Abstract
Sjögren's syndrome (SS) is a systemic autoimmune disorder with a strong tumor predisposition (a 44-fold elevated incidence of non-Hodgkin's lymphoma has been reported). By polymerase chain reaction analysis of t(14;18), a key lymphomagenic event in peripheral blood lymphocytes, we found a lower frequency in a subset of 12 SS patients positive for SS-A/SS-B autoantibodies than in 21 healthy subjects and 20 SS patients lacking these SS marker autoantibodies (P < 0.001). All 14 mutants sequenced displayed signs typical of V(D)J recombinase activity. This perplexing result of a low rate of t(14;18) in a population strongly predisposed to t(14;18)-associated tumor development may be explained by a constitutive deficiency in V(D)J recombinase leading to autoimmunity and increased lymphoproliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Antinuclear / analysis
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Autoimmune Diseases / genetics*
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Autoimmunity / genetics
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B-Lymphocytes / enzymology
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B-Lymphocytes / pathology*
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Base Sequence
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Chromosomes, Human, Pair 14 / genetics
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Chromosomes, Human, Pair 14 / ultrastructure*
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Chromosomes, Human, Pair 18 / genetics
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Chromosomes, Human, Pair 18 / ultrastructure*
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DNA Nucleotidyltransferases / deficiency
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Genes, Immunoglobulin
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Genes, bcl-2
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Genetic Predisposition to Disease
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Humans
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Immunoglobulin Heavy Chains / genetics
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Lymphoma, Non-Hodgkin / genetics*
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Molecular Sequence Data
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Polymerase Chain Reaction
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Sjogren's Syndrome / genetics*
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Translocation, Genetic*
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VDJ Recombinases
Substances
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Antibodies, Antinuclear
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Immunoglobulin Heavy Chains
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DNA Nucleotidyltransferases
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VDJ Recombinases