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.


METHODS
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.
Jessen
R H
RH
Institute of Pathology, Case Western Reserve University, Cleveland, OH.
Emancipator
S N
SN
Jacobs
G H
GH
Nedrud
J G
JG
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D000956:Antigens, Viral / Q000032:analysis* / Q000502:physiology; D003176:Complement C3 / Q000032:analysis; D004195:Disease Models, Animal; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000276:immunology / Q000382:microbiology*; D006417:Hematuria / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D007109:Immunity / Q000502:physiology; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D015994:Incidence; D007678:Kidney Glomerulus / Q000737:chemistry; D008297:Male; D051379:Mice; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D018184:Paramyxoviridae Infections / Q000150:complications* / Q000276:immunology; D014771:Virion / Q000502:physiology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D003176:Complement C3; D007070:Immunoglobulin A; D007074:Immunoglobulin G