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Lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the clonal proliferation of large granular lymphocytes of either T- or natural killer cell origin. To better understand the nature of T cell-type LDGL, we purified the CD4-CD8+ proliferative fractions from LDGL patients (n=4) and the surface marker-matched T cells isolated from healthy volunteers (n=4), and compared the expression profiles of 3456 genes using DNA microarray. Through this analysis, we identified a total of six genes whose expression was active in the LDGL T cells, but silent in the normal ones. Interestingly, expression of the gene for interleukin (IL) 1beta was specific to LDGL T cells, which was further confirmed by the examination of the serum level of IL-1beta protein. Given its important role in inflammatory reactions, the disease-specific expression of IL-1beta may have a causative relationship with the LDGL-associated rheumatoid arthritis. Spectratyping analysis of the T-cell receptor repertoire also proved the monoclonal or oligoclonal nature of LDGL cells. These data have shown that microarray analysis with a purified T-cell subset is an efficient approach to investigate the pathological condition of Tcell-type LDGL.

The clonal proliferation of large granular lymphocytes can be detected in patients with T-cell-lineage granular lymphocyte-proliferative disorders (T-GLPD) by Southern blotting T-cell receptor genes. However, this cannot be applied to patients with natural killer-cell-lineage GLPD (NK-GLPD) as it lacks a clonal marker. We therefore investigated the use of two other diagnostic techniques in evaluating clonal proliferation in Japanese patients with NK-GLPD (n = 4) and T-GLPD (n = 3) by chromosomal analysis of peripheral blood mononuclear cells (PBMC) stimulated with either interleukin-2 or phytohaemagglutinin, and Epstein-Barr viral (EBV) genomic DNA analysis. Chromosomal analysis revealed abnormal karyotypes in the PBMC of three of four patients with NK-GLPD, whereas EBV analysis showed a monoclonal terminal configuration in the PBMC in the fourth patient. Southern blots revealed rearrangements of the TCR genes in all three patients with T-GLPD but in none of those with NK-GLPD. It is suggested that these methods may be useful in detecting the abnormal proliferation of large granular lymphocytes in NK-GLPD.

The −5 C/T polymorphism of platelet glycoprotein (GP) Ibα is a major determinant of the level of GP Ib/V/IX complex surface expression. We investigated the frequency of this polymorphism among Asian populations. The gene frequencies of cytosine (C) in this polymorphism were 0·283 and 0·219 in Japanese and Korean populations respectively. The C allele is linked with human platelet antigen (HPA)-2a and smaller types of variable number of tandem repeats (VNTR). A novel allele, C-HPA-2a-D of VNTR, was found. No association was observed between these alleles and coronary artery disease in this case–control study. The clinical relevance of this polymorphism in the thrombotic status remains undetermined.

We describe a patient with eosinophilia and an abnormal CD3 + 4 - 8 - αβ + T-cell population. Chromosomal analysis of sorted CD3 + 4 - 8 - cells revealed abnormal karyotypes on chromosome 16. In the presence of IL-2 the production of IL-5 from CD3 + 4 - 8 - cells was higher than that from CD3 + 4 + /8 + cells. Eosinophil survival-enhancing activity in the patient serum was inhibited by a combination of anti-IL-5 and anti-GM-CSF monoclonal antibodies. These data suggest that increased production of IL-5 and GM-CSF from the abnormal CD3 + 4 - 8 - cells might cause eosinophilia.

Lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the clonal proliferation of large granular lymphocytes of either T- or natural killer cell origin. To better understand the nature of T cell-type LDGL, we purified the CD4-CD8+ proliferative fractions from LDGL patients (n=4) and the surface marker-matched T cells isolated from healthy volunteers (n=4), and compared the expression profiles of 3456 genes using DNA microarray. Through this analysis, we identified a total of six genes whose expression was active in the LDGL T cells, but silent in the normal ones. Interestingly, expression of the gene for interleukin (IL) 1beta was specific to LDGL T cells, which was further confirmed by the examination of the serum level of IL-1beta protein. Given its important role in inflammatory reactions, the disease-specific expression of IL-1beta may have a causative relationship with the LDGL-associated rheumatoid arthritis. Spectratyping analysis of the T-cell receptor repertoire also proved the monoclonal or oligoclonal nature of LDGL cells. These data have shown that microarray analysis with a purified T-cell subset is an efficient approach to investigate the pathological condition of Tcell-type LDGL.

The -5 C/T polymorphism of platelet glycoprotein (GP) Ib alpha is a major determinant of the level of GP Ib/V/IX complex surface expression. We investigated the frequency of this polymorphism among Asian populations. The gene frequencies of cytosine (C) in this polymorphism were 0.283 and 0.219 in Japanese and Korean populations respectively. The C allele is linked with human platelet antigen (HPA)-2a and smaller types of variable number of tandem repeats (VNTR). A novel allele, C-HPA-2a-D of VNTR, was found. No association was observed between these alleles and coronary artery disease in this case-control study. The clinical relevance of this polymorphism in the thrombotic status remains undetermined.