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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2004-6-24
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pubmed:abstractText |
Lymphocyte infiltration of salivary and lacrimal glands leading to diminished secretion and gland destruction as a result of apoptosis is thought to be pivotal in the pathogenesis of Sjögren's syndrome (SS). The cytoskeletal protein alpha-fodrin is cleaved during this apoptotic process, and a strong antibody (Ab) response is elicited to a 120-kd fragment of cleaved alpha-fodrin in the majority of SS patients, but generally not in other diseases in which apoptosis also occurs. Little is known about the anti-alpha-fodrin autoantibody response on a molecular level. To address this issue, IgG phage display libraries were generated from the bone marrow of two SS donors and a panel of anti-alpha-fodrin IgGs was isolated by selection on alpha-fodrin immunoblots. All of the human monoclonal Abs (hmAbs) reacted with a 150-kd fragment and not with the 120-kd fragment or intact alpha-fodrin, indicating that the epitope recognized became exposed after alpha-fodrin cleavage. Analysis of a large panel of SS patients (defined by the strict San Diego diagnostic criteria) showed that 25% of SS sera exhibited this 150-kd alpha-fodrin specificity. The hmAbs stained human cultured salivary acinar cells and the staining was redistributed to surface blebs during apoptosis. They also stained inflamed acinar/ductal epithelial cells in SS salivary tissue biopsies, and only partially co-localized with monoclonal Abs recognizing the full-length alpha-fodrin. Our study shows that in SS patients, neoepitopes on the 150-kd cleaved product of alpha-fodrin become exposed to the immune system, frequently eliciting anti-150-kd alpha-fodrin Abs in addition to the previously reported anti-120-kd Abs. The anti-150-kd alpha-fodrin hmAbs may serve as valuable reagents for the study of SS pathogenesis and diagnostic analyses of SS salivary gland tissue.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-10328193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-10364354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-10393849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-11093442,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-11327263,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-11490512,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-11665980,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-12097413,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-12108543,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-12108757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-14528510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-1719545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-1826052,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-2257875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-2440339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-2558824,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-2647727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-3821573,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-3892303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-7511686,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-8016418,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-8466861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-8712861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-8798976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-8910516,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-8920967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-8940103,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-9008604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-9110981,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-9624143,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/15215161-9856838
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0002-9440
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
165
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
53-61
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15215161-Humans,
pubmed-meshheading:15215161-Animals,
pubmed-meshheading:15215161-Mice,
pubmed-meshheading:15215161-Biopsy,
pubmed-meshheading:15215161-Salivary Glands,
pubmed-meshheading:15215161-Sjogren's Syndrome,
pubmed-meshheading:15215161-Molecular Weight,
pubmed-meshheading:15215161-Epitopes,
pubmed-meshheading:15215161-Cells, Cultured,
pubmed-meshheading:15215161-Autoantibodies,
pubmed-meshheading:15215161-Sensitivity and Specificity,
pubmed-meshheading:15215161-Subcellular Fractions,
pubmed-meshheading:15215161-Immunoglobulin G,
pubmed-meshheading:15215161-Carrier Proteins,
pubmed-meshheading:15215161-Sequence Analysis, DNA,
pubmed-meshheading:15215161-Antibodies, Monoclonal,
pubmed-meshheading:15215161-Apoptosis,
pubmed-meshheading:15215161-Microfilament Proteins,
pubmed-meshheading:15215161-Tumor Necrosis Factor-alpha,
pubmed-meshheading:15215161-Blotting, Western,
pubmed-meshheading:15215161-Microscopy, Confocal,
pubmed-meshheading:15215161-Peptide Library
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