Implications of modifying cardiolipin acyl composition by diet. 1. Cardiolipin acyl chain is an important determinant in the binding to antiphospholipid antibodies in SLE sera

Alvin Berger, J. Bruce German, M. Eric Gershwin

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Abstract

Antiphospholipid antibodies (aPL), prevalent in sera of patients with systemic lupus erythematosus (SLE), have been linked to thrombosis, thrombocytopenia, recurrent miscarriages, neurological disorders and ischemic heart disease. Most evidence suggests that phosphodiester-linked phosphate groups are the reactive epitope of cardiolipin (CL) in binding to aPL. Little attention has been given to the acyl moiety. To address this problem we have evaluated the ELISA binding of 12 highly positive IgG anticardiolipin antibody-positive SLE sera to: bovine CL (86.1% 18:2n-6), monolyso CL (MLCL; bovine CL minus 1 fatty acid), dilyso CL (DLCL; minus 2 fatty acids), tetraoleoyl CL (TOCL), myristoyl CL (MCL) and E. coli CL. The reductions in binding of the IgG aPL antibodies relative to bovine CL were as follows: DLCL 83%; MLCL 70.7%; MCL 58%; and TOCL 14% (P<0.05). These data suggest that the number of acyl chains and the unsaturation of the acyl chain of CL may be important determinants in the binding to aPL present in SLE sera. To investigate the nutritional relevance of this finding, we examined the incorporation of several dietary fatty acid classes into the CL pool of mice. Mice were fed diets containing n-6 (safflower oil), n-9 (olive oil) or n-3 fatty acids as either 18:3n-3 (linseed oil) or 20:5n-3/22:6n-3 (fish oil) for a 5 month period. The feeding of fish oil and olive oil resulted in replacement of a substantial portion of 18:2n-6 with 22:6n-3 or 18:1n-9, respectively. These results suggest that there may be therapeutic value in modifying the CL acyl composition by nutritional means with respect to binding to pathogenic aPL.

Original languageEnglish (US)
Pages (from-to)229-241
Number of pages13
JournalJournal of Autoimmunity
Volume5
Issue number2
DOIs
StatePublished - 1992

Fingerprint

Antiphospholipid Antibodies
Cardiolipins
Systemic Lupus Erythematosus
Diet
Serum
Fatty Acids
Fish Oils
Immunoglobulin G
Linseed Oil
Safflower Oil
Anticardiolipin Antibodies
Habitual Abortion
Omega-3 Fatty Acids
Nervous System Diseases
Thrombocytopenia
Myocardial Ischemia
Epitopes
Thrombosis
Enzyme-Linked Immunosorbent Assay
Phosphates

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

@article{68cd71d2475a4d4792891d66977816a2,
title = "Implications of modifying cardiolipin acyl composition by diet. 1. Cardiolipin acyl chain is an important determinant in the binding to antiphospholipid antibodies in SLE sera",
abstract = "Antiphospholipid antibodies (aPL), prevalent in sera of patients with systemic lupus erythematosus (SLE), have been linked to thrombosis, thrombocytopenia, recurrent miscarriages, neurological disorders and ischemic heart disease. Most evidence suggests that phosphodiester-linked phosphate groups are the reactive epitope of cardiolipin (CL) in binding to aPL. Little attention has been given to the acyl moiety. To address this problem we have evaluated the ELISA binding of 12 highly positive IgG anticardiolipin antibody-positive SLE sera to: bovine CL (86.1{\%} 18:2n-6), monolyso CL (MLCL; bovine CL minus 1 fatty acid), dilyso CL (DLCL; minus 2 fatty acids), tetraoleoyl CL (TOCL), myristoyl CL (MCL) and E. coli CL. The reductions in binding of the IgG aPL antibodies relative to bovine CL were as follows: DLCL 83{\%}; MLCL 70.7{\%}; MCL 58{\%}; and TOCL 14{\%} (P<0.05). These data suggest that the number of acyl chains and the unsaturation of the acyl chain of CL may be important determinants in the binding to aPL present in SLE sera. To investigate the nutritional relevance of this finding, we examined the incorporation of several dietary fatty acid classes into the CL pool of mice. Mice were fed diets containing n-6 (safflower oil), n-9 (olive oil) or n-3 fatty acids as either 18:3n-3 (linseed oil) or 20:5n-3/22:6n-3 (fish oil) for a 5 month period. The feeding of fish oil and olive oil resulted in replacement of a substantial portion of 18:2n-6 with 22:6n-3 or 18:1n-9, respectively. These results suggest that there may be therapeutic value in modifying the CL acyl composition by nutritional means with respect to binding to pathogenic aPL.",
author = "Alvin Berger and German, {J. Bruce} and Gershwin, {M. Eric}",
year = "1992",
doi = "10.1016/0896-8411(92)90202-2",
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pages = "229--241",
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T1 - Implications of modifying cardiolipin acyl composition by diet. 1. Cardiolipin acyl chain is an important determinant in the binding to antiphospholipid antibodies in SLE sera

