A-beta-lipoproteinemia: clinical and laboratory features, therapeutic manipulations, and follow-up study of three members of a Greek family.

We describe the clinicoepidemiologic features, natural history, and therapeutic manipulations in three Greek patients with A-beta-lipoproteinemia (two brothers aged 15 and 29 years, respectively, and one sister aged 30 years). Diarrhea started in infancy in the two brothers and from the age of 13 in the sister. During the second decade of life, central nervous system symptoms became prominent, with fatigue and disturbance in gait and balance. Night blindness developed at a later phase of the disease in the brothers, whereas cavus developed in both legs in the sister. Apolipoprotein B was absent in all patients, and each had more than 50% of acanthocytes present on peripheral smear. The diagnosis of A-beta-lipoproteinemia was established on the basis of small bowel histology and serum lipid estimations. Family studies revealed normal lipid profiles in all healthy members. The human leukocyte antigen (HLA) pattern in the two most severely affected patients was identical. The only detectable difference between the severely ill patients and other members of the family, however, was homozygosity for the HLA B18 antigen, whereas the third patient had no alleles for the HLA B18 antigen. Treatment consisted of a low-fat diet and high doses of vitamins A and E. A modified diet substituting medium-chain triglycerides for dietary fat was also given, with significant improvement in the nutritional status of patients but not in symptoms related to advanced disease, such as retinal and cardiac manifestations. We conclude that the course of the disease in untreated patients is characterized by continuous symptoms. Some of the symptoms, however, especially those related to malabsorption, as well as some anthropometric parameters can be improved by the application of a modified diet including medium-chain triglycerides. We suggest the routine measurement of plasma lipids and apoproteins not only in children with failure to thrive, with unexplained malabsorption, or with neurologic symptoms, but also in adults with chronic diarrhea accompanied by neurologic symptoms or clinical and laboratory signs of malabsorption.

Serum concentrations of soluble intercellular adhesion molecule-1 and progress towards disease in patients infected with HIV.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell to cell adhesive interactions of the immune system. Concentrations of soluble ICAM-1 (s-ICAM-1) shed into the circulation were measured by a quantitative ELISA in HIV-infected persons without AIDS, patients with AIDS with or without evidence of acute opportunistic infection at the time of sampling, and HIV-seronegative patients with toxoplasmosis, community-acquired pneumonia, leishmaniasis and rickettsial infections. Patients were classified on the basis of clinical condition and CD4+ T-cell counts according to the 1993 revised HIV classification of the USA Centers for Disease Control. Concentrations of s-ICAM-1 in the serum of HIV-infected persons without AIDS-indicator conditions (categories A1, A2, B1 and B2) as well as in the serum of patients with AIDS (categories A3, B3, C1, C2 and C3) were significantly higher than normal (mean +/- S.E.M. 469 +/- 23, n = 60 and 780 +/- 73, n = 56, respectively, versus 329 +/- 15 ng/ml, P < 0.0001 and < 0.0001 respectively) and differed also significantly from each other (P < 0.0001). Raised concentrations of s-ICAM-1 in the serum of afebrile patients with AIDS but without acute opportunistic infection at the time of sampling (mean +/- S.E.M. 672 +/- 76, n = 29) did not differ from those of the remaining patients with AIDS or from those of HIV-seronegative patients with the infections studied. A steady and significant increase of serum concentrations of s-ICAM-1 with progress of disease according to clinical category (categories A-->B-->C, p = 0.0007) as well as with the loss of circulating CD4+ T-cells (categories 1-->2-->3, p = 0.009) was observed. Individual serum concentrations of s-ICAM-1 showed negative correlations with individual total lymphocyte (P = 0.004), CD4+ T-cell (P = 0.05), CD8+ T-cell counts (P = 0.03) as well as positive correlation with serum concentrations of soluble interleukin-2 receptors (P < 0.0001), an indirect marker of progress of HIV-related disease. Serum concentrations of s-ICAM-1 did not differ between patients with AIDS who were receiving or not receiving zidovudine at the time of sampling. A longitudinal survey is needed in order to determine whether measuring serum concentrations of s-ICAM-1, although not specific, has any predictive or prognostic value in these patients as well as whether this bioactive molecule has any pathogenetic role in the progress of disease in HIV infection.

Immune status of Greek patients with beta-thalassemia major negative for anti-HIV.

