Sjögren's syndrome: lymphoma predisposition coupled with a reduced frequency of t(14;18) translocations in blood lymphocytes.
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.
Henriksson
G
G
Department of Medical Microbiology, University Hospital, Malmö, Sweden.
Brant
M
M
Sandor
Z
Z
Manthorpe
R
R
Bredberg
A
A
D000974:Antibodies, Antinuclear / Q000032:analysis; D001327:Autoimmune Diseases / Q000235:genetics*; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000201:enzymology / Q000473:pathology*; D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics / Q000648:ultrastructure*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics / Q000648:ultrastructure*; D004254:DNA Nucleotidyltransferases / Q000172:deficiency; D005803:Genes, Immunoglobulin; D019254:Genes, bcl-2; D020022:Genetic Predisposition to Disease; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000235:genetics*; D014178:Translocation, Genetic; D045567:VDJ Recombinases
D000974:Antibodies, Antinuclear; D007143:Immunoglobulin Heavy Chains; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases