Polymerase chain reaction (PCR) detection of B cell clonality in Sjögren's syndrome patients: a diagnostic tool of clonal expansion.
Sjögren's syndrome (SS) is an autoimmune disease characterized by clonal B cell attack of the exocrine glands and dysregulated expression of B cell-activating factor (BAFF). Based upon the current data of increased rates of lymphoid malignancy, as non-Hodgkin's lymphoma (NHL) is associated with SS, we propose the detection of clonal rearrangements of immunoglobulin heavy chain (IgH) gene in those patients as a predictor of malignant clonal expansion. To test our proposal, we examined the IgH clonal rearrangements in SS patients (60) and healthy control subjects (42) having chronic non-specific sialadenitis, to determine the presence of clonal B cells in minor labial salivary glands (MSG) of SS patients. Clonal B cell expansion was assessed by two polymerase chain reaction (PCR) assays: (i) semi-nested PCR, against sequences encoding framework regions FR3, FR2 and FR1c of the variable chain IgH gene in B cells present in the MSG infiltrate; and (ii) the PCR-enzyme-linked immunosorbent assay (ELISA) technique, against the major and minor breakpoint regions of the Bcl-2 oncogene coupled with a variable segment of the IgH to assess the Bcl-2/JH translocation. When FR3, FR2 and FR1c primers were employed, we detected B cell monoclonality in 87% of the SS patients and 19% of the control subjects. The association between inflammation severity of the MSG pattern and the presence of B cell clonality was found to be statistically significant (P<0.01). We concluded that the presence of B cell clonality in MSG can be used as a index of an altered microenvironment favouring the development of lymphoma in SS patients.
Guzmán
L M
LM
Laboratorio de Química Biológica, Instituto de Química, Pontificia Universidad Católica de Valparaíso, Santiago, Chile. leda.guzman@ucv.cl
Castillo
D
D
Aguilera
S O
SO
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D019070:Cell Lineage; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics / Q000648:ultrastructure; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics / Q000648:ultrastructure; D002999:Clone Cells / Q000473:pathology*; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D019254:Genes, bcl-2; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D012470:Salivary Glands, Minor / Q000473:pathology; D012680:Sensitivity and Specificity; D012793:Sialadenitis / Q000276:immunology / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology / Q000473:pathology*; D014178:Translocation, Genetic; D055815:Young Adult
D001323:Autoantibodies
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