Antinuclear antibody titer and antibodies to extractable nuclear antigens

The development of glomerulonephritis in NZB/W mice is closely related to the formation of antinuclear, particularly anti-DNA, antibodies. The developing inflammatory glomerular lesions are characterized by the deposition of γG- and ß1C-globulins plus DNA and possibly other nuclear antigens, presumably as complexes, in a granular to lumpy pattern along the capillary walls and in the mesangia. Elution studies revealed the γG-globulin in the glomeruli to be largely γG2A-type antibody to soluble nuclear antigens. Enhancement of the antinuclear antibody response by active immunization of young NZB/W mice with DNA-methylated BSA hastens the development and increases the severity of the glomerulonephritis. Similarly, injections of soluble DNA into NZB/W mice with circulating anti-DNA antibodies but with as yet little nephritis causes rapid progression of nephritis.

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PATHOGENESIS OF IMMUNE COMPLEX GLOMERULONEPHRITIS OF NEW ZEALAND MICE

Journal of Experimental Medicine ◽

10.1084/jem.134.3.65 ◽

1971 ◽

Vol 134 (3) ◽

pp. 65-71 ◽

Cited By ~ 86

Author(s):

Frank J. Dixon ◽

Michael B. A. Oldstone ◽

Giorgio Tonietti

Keyword(s):

New Zealand ◽

Immune Complex ◽

Antibody Formation ◽

Antinuclear Antibody ◽

Viral Infections ◽

Antibody Responses ◽

Viral Antigens ◽

Chronic Viral Infections ◽

Nuclear Antigens ◽

Antigen Antibody

Observations based on elution of IgG from nephritic kidneys of NZ mice and absorption of the eluted IgG with selected antigens indicate that their immune complex nephritis involves at least two kinds of antigen-antibody complexes. Antibodies reactive with nuclear antigens account for nearly half of the IgG eluted from the kidneys while antibodies reactive with Gross viral antigens make up a significant but lesser amount. Superimposed chronic viral infections affect the nephritis of NZ mice in different ways. LCM and polyoma infections hasten and intensify the antinuclear antibody responses and glomerulonephritis of these mice while LDV infection appears to protect against both antinuclear antibody formation and development of nephritis.

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Breaking Tolerance to Double Stranded DNA, Nucleosome, and Other Nuclear Antigens Is Not Required for the Pathogenesis of Lupus Glomerulonephritis

Journal of Experimental Medicine ◽

10.1084/jem.20031519 ◽

2004 ◽

Vol 199 (2) ◽

pp. 255-264 ◽

Cited By ~ 130

Author(s):

Samuel T. Waters ◽

Marcia McDuffie ◽

Harini Bagavant ◽

Umesh S. Deshmukh ◽

Felicia Gaskin ◽

...

Keyword(s):

Lupus Erythematosus ◽

Antinuclear Antibody ◽

Early Mortality ◽

Chromosome 1 ◽

Chronic Glomerulonephritis ◽

Chromosome 4 ◽

Double Stranded Dna ◽

Nuclear Antigens ◽

Dsdna Antibody ◽

Lupus Glomerulonephritis

In lupus-prone NZM2328 mice, a locus Cgnz1 on chromosome 1 was linked to chronic glomerulonephritis, severe proteinuria, and early mortality in females. A locus Adnz1 on chromosome 4 was linked to antinuclear antibody (ANA) and anti–double stranded DNA (dsDNA) antibody (Ab) production. In this investigation, two congenic strains, NZM2328.C57L/Jc1 (NZM.C57Lc1) and NZM2328.C57L/Jc4 (NZM.C57Lc4), were generated by replacing the respective genetic intervals containing either Cgnz1 or Adnz1 with those from C57L/J, a nonlupus-prone strain. The NZM.C57Lc1 females had markedly reduced incidence of chronic glomerulonephritis and severe proteinuria. NZM.C57Lc4 females had chronic glomerulonephritis and severe proteinuria without circulating ANA, anti-dsDNA, and antinucleosome Ab. These data confirm the linkage analysis. Unexpectedly, NZM.C57Lc1 females had little anti-dsDNA and related Ab, suggesting the presence of a second locus Adnz2 on chromosome 1. The diseased NZM.C57Lc4 kidneys had immune complexes by immunofluorescence and electron microscopy. The eluates from these kidneys did not contain ANA, anti-dsDNA, and antinucleosome Ab, indicative of the presence of non–anti-dsDNA nephritogenic Ab. Thus, breaking tolerance to dsDNA and chromatin is not required for the pathogenesis of lupus nephritis. These results reaffirm that anti-dsDNA and related Ab production and chronic glomerulonephritis are under independent genetic control. These findings have significant implications in the pathogenesis of systemic lupus erythematosus.

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