title: Class II human leucocyte antigen DRB1*11 in hairy cell leukaemia patients with and without haemolytic uraemic syndrome.
abstract: Frequencies of human leucocyte antigens (HLA) were determined in 287 classic hairy cell leukaemia (HCL) patients. With respect to both population (n = 287) and allele (2n = 574) frequency respectively, the most common HLA class I and II antigens expressed were HLA-A*02 (49·1% and 28·6%), HLA-B*07 (21·3% and 11·1%), HLA-C*07 (46·7 and 28·2%), HLA-DQB1*03 (62·7% and 37·3%), HLA-DRB1*11 (30·0% and 16·0%) and HLA-DRB4*01 (45·3% and 29·6%). In comparing 6-14 databases of control Caucasians to 267 Caucasian HCL patients, only HLA-DRB1*11 was consistently over-represented in HCL, 31·1% of patients vs. 17-19·9% of controls (P = 0·0055 to <0·0001) and 16·5% of alleles vs. 6·5-12·3% of control alleles (P = 0·022 to <0·0001). HLA-DRB1*11 is a known risk factor for acquired thrombotic microangiopathy. Anti-CD22 recombinant immunotoxin BL22 in HCL was associated with a 12% incidence of completely reversible grade 3-4 haemolytic uraemic syndrome (HUS), mainly during the second or third retreatment cycle. Of 49 HCL patients receiving ≥2 cycles of BL22, 7 (14%) had HUS and HLA-DRB1*11 was expressed in 71% of 7 with HUS compared with only 21% of 42 without (P = 0·015). These data suggest that DBR1*11 may be a marker for increased susceptibility to HCL and, among HCL patients, could be a risk factor for BL22-induced HUS.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Arons
authors.forename: Sharon
authors.initials: S
authors.lastname: Adams
authors.forename: David J
authors.initials: DJ
authors.lastname: Venzon
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001427:Bacterial Toxins / Q000627:therapeutic use; D005098:Exotoxins / Q000627:therapeutic use; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics* / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D057049:Thrombotic Microangiopathies; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D059811:HLA-DRB1 Chains; C508422:HLA-DRB1*11 antigen; C541974:immunotoxin HA22
keywords: ADAMTS13; HLA-DQB1*03; moxetumomab pasudotox; recombinant immunotoxin; thrombotic microangiopathy