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Notes: Summary.  Our objective was to assess the influence of genetic factors such as HLA classes I and II antigens and other clinical and laboratory variables on the progression of HIV disease in a cohort of 118 HIV infected haemophilic subjects of Greek origin who had been typed for HLA antigens and were followed up prospectively for 22 years since seroconversion. At the end of the follow up we compared two groups of patients: 22 patients who had a fast progression to AIDS (median 6 years since seroconversion) vs. 33 patients who remained asymptomatic in stage A2 for up to 22 years (median 15 years). The results showed that the two groups did not differ significantly in age at seroconversion or baseline CD4+ T cell count. However there was a difference in the frequencies of certain HLA antigens in the two groups. The fast progressors had a higher frequency of HLA-A28, B21 and DR3, which was statistically significant (P = 0.02, 0.04, 0.05, respectively) compared to the slow progressors. These findings based on classical HLA typing techniques confirm other published observations and support the effect of genetic background in the progression of HIV infection in haemophilics.

Notes: HIV-related bone marrow changes are consistent with myelodysplastic features (MDF). Their pathogenesis may differ from primary myelodysplastic syndromes (MDS) and is associated with various factors including the virus itself or the antiretroviral therapy. In order to evaluate the differences between HIV-related MDF and MDS, the morphological changes in peripheral blood and bone marrow, cytogenetic analysis and the response to anaemia treatment were studied in 158 HIV+ patients with haemophilia and the results were compared with those of 61 patients with primary MDS (31 with RA, 10 with RARS, 11 with RAEB, three with RAEB-t and six with CMML). The eligibility criteria for patients with MDS were primary MDS, Hb levels 〈 10 g dL–1, and no significant organ disease. The peripheral blood and bone marrow examination revealed MDF in 44 HIV-infected haemophilic patients (27.8%). The median time from seroconversion was 12.5 years and the mean time under AZT therapy was 44.1 months. Nineteen of these patients (43.1%) had Hb levels 〈 10 g dL–1, while neutropenia and thrombocytopenia were observed in 29.5% and 25%, respectively. Every patient of this study with Hb 〈 10 g dL–1 received erythropoietin (Epo). There were statistically significant morphological alterations between HIV-related MDF and MDS: hypocellularity, plasmatocytosis and eosinophilia were more pronounced in HIV haemophiliacs with MDF, while dysplasia of erythroblasts, megakaryocytes and granulocytes was more frequent in MDS patients. No HIV haemophilic patient with MDF had more than 5% blasts in the bone marrow nor did any develop RAEB or acute leukaemia during the period of this study. The cytogenetic analysis was normal in HIV-infected patients with haemophilia whereas 42.6% of patients with MDS had an abnormal karyotype. Complete erythroid response was achieved with Epo administration in 84.2% of HIV+ haemophilic patients with anaemia compared to 19.7% of patients with MDS. These data suggest that bone marrow changes in long-term HIV patients have different characteristics from primary MDS and constitute the entity for which the name HIV-myelopathy has been proposed in the literature.