Patients with thalassemia who receive multiple blood transfusions are at risk for the acquired immunodeficiency syndrome. Peripheral blood lymphocyte subpopulations were studied in 22 multitransfused thalassemic patients; 10 patients were without splenectomy and 12 were studied after splenectomy. Both groups were negative for anti-HIV. Four additional patients who were found positive for anti-HIV and ten healthy controls were also included in this study. Patients without splenectomy compared to controls and to patients after splenectomy showed a significant decrease of both percentage (p less than 0.001) and absolute numbers (p less than 0.001) of Leu-7+ cells without significant abnormalities of T4/T8 ratio (1.56 +/- 0.4). Patients after splenectomy compared to controls and to patients without splenectomy showed a significant increase of the absolute numbers of lymphocytes and lymphocytes subsets T11+, T3+, T4+, T8+ and SmIg+ cells. In the seropositive patients for HIV only a significant increase of the absolute number of T8+ cells was observed while the T4/T8 ratio was 1.24 +/- 0.73. The decrease in the percentage of Leu-7+ cells in patients without splenectomy correlated inversely to the total amount of blood transfused. In conclusion patients with thalassemia had normal T4/T8 ratio and did not show the abnormal immunologic profile that has been reported in haemophiliacs.

Lymphocyte markers and clinical expression of lymphoproliferative disorders with moderate lymphocytosis.

Lymphoproliferative syndrome with well differentiated lymphocytes and moderate lymphocytosis in the peripheral blood includes a heterogeneous group of disorders, that present often difficulties in classification. We have studied the lymphocyte markers (ER, EMR, sIg and T3, T4, T8 antigens) in 36 cases who had lymphocytic infiltration in the bone marrow and peripheral lymphocyte counts less than 15 X 10(9) l-1. Four cases (11.1%) had the characteristics of T8 lymphocytosis and 31 had a B cell monoclonal proliferation in the peripheral blood. Of these, four were sIg-, EMR+, 19 were sIg+, EMR+ and 8 were sIg+, EMR-. Most patients (17/32) had the clinical picture of stage 0 and I B-CLL. Six cases presented as pure splenomegalic form of CLL, three had the features of immunocytic lymphoma and five had the features of lymphocytic lymphoma. It is concluded that the majority of lymphoproliferative disorders presenting with moderate lymphocytosis represent early forms of B-CLL. Occasionally cases of lymphocytic or immunocytic lymphoma may present problems of differential diagnosis since there may be a dissociation of phenotypic characteristics of lymphocytes between tissues and peripheral blood.

Abnormalities of lymphocyte subsets and anti-LAV/HTLV-III status in Greek hemophiliacs.

Peripheral blood lymphocyte subsets and the incidence of LAV/HTLV-III antibodies were studied in 63 patients with hemophilia A who had been transfused with a low dose regimen of commercial (U.S.A.) factor VIII concentrates. Five patients with hemophilia B were also included in this study. In hemophilia A patients a significant reduction in the percentage and absolute numbers of T4+ cells and of the T4/T8 ratio and a significant increase in the percentage of T8+ and Leu-7+ cells were observed. These abnormalities were independent of the presence of anti-LAV/HTLV-III. In hemophilia B patients a significant increase of T8+ cells and a decrease of T4/T8 ratio was noted while the percentage of Leu-7+ cells was normal. A significant negative correlation of F VIII units transfused and T4/T8 ratio was seen only in LAV/HTLV (-) patients, suggesting that F VIII per se could cause immunodysregulation. Seropositive patients were found to have consumed a larger amount of F VIII units than seronegative patients during the period 1980-1984 (p less than 0.005).

Blood lymphocyte subpopulations studied with monoclonal antibodies in aleukaemic stages of mycosis fungoides.

Peripheral blood lymphocytes from 21 patients with aleukaemic stages of mycosis fungoides were studied with monoclonal T cell antibodies. Patients with erythematous eruptions or infiltrated plaques (group I) had a higher percentage of OKT4+ cells than patients with a tumorous stage (group II) or normal subjects (p = 0.05). OKT8+ cells were decreased in group I patients whereas in group II they were usually normal or increased (p less than 0.02). These data indicate that with advancing stage of the disease a different pattern of imbalance of T-cell subsets is being established.

Prevalence of autoimmune diseases and autoantibodies in Ethiopia.

Analysis of 7,966 hospital admissions and other available data suggest that disease associated with autoimmunity are rare in Ethiopia. Sera from 107 patients with dyspepsia and 80 healthy Ethiopians were studied for autoantibodies. Using the immunofluorescence technique and anti-Fab-FITC conjugate, a search for organ-specific autoantibodies against thyroid (microsomal and thyroglobulin) cells as well as for non-organ-specific autoantibodies against nuclear material, smooth muscle, mitochondria, cardiolipin, glomerular basement membrane and connective tissue (reticulin antibodies) revealed that they were uncommon. Thus, both clinical and serological studies confirm that previously held views concerning the rarity of autoimmune diseases in many parts of Africa are also true in Ethiopia. It is suggested that the few Ethiopians who develop autoimmune diseases may have an overwhelming hereditary predisposition which is unable to overcome inhibitory factors in the environment.