Degree of modification of Ro60 by the lipid peroxidation by-product 4-hydroxy-2-nonenal may differentially induce Sjögren syndrome or systemic lupus erythematosus in BALB/c mice.
Our previous work showed that immunization of rabbits with 4-hydroxy-2-nonenal-modified Ro60 (HNE-Ro60) accelerates autoimmunity. We extended this model into mice, hypothesizing that the severity of autoimmunity would be dependent on the degree of HNE modification of Ro60. Five groups of BALB/c mice (10/group) were used. Group I was immunized with Ro60. Groups II to IV were immunized with Ro60 modified with 0.4 mM (low), 2 mM (medium), and 10 mM (high) HNE, respectively. Group V controls received Freund's adjuvant. A rapid abrogation of tolerance to Ro60/La antigens occurred in mice immunized with HNE-modified Ro60, especially in the low and medium HNE-Ro60 groups. Lymphocytic infiltration and significantly high decrement in salivary flow (37%) compared to controls was observed only in the high HNE-Ro60 group, suggesting induction of a Sjögren syndrome-like condition in this group. Anti-dsDNA occurred only in mice immunized with medium HNE-Ro60. This group did not have a significant decrement in salivary flow, suggesting induction of a systemic lupus erythematosus-like manifestation in this group. Significantly high antibodies to Ro60 were found in saliva of mice in the low and medium HNE-Ro60 and the Ro60 groups, as well as anti-HNE Ro60 in the low and medium HNE-Ro60 groups. Understanding the mechanism of this differential induction may help discriminate between these two autoimmune diseases.
Kurien
Biji T
BT
Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Porter
Andrew
A
Dorri
Yaser
Y
Iqbal
Saqib
S
D'Souza
Anil
A
Singh
Anil
A
Asfa
Sima
S
Cartellieri
Marc
M
Mathias
Kristen
K
Matsumoto
Hiroyuki
H
Bachmann
Michael
M
Hensley
Kenneth
K
Scofield
R Hal
RH
D000447:Aldehydes / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D005260:Female; D015227:Lipid Peroxidation; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012261:Ribonucleoproteins / Q000276:immunology* / Q000378:metabolism*; D012469:Salivary Glands / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000503:physiopathology; D000099207:SS-A Antigen
D000447:Aldehydes; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C027576:4-hydroxy-2-nonenal