The anti-IRBP IgG1 and IgG2a response does not correlate with susceptibility to experimental autoimmune uveitis.
Susceptibility to experimental autoimmune uveitis (EAU) in inbred mice has been associated with a dominant Th1 response. Elevated anti-inter-photoreceptor retinoid-binding protein (anti-IRBP) IgG2a/IgG1 antibody ratios have been implicated as candidate markers to predict disease severity. In the present study, both the anti-IRBP antibody isotype and severity of EAU phenotypes were examined in 4 non-isogenic genetically selected mouse lines to determine if they can be used as general markers of disease. Mice between 8 and 12 weeks old selected for high (H(III)) or low (L(III)) antibody response and for maximum (AIR(MAX)) or minimum (AIR(MIN)) acute inflammatory reaction (AIR) were immunized with IRBP. Each experiment was performed with at least 5 mice per group. EAU was evaluated by histopathology 21 days after immunization and the minimal criterion was inflammatory cell infiltration of the ciliary body, choroid and retina. Serum IgG1- and IgG2a-specific antibodies were determined by ELISA. EAU was graded by histological examination of the enucleated eyes. The incidence of EAU was lower in AIR(MIN) mice whereas in the other strains approximately 40% of the animals developed the disease. Low responder animals did not produce anti-IRBP IgG2a antibodies or interferon-gamma. No correlation was observed between susceptibility to EAU and anti-IRBP isotype profiles. Susceptibility to EAU is related to the intrinsic capacity to mount higher inflammatory reactions and increased production of anti-IRBP IgG2a isotype is not necessarily a marker of this immunologic profile.
de Moraes
L Vieira
LV
Laboratório de Imunologia Clínica, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
Martins
G A
GA
Flangini
M
M
Ibañez
O M
OM
Sant'Anna
O A
OA
Rizzo
L V
LV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015415:Biomarkers; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D008822:Mice, Transgenic; D012177:Retinol-Binding Proteins / Q000276:immunology*; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014605:Uveitis / Q000276:immunology* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D005136:Eye Proteins; D007074:Immunoglobulin G; D007371:Interferon-gamma; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial