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Home > Archive > Lupus Support > September 2005 > Systemic lupus erythematosus / oxidative stress
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Systemic lupus erythematosus / oxidative stress
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| ironjustice@aol.com 2005-09-24, 2:37 pm |
| <<snip>>
These data may suggest a hitherto unappreciated mechanism by which
oxidative stress facilitates epitope spreading in SLE
<<snip>>
Free Radical Biology and Medicine
Volume 38, Issue 6 , 15 March 2005, Pages 719-728
doi:10.1016/j.freeradbiomed.2004.11.001
Copyright =A9 2004 Elsevier Inc. All rights reserved.
Original Contribution
Modification of lupus-associated 60-kDa Ro protein with the lipid
oxidation product 4-hydroxy-2-nonenal increases antigenicity and
facilitates epitope spreading
R=2E Hal Scofielda, b, c, , , Biji T. Kuriena, Samantha Ganicka, Micah T.
McClaina, b, Quentin Pyed, Judith A. Jamesa, b, Rebecca I. Schneidera,
Robert H. Broylesd, Michael Bachmanna and Kenneth Hensleyd, e
aArthritis and Immunology Program, Oklahoma Medical Research
Foundation, Oklahoma City, OK 73104, USA
bDepartment of Medicine, university of Oklahoma Health Sciences Center,
Oklahoma City, OK 73104, USA
cDepartment of Veterans Affairs Medical Center, Oklahoma City, OK
73104, USA
dFree Radical Biology and Aging Research Program, Oklahoma Medical
Research Foundation, Oklahoma City, OK 73104, USA
eOklahoma Center for Neuroscience and Department of Cell Biology,
University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104,
USA
Received 22 March 2004; revised 4 September 2004; accepted 1 November
2004. Available online 31 December 2004.
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with
autoantibodies as a near universal feature of the disease. The Ro
ribonucleoprotein particle, composed of a 60-kDa protein noncovalently
associated with human cytoplasmic RNA, is the target of antibodies in
25-40% of lupus patients. Purified human 60-kDa Ro was found to be
oxidatively modified. Earlier investigations from our laboratory
revealed increased oxidative damage in SLE patients. Therefore we
hypothesized that oxidation by-products, such as 4-hydroxy-2-nonenal
(HNE), could lead to neoantigens like HNE-modified 60-kDa Ro, which
could in turn initiate autoimmunity or drive epitope spreading. To test
this hypothesis we immunized rabbits with either HNE-modified 60-kDa Ro
or the unmodified Ro. Intramolecular epitope spreading within the Ro
molecule and intermolecular epitope spreading to La, double-stranded
DNA, nRNP, and Sm occurred preferentially in HNE-Ro-immunized
animals. Nonspecific anti-HNE antibody, generated by immunization with
HNE-keyhole limpet hemocyanin conjugate, did not significantly bind
to these autoantigens. These data may suggest a hitherto unappreciated
mechanism by which oxidative stress facilitates epitope spreading in
SLE.
Keywords: Free radicals; Lupus; Autoimmunity; Epitopes; Autoantibodies;
Antigens; Hydroxynonenal
Corresponding author. Fax: +1 (405) 271 4110.
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com
Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
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| lehill1 2005-09-24, 2:37 pm |
| OK - so what does this mean in "real people" terms??????
<ironjustice@aol.com> wrote in message
news:1126144043.832188.140140@g49g2000cwa.googlegroups.com...
<<snip>>
These data may suggest a hitherto unappreciated mechanism by which
oxidative stress facilitates epitope spreading in SLE
<<snip>>
Free Radical Biology and Medicine
Volume 38, Issue 6 , 15 March 2005, Pages 719-728
doi:10.1016/j.freeradbiomed.2004.11.001
Copyright © 2004 Elsevier Inc. All rights reserved.
Original Contribution
Modification of lupus-associated 60-kDa Ro protein with the lipid
oxidation product 4-hydroxy-2-nonenal increases antigenicity and
facilitates epitope spreading
R. Hal Scofielda, b, c, , , Biji T. Kuriena, Samantha Ganicka, Micah T.
McClaina, b, Quentin Pyed, Judith A. Jamesa, b, Rebecca I. Schneidera,
Robert H. Broylesd, Michael Bachmanna and Kenneth Hensleyd, e
aArthritis and Immunology Program, Oklahoma Medical Research
Foundation, Oklahoma City, OK 73104, USA
bDepartment of Medicine, university of Oklahoma Health Sciences Center,
Oklahoma City, OK 73104, USA
cDepartment of Veterans Affairs Medical Center, Oklahoma City, OK
73104, USA
dFree Radical Biology and Aging Research Program, Oklahoma Medical
Research Foundation, Oklahoma City, OK 73104, USA
eOklahoma Center for Neuroscience and Department of Cell Biology,
University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104,
USA
Received 22 March 2004; revised 4 September 2004; accepted 1 November
2004. Available online 31 December 2004.
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with
autoantibodies as a near universal feature of the disease. The Ro
ribonucleoprotein particle, composed of a 60-kDa protein noncovalently
associated with human cytoplasmic RNA, is the target of antibodies in
25-40% of lupus patients. Purified human 60-kDa Ro was found to be
oxidatively modified. Earlier investigations from our laboratory
revealed increased oxidative damage in SLE patients. Therefore we
hypothesized that oxidation by-products, such as 4-hydroxy-2-nonenal
(HNE), could lead to neoantigens like HNE-modified 60-kDa Ro, which
could in turn initiate autoimmunity or drive epitope spreading. To test
this hypothesis we immunized rabbits with either HNE-modified 60-kDa Ro
or the unmodified Ro. Intramolecular epitope spreading within the Ro
molecule and intermolecular epitope spreading to La, double-stranded
DNA, nRNP, and Sm occurred preferentially in HNE-Ro-immunized
animals. Nonspecific anti-HNE antibody, generated by immunization with
HNE-keyhole limpet hemocyanin conjugate, did not significantly bind
to these autoantigens. These data may suggest a hitherto unappreciated
mechanism by which oxidative stress facilitates epitope spreading in
SLE.
Keywords: Free radicals; Lupus; Autoimmunity; Epitopes; Autoantibodies;
Antigens; Hydroxynonenal
Corresponding author. Fax: +1 (405) 271 4110.
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com
Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
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