedded liver and kidney samples from human fatal cases of leptospirosis. IHC assays with anti-E-cadherin antibodies assessed the liver-plate disarray frequently observed in leptospirosis. Immunohistochemistry detected leptospiral antigen (LAg) in macrophages, both in human liver and kidney. In guinea pigs, in addition to these findings, staining on cell membranes of hepatocytes and, occasionally, in apical membrane of kidney tubular cells was demonstrated. Positive ISH signal was observed chiefly in the nuclei of human hepatocytes and in the cytoplasm and nuclei of liver cells of experimentally infected guinea pigs. Loss of E-cadherin membrane expression is associated with liver-plate disarray. These findings were discussed in the contention that, in leptospirosis, cell membrane damage might be important for the pathogenesis of the disease. Finally, it was suggested that both IHC and/or ISH might be used for both diagnostic and research purposes.

Antigen distribution and antigen-presenting cells in skin biopsies of human chromoblastomycosis.

BACKGROUND: Chromoblastomycosis is a chronic, suppurative, granulomatous mycosis usually confined to skin and subcutaneous tissues. The host defense mechanisms in chromoblastomycosis have not been extensively investigated. The purpose of the present study was to determine the distribution and pathways of the fungal antigen(s) and the possible role of the different immunocompetent cells in antigen processing in skin lesions. METHODS: The distribution of Fonsecaea pedrosoi antigen(s) in human skin was studied in 18 biopsies from 14 patients with chromoblastomycosis. A purified polyclonal immune serum raised in rabbits against metabolic antigen(s) of F. pedrosoi was used to detect yeast antigen(s) by immunohistochemical procedures. Double immunolabeling was performed with yeast antigen(s) and Langerhans' cells [labeled with anti-S100 protein monoclonal antibody (MoAb)], yeast antigen(s) and factor XIIIa+ dermal dendrocytes (immunolabeled with anti-factor XIIIa polyclonal antibody), and yeast antigen(s) and macrophages (labeled with CD 68 monoclonal antibody). RESULTS: The F. pedrosoi antigen(s) accumulated in the skin macrophages and, in a few instances, in factor XIIIa+ dendrocytes and Langerhans' cells. CONCLUSIONS: The data obtained suggest that chiefly macrophages, also Langerhans' cells and factor XIIIa+ dermal dendrocytes, function as antigen-presenting cells in chromoblastomycosis.