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We previously reported that susceptibility to childhood B cell precursor ALL (BCP ALL) is associated with HLA-DPB1 alleles having glutamic acid (E) rather than lysine (K) in the P4 antigenic peptide-binding pocket. Clustering ∼90% of DPB1 alleles into DPB69E (DP2, 6, 8) and DPB69K (DP1, 3, 4) supertypes revealed that DP2 and DP8 are associated with BCP ALL, but DP6 is also associated with non-BCP leukaemia. Here, we report that only one of seven alleles with the DP6 supertype (DPB1*0601) is associated with childhood leukaemia (leukaemia vs controls: odds ratio, 95% confidence interval [OR, CI]: 4.6, 2.0–10.4; corrected P=0.019), but not with childhood solid tumours or lymphomas. DPB1*0601 is also significantly associated with leukaemia subtypes, including BCP ALL, Pro-B ALL, T-ALL and AML. DPB1*0601 is significantly over-transmitted (76.9%) from parents to children with BCP ALL (OR; CI: 4.7; 1.01–22.2). Sequencing the coding region of DPB1*0601 revealed an exon 1–4 haplotype [T-DEAV-KIL-RVI] shared with DPB1*0301 and 0901, but no evidence of germline mutations in childhood leukaemia. These results suggest that the DPβ0601 molecule may be functionally involved in childhood leukaemia. Analysis of peptide binding and T-cell activation by DPβ0601-peptide complexes should help determine its role in childhood leukaemia causation.Leukemia (2009) 23, 863–869; doi:10.1038/leu.2008.374; published online 15 January 2009 [ABSTRACT FROM AUTHOR]

Autologous acute myeloid leukaemia (AML) cells caused the suppression of incorporation of ³H-thymine (³H-Tdr) by remission lymphocytes stimulated with allogeneic cells. In five patients, autologous .AMI, cells suppressed ³H-Tdr uptake by lymphocytes stimulated with up to three different allogeneic cells. Responses to allogeneic AMI, cells were more strongly suppressed than responses to pooled allogeneic lymphocytes. Suppression was abolished by ultrasonic disintegration of the autologous AMI, cells, suggesting that a soluble factor was not involved. Suppression was absent from autologous AML cells exposed to ultraviolet light, or when untreated autologous AML cells were present in ratios of < 1 : 1 to lymphocytes, or when added 24 or more hours after stimulation of remission lymphocytes with allogeneic cells. It is suggested that suppression is a property of the differentiative level of AML cells, rather than of their malignant properties, although malignant-transformation may bring A.ML cells into contact with circulating of cells in vivo. Autologous AML cells seem to interferes with the recognition phase of T cell function. [ABSTRACT FROM AUTHOR]

Monosomy 21 (M21) is a rare aneuploid condition which in certain cases leads to reduced levels of chromosome 21 gene products. We have prepared an Epstein Barr virus lymphoblastoid cell-line (LCL) from patient with M21 who has immunological abnormalities, and analysed the expression of lymphocyte function-associated antigen-1 (LFA-1), This heterodimeric leucocyte integrin consists of CD11a (α) subunits non-covalently associated with CD18 (β) subunits coded, respectively, by genes on chromosomes 16 and 21. To determine whether monosomy 21 results in decreased expression of LFA-1, monoclonal antibodies were used to compare the expression of CD11a and CD18 on the M21 LCL with LCL from trisomy 21 (Down's syndrome, T21), normal controls and a possible case of leucocyte adhesion deficiency. In addition, phorbol-ester-induced homotypic adhesion, an LFA-1-mediated effect, was compared in these LCLs. The results are consistent with a gene dosage mediated reduction of LFA-1 expression by the M21 LCL. [ABSTRACT FROM AUTHOR]

The monoclonal antibody (MAB) 60-3 reacts with the β chain (CD18) of lymphocyte function associated antigen (LFA-1), encoded by a gene on chromosome 21. We have used 603 to measure the expression of CDIK on lymphoblastoid cell-lines derived from persons with Trisomy 21 (Down syndrome) by quantitative fluorescence flow cylometric analysis. This showed that CD 18 expression is increased on Trisomy 21 compared with normal cells, whereas neither HLA-class I. nor transferrin receptor expression are significantly affected. Similar results were obtained with the CDl 8 MAB MHM 23, and with the CDl la MAB MHM 24 (LFA-1α). These results suggest that the increase in CD 18 expression by Trisomy 21 cells is due to gene dosage, and could influence the immune status of persons with Down syndrome. [ABSTRACT FROM AUTHOR]

We describe a family in which two sisters with the autosomal dominant skeletal dysplasia, Leri-Weill dyschondrosteosis (LWD), developed Hodgkin's disease (HD) in late adolescence. In a preliminary attempt to identify HD susceptibility gene(s), HLA-typing and linkage analysis were carried out in the family. Using HLA molecular typing, both sisters were found to have inherited a variant of the HD-susceptibility allele, DPB1*0301, known as DPB1*2001. Following a previous report of a constitutional chromosome translocation (t(2q;8p)) in a family with LWD, preliminary linkage studies were carried out using chromosome 2q and 8p molecular markers. Regions covered by 7/10 chromosome 2 markers and 4/8 chromosome 8 markers were excluded as the location of a candidate LWD gene. Given the rarity of LWD and HD, their simultaneous occurrence is unlikely to have been due to chance. We suggest that a mutation in the LWD gene itself, or a gene closely linked to it, perhaps acting with increased susceptibility to infection conferred by DPB1*2001, resulted in HD in the two sisters.

The monoclonal antibody (MAB) 60.3 reacts with the beta chain (CD18) of lymphocyte function associated antigen (LFA-1), encoded by a gene on chromosome 21. We have used 60.3 to measure the expression of CD18 on lymphoblastoid cell-lines derived from persons with Trisomy 21 (Down syndrome) by quantitative fluorescence flow cytometric analysis. This showed that CD18 expression is increased on Trisomy 21 compared with normal cells, whereas neither HLA-class I, nor transferrin receptor expression are significantly affected. Similar results were obtained with the CD18 MAB MHM 23, and with the CD11a MAB MHM 24 (LFA-1 alpha). These results suggest that the increase in CD18 expression by Trisomy 21 cells is due to gene dosage, and could influence the immune status of persons with Down syndrome.

Autologous acute myeloid leukaemia (AML), cells caused the suppression of incorporation of 3H-thymidine (3H-Tdr) by remission lymphocytes stimulated with allogeneic cells. In five patients, autologous AML cells suppressed 3H-Tdr uptake by lymphocytes stimulated with up to three different allogeneic cells. Responses to allogeneic AML cells were more strongly suppressed than responses to pooled allogeneic lymphocytes. Suppression was abolished by ultrasonic disintegration of the autologous AML cells, suggesting that a soluble factor was not involved. Suppression was absent from autologous AML cells exposed to ultraviolet light, or when untreated autologous AML cells were present in ratios of less than 1:1 to lymphocytes, or when added 24 or more hours after stimulation of remission lymphocytes with allogeneic cells. It is suggested that suppression is a property of the differentiative level of AML cells, rather than of their malignant properties, although malignant-transformation may bring AML cells into contact with circulating T cells in vivo. Autologous AML cells seem to interfere with the recognition phase of T cell function.