Notes: Summary Background There is evidence that a T-helper (Th) 2 cytokine pattern dominates in the peripheral blood as well as in tissue of patients with Sézary syndrome (SS), and that the malignant clone is of Th2 phenotype. However, there are conflicting studies on the cytokine pattern in the peripheral blood in different stages of cutaneous T-cell lymphoma (CTCL). Objectives To examine, by means of flow cytometry (FC), the Th1/Th2 cytokine profile [cytoplasmic interferon (IFN)-γ/interleukin (IL)-4] in peripheral blood T cells from patients with mycosis fungoides (MF) and SS, the most common forms of CTCL, and to correlate their expression with clinical stage, clonality and T-cell immunophenotype changes in order to evaluate their relevance in CTCL progression. Methods We investigated by FC the percentage of CD3+ T cells expressing cytoplasmic IFN-γ and IL-4 after stimulation in blood specimens of 43 CTCL patients (32 stage I–II and 11 stage III–IV), eight of whom were erythrodermic. Next, we compared cytoplasmic IFN-γ and IL-4 expression between patients of different stages and controls, and correlated our findings to T-cell receptor (TCR)-γ gene rearrangement, used as a marker of clonality, and changes in T-cell immunophenotype (CD4+, CD8+, CD4+/CD7–, CD4+/CD25+) and natural killer cells. Polymerase chain reaction amplification of the TCR-γ gene was performed in 41 blood and 26 skin specimens. We also examined the cytokine expression pattern in patients with erythrodermic MF and SS. Results A significantly higher frequency of CD3+/IL-4+ T cells was found in late (III–IV) compared with early (I–II) CTCL patients (P = 0·002) or controls (P 〈 0·001). There were significant positive correlations between the percentages of CD3+/IL-4+ and the percentages of CD3+/CD4+ T cells (r = 0·385, P = 0·05), CD4+/CD7– T cells (r = 0·335, P 〈 0·05) and CD4+/CD25+ T cells (r = 0·433, P = 0·01); there was a negative correlation between the percentages of CD3+/IL-4+ and CD3+/CD8+ T cells (r = −0·463, P = 0·005) and a positive correlation between the percentages of CD3+/IFN-γ+ and CD3+/CD8+ T cells (r = 0·368, P = 0·02). Increased percentages of CD3+/IL-4+, CD3+/CD4+ and CD4+/CD7– T lymphocytes were associated with the presence of clonality (P = 0·025, P 〈 0·001 and P = 0·0031, respectively). All independent variables showed a statistically significant difference between SS and erythrodermic MF patients, or controls, apart from cytoplasmic IL-4, which was high both in erythrodermic MF and SS patients compared with controls (P = 0·003 and P = 0·008, respectively). In multiple regression logistic analysis, the probability of belonging to advanced CTCL stages was associated only with increased cytoplasmic IL-4 (P = 0·007, odds ratio 1·13, 95% confidence interval 1·033–1·229). Conclusions Increased T-cell cytoplasmic IL-4 is more frequent in late CTCL stages, correlates with T-cell immunophenotype changes found in advanced disease and is associated with clonality. Increased cytoplasmic IL-4 is frequent both in erythrodermic MF and SS patients, in contrast to other variables found increased only in SS, suggesting that IL-4 may be an early indicator of disease progression. Moreover, our results show that increased cytoplasmic IL-4 is the sole predictor of advanced CTCL disease and confirm the relevance of FC determination of IL-4 in the routine evaluation of CTCL cases.

Notes: Abstract  Flow-cytometric analysis of peripheral blood lymphocytes was performed in 96 patients with chronic idiopathic neutropenia of adults (CINA) and in 36 age- and sex-matched healthy volunteers (controls) using a panel of monoclonal antibodies. Patients were classified arbitrarily into group A (68 patients with 2500–1500 neutrophils/μl) and group B (28 patients with neutrophil counts below 1500/μl). We found that CINA patients displayed low numbers of peripheral blood lymphocytes compared with the controls, which correlated with the numbers of circulating neutrophils. This decrease was due mainly to the reduction of T lymphocytes and, to lesser degree, to the decline of NK cells. Both CD4+ and CD8+ T cells decreased, so that the CD4+/CD8+ cell ratio remained within normal range. Moreover, decrease of T lymphocytes was due essentially to the diminution of CD45RO+ T-cell subsets (CD4+/CD45RO+ and CD8+/CD45RO+), while CD45RA+ T cells did not change. A highly significant positive correlation was found between the numbers of CD45RO+ T cells and the numbers of circulating neutrophils. All these alterations were more pronounced in the patients of group B than in those of group A. NK cells were found to be significantly reduced in the patients of group B, but not in those of group A. The numbers of both CD16+ and CD56+ cells correlated with the numbers of circulating neutrophils. Patients of group B had also low numbers of CD57+ cells, probably due to the reduction of T cells and NK cells. B cells did not change significantly. No significant changes were found also in the numbers of lymphocytes carrying activation-related cell surface markers. We concluded that lymphocyte reduction in CINA patients is due mainly to the diminution of CD45RO+ cells, and we postulated that the most probable explanation for this abnormality is an increased extravasation of these cells, which pass into the tissues following an accelerated adhesion to endothelial cells. This hypothesis and its relationship with the underlying neutropenia in CINA patients remain to be clarified.