Experimental IgA-IgG nephropathy induced by a viral respiratory pathogen. Dependence on antigen form and immune status.

BACKGROUND: The etiology of IgA nephropathy (IgAN), the most common form of glomerulonephritis in the world, remains an enigma. Episodes of nephritis are frequently preceded by acute viral respiratory syndromes, but few experimental models associated with acute viral infection exist. EXPERIMENTAL DESIGN: An animal model of IgAN involving Sendai virus, a rodent parainfluenza virus similar to many human respiratory viruses, is described. Mice were either naturally infected or chronically mucosally immunized with virus. Immunized mice were then challenged intravenously with various physical forms of antigen to simulate viremia or antigenemia secondary to acute viral exposure. Twenty-four hours after challenge of immunized mice or 10 days after natural infection, mice were sacrificed. Anti-viral antibody titers, glomerular immune deposits, and glomerular function were evaluated. RESULTS: Chronic mucosal immunization of mice with Sendai virus resulted in a vigorous serum IgA (and IgG) anti-viral immune response, associated with comparable degrees of IgA, IgG, IgM, and antigen deposits in the glomeruli of both challenged and unchallenged mice. Only immunized, challenged mice developed significant proteinuria and hematuria. Neither deposits nor glomerular dysfunction was seen in controls. The physical form of antigen was important for altered glomerular function; although immunized mice challenged with either live or dead virions had a high incidence of hematuria, mice challenged with purified viral glycoproteins did not, even though all mice exhibited comparable immune deposits. Significant deposits of C3 were not present and were not required for glomerular injury. Finally, naturally infected mice exhibited a milder form of IgAN without hematuria. CONCLUSIONS: The experimental conditions for acute exposure to a natural viral respiratory pathogen of mice leading to IgAN are described. This model may be useful both to probe infection-related IgAN, and to facilitate the understanding of the various mechanisms responsible for IgAN.

Do enzymatic analyses of serum triglycerides really need blanking for free glycerol?

Distributions of concentrations of free glycerol in clinical plasma obtained for triglyceride assay were compiled to determine the frequency with which increased concentrations of free glycerol posed a potential problem for clinical interpretation of triglyceride results. Clinical histories were studied in patients with increased concentrations of free glycerol to ascertain possible reasons for the increase and to assess the relative clinical importance of glycerol-blank-corrected triglyceride results. Significant increases in free glycerol were very uncommon, usually occurring in patients receiving glycerol-containing hyperalimentation fluids, those receiving heparin (which causes both in vivo and in vitro increases in free glycerol), or those critically ill. Free glycerol was never increased significantly in a large outpatient population. Monitoring lipid metabolism in critically ill patients, or measuring true triglyceride concentrations in patients receiving glycerol-containing fluids, may represent rare exceptions for which glycerol-blank correction is necessary for accurate clinical diagnosis and management. We conclude that there is insufficient justification for the routine expenditure of extra time and reagents to correct most analytical enzymatic triglyceride methods for free glycerol.