AU - Berger, Alvin

AU - German, J. Bruce

AU - Gershwin, M. Eric

PY - 1992

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N2 - Antiphospholipid antibodies (aPL), prevalent in sera of patients with systemic lupus erythematosus (SLE), have been linked to thrombosis, thrombocytopenia, recurrent miscarriages, neurological disorders and ischemic heart disease. Most evidence suggests that phosphodiester-linked phosphate groups are the reactive epitope of cardiolipin (CL) in binding to aPL. Little attention has been given to the acyl moiety. To address this problem we have evaluated the ELISA binding of 12 highly positive IgG anticardiolipin antibody-positive SLE sera to: bovine CL (86.1% 18:2n-6), monolyso CL (MLCL; bovine CL minus 1 fatty acid), dilyso CL (DLCL; minus 2 fatty acids), tetraoleoyl CL (TOCL), myristoyl CL (MCL) and E. coli CL. The reductions in binding of the IgG aPL antibodies relative to bovine CL were as follows: DLCL 83%; MLCL 70.7%; MCL 58%; and TOCL 14% (P<0.05). These data suggest that the number of acyl chains and the unsaturation of the acyl chain of CL may be important determinants in the binding to aPL present in SLE sera. To investigate the nutritional relevance of this finding, we examined the incorporation of several dietary fatty acid classes into the CL pool of mice. Mice were fed diets containing n-6 (safflower oil), n-9 (olive oil) or n-3 fatty acids as either 18:3n-3 (linseed oil) or 20:5n-3/22:6n-3 (fish oil) for a 5 month period. The feeding of fish oil and olive oil resulted in replacement of a substantial portion of 18:2n-6 with 22:6n-3 or 18:1n-9, respectively. These results suggest that there may be therapeutic value in modifying the CL acyl composition by nutritional means with respect to binding to pathogenic aPL.

AB - Antiphospholipid antibodies (aPL), prevalent in sera of patients with systemic lupus erythematosus (SLE), have been linked to thrombosis, thrombocytopenia, recurrent miscarriages, neurological disorders and ischemic heart disease. Most evidence suggests that phosphodiester-linked phosphate groups are the reactive epitope of cardiolipin (CL) in binding to aPL. Little attention has been given to the acyl moiety. To address this problem we have evaluated the ELISA binding of 12 highly positive IgG anticardiolipin antibody-positive SLE sera to: bovine CL (86.1% 18:2n-6), monolyso CL (MLCL; bovine CL minus 1 fatty acid), dilyso CL (DLCL; minus 2 fatty acids), tetraoleoyl CL (TOCL), myristoyl CL (MCL) and E. coli CL. The reductions in binding of the IgG aPL antibodies relative to bovine CL were as follows: DLCL 83%; MLCL 70.7%; MCL 58%; and TOCL 14% (P<0.05). These data suggest that the number of acyl chains and the unsaturation of the acyl chain of CL may be important determinants in the binding to aPL present in SLE sera. To investigate the nutritional relevance of this finding, we examined the incorporation of several dietary fatty acid classes into the CL pool of mice. Mice were fed diets containing n-6 (safflower oil), n-9 (olive oil) or n-3 fatty acids as either 18:3n-3 (linseed oil) or 20:5n-3/22:6n-3 (fish oil) for a 5 month period. The feeding of fish oil and olive oil resulted in replacement of a substantial portion of 18:2n-6 with 22:6n-3 or 18:1n-9, respectively. These results suggest that there may be therapeutic value in modifying the CL acyl composition by nutritional means with respect to binding to pathogenic aPL.

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