F cells, fetal hemoglobin levels, lymphocyte subsets, and frequency of crises in sickle-cell disease in Kuwait.

In vitro, fetal hemoglobin (Hb F) inhibits the aggregation of Hb S, and this may be clinically significant. Alterations in B and T lymphocytes seen in sickle-cell disease may be important in the immune deficit in these patients. We examined 16 patients with repeated crises (6 females and 10 males, age 9.3 +/- 3.4 years) and 15 patients with infrequent crises (9 females and 6 males, age 7.1 +/- 3.8 years) to determine the relationship between F cells, Hb F levels, lymphocyte subsets, and the frequency of crises. The proportion of CD2 and CD3 lymphocytes was significantly lower (P=0.015 and <0.0001, respectively) in both groups of patients than controls. CD4 lymphocytes were significantly lower (P = 0.018) and CD19 significantly higher (P = 0.007) than controls. CD45RO levels in both groups of patients were comparable with matched controls but significantly lower (P = 0.002) than adult values. Hb F levels in patients with and without frequent crises were comparable (P = 0.067). However, F cells in patients with infrequent crises were significantly higher than in patients with frequent crises (P<0.01). Alteration in the lymphocyte subsets did not correlate with the frequency of crisis in these patients.

Abnormal lymphocyte subsets in Kuwaiti patients with type-1 insulin-dependent diabetes mellitus and their first-degree relatives.

Circulating lymphocyte subset imbalance is associated with type-1 insulin-dependent diabetes mellitus (IDDM). To examine the imbalance in these immunoregulatory cells in Kuwaitis with type-1 diabetes and their first-degree relatives we analysed T-lymphocyte subsets and HLA-DR expression (activation) in 18 IDDM patients with a family history of IDDM and 18 non-diabetic first-degree relatives of the IDDM patients. Both IDDM patients and their first-degree relatives showed a mild lymphopenia. Total T lymphocytes, CD3+ cells, in IDDM patients and their first-degree relatives were reduced compared to control subjects (P < 0.001). Total B lymphocytes, CD19+ cells, was increased in IDDM patients (P = 0.001), but was comparable to controls in IDDM patients' first-degree relatives. No quantitative abnormality was demonstrated in CD4+ cells in IDDM patients; however, these cells were higher in their first-degree relatives (P = 0.0089). Suppressor T lymphocytes, CD8+ cells, in first-degree relatives and controls were not significantly different; however, these cells were significantly reduced in IDDM patients (P = 0.001). The ratio of CD4+/CD8+ cells was higher in IDDM patients and their first-degree relatives compared to controls (P = 0.0007 and 0.0103, respectively). Activated T lymphocytes, HLA-DR+ CD3+ cells, were significantly increased in IDDM patients and their first-degree relatives. HLA-DR3 was the most common antigen found in IDDM patients (77% vs. 20% in controls, P = 0.00021). The second most common antigen was HLA-DR4 (55% vs. 24% in controls, P = 0.0566). However, no relationship was found in the levels of CD3+, CD4+ or CD8+ cells in patients possessing either DR3 or DR4. These results suggest that T-lymphocyte subset imbalance not only characterizes the cellular autoimmunity in the pathogenesis of IDDM but may also be significant in early pre-diabetic stages in those with a family history of IDDM.

Study of HLA class I/IL and T lymphocyte subsets in Kuwaiti vitiligo patients.

HLA polymorphisms of class I and class II MHC were investigated in 40 Kuwaiti vitiligo patients and in 40 controls using microcytotoxicity assay. HLA-B21, Cw6 and DR53 were increased significantly in patients compared to controls (P = 0.00001, 0.00001 and P = 0.0053 respectively) while HLA-A19, DR52, were significantly decreased (P = 0.00236, 0.05, respectively). Total T-cells, T4 and T8 were measured as CD2, CD4 and CD8 respectively by flow cytometry. Vitiligo patients showed significant increase in CD4 compared to controls (P = 0.03). Our findings suggest that HLA-B21 and Cw6 and DR53, are susceptible genes of vitiligo, while A19 and DR52 are protective genes in the Kuwaiti population.

The first HLA anthropological study in the Kuwaiti population.

HLA antigens of the Kuwaiti population are not as well characterized as those of other international ethnic groups. We present results for HLA typing of Kuwaiti individuals using commercial Biotest sera. Six hundred and seventy one Kuwaiti were typed for HLA-A, -B, -C antigens and 399 were typed for HLA-DR, -DQ antigens. Antigen frequency and gene frequency were computed for each phenotype observed. The antigens with the highest frequencies were HLA-A2, A1 and A3; B5, B12 and B7; Cw-4 and Cw-1; DR52, DR5, DR3 and DR7; DQ1 and DQ2. HLA haplotypes with strong linkage disequilibrium and characteristic of Kuwaiti population are A2-B5, A1-B8, B7-DR7 and B8-DR3. A comparison study with other populations is presented.

Reduced levels of CD2+ cells and T-cell subsets in patients with sickle cell anaemia.

Investigation of B lymphocytes and T-lymphocyte subsets in patients with homozygous sickle cell disease (SCD) who were not in crisis and who did not demonstrate infectious complications showed these cell populations to be abnormal. The proportion of total T cells (CD2+) was significantly reduced (P = 0.002) when compared with controls. B cells (CD19+) were significantly elevated in sicklers (P = 0.029). Helper/inducer (CD4+) and suppressor/cytotoxic (CD8+) cells were significantly reduced (P = 0.019 and P = 0.0001, respectively). The average ratio of T cells/B cells in SCD patients was 3.7:1, while controls showed a ratio of 7.2:1. Since patients with SCD are abnormally susceptible to severe infections, we discussed the implications of low levels of CD4+ and CD8+ cells and the consequent cytokine imbalance in SCD patients which may lead to impairment of immunity.

Inhibition of erythroid colony growth in vitro by serum from patients with disseminated bronchial cancer.

The anemia of malignancy is characterized by a reduced output of erythroid cells but with a normal red cell survival. In this study, clonal assays of normal human marrows in the presence of serum from 13 patients with bronchial cancer gave significantly reduced yields of erythroid colonies compared with control cultures with normal serum. More than half the cultures showed no growth of either CFU-E or BFU-E. Four sera producing marked depression of erythroid colony growth had no effect on CFU-GM. The evidence suggests the presence of a circulating inhibitor that may be found in either anemic or nonanemic patients.