title: Persistent polyclonal B-cell lymphocytosis: further evidence for a genetic disorder associated with B-cell abnormalities.
abstract: Persistent polyclonal B-cell lymphocytosis (PPBL) is an intriguing disorder diagnosed predominantly in women, usually cigarette smokers, characterized by an increase in the number of polyclonal B lymphocytes. Abnormality of the B-cell population is also evidenced by the presence of multiple bcl-2/Ig gene rearrangements and the finding of an additional long arm chromosome 3q+ (i3)(q10) within a significant proportion of B cells. The physiopathology of PPBL is unknown but its association with the HLA DR7 phenotype suggests a possible genetic disorder. To further determine whether PPBL has a genetic predisposition, we have undertaken an extensive study in a large family of a patient diagnosed with PPBL. Three individuals among the first-degree relatives presented all the criteria for a diagnosis of PPBL. A slight increase in serum IgM without evidence of B-cell proliferation was shown in two additional siblings. Multiple bcl-2/Ig gene rearrangements, a typical feature of PPBL, were identified in 8/10 individuals among first-degree relatives. A statistically significant association was found between the presence of these rearrangements and of a paternal HLA haplotype. We conclude that PPBL has a familial occurrence suggesting an underlying genetic defect. The development of the complete syndrome probably relies on unidentified additional co-factors.
authors.affiliation: Centre d'Hématologie et d'Immunologie Clinique, Hôpital du St-Sacrement, Laval University, 1050 Chemin Ste-Foy, Quebec, Canada. robert.delage@med.ulaval.ca
authors.forename: R
authors.initials: R
authors.lastname: Delage
authors.forename: L
authors.initials: L
authors.lastname: Jacques
authors.forename: M
authors.initials: M
authors.lastname: Massinga-Loembe
authors.forename: J
authors.initials: J
authors.lastname: Poulin
authors.forename: D
authors.initials: D
authors.lastname: Bilodeau
authors.forename: C
authors.initials: C
authors.lastname: Mignault
authors.forename: P F
authors.initials: PF
authors.lastname: Leblond
authors.forename: A
authors.initials: A
authors.lastname: Darveau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002893:Chromosomes, Human, Pair 3; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D019254:Genes, bcl-2; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000032:analysis; D015235:HLA-B Antigens / Q000032:analysis; D059909:HLA-B14 Antigen; D015805:HLA-DR5 Antigen / Q000032:analysis; D006801:Humans; D008218:Lymphocytosis / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D012907:Smoking
chemical_list: D015234:HLA-A Antigens; C037709:HLA-A9 antigen; D015235:HLA-B Antigens; D059909:HLA-B14 Antigen; D015805:HLA-DR5 Antigen