Immunologic properties of methionine-enkephalin, and therapeutic implications in AIDS, ARC, and cancer.
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Biomedical subjects
Publications and source records attributed to H Taelman.
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After the demonstration of cytophilic IgE immunoglobulins (Ig) on human blood and lung eosinophils, their role in cell activation was studied by eosinophil peroxidase (EPO) assay. Hypodense human eosinophils from filariasis-infected patients were activated by anti-human Ig or various antigens. A selective release of EPO occurred after incubation with anti-human IgE, but not with anti-human IgG. The activation by antigens showed a strict antibody specificity of cytophilic IgE antibodies. The direct involvement of IgE antibodies in activation by the specific antigen was evidenced by inhibition experiments with aggregated human IgE myeloma protein. Circulating IgE antibodies exhibiting the same specificity and able to induce EPO release were detected in the sera from filariasis patients by a passive sensitization assay. Only the hypodense eosinophils were able to release EPO after IgE-dependent activation both in the direct assay and in the passive sensitization test, confirming the functional heterogeneity of human eosinophils. These results suggest that the interaction between IgE antibodies and human eosinophils can play a role both in protective immunity and pathology by releasing active pharmacologic mediators.
From December 1982 to June 1985, we diagnosed LAV/HTLV-III infection in 16 children of African origin living in Belgium or referred to one of the hospitals participating in this study. Diagnosis was proven in seven of them by isolation of virus of the LAV/HTLV-III group. In the nine others, LAV/HTLV-III infection was highly probable because of the presence of antibodies against the virus (seven subjects) or clinical and immunological evidence of immune deficiency associated with a parental history of LAV/HTLV-III infection (two subjects). Five of these children had a severe illness starting in the first months of life (range 20 days--4 months) and died within 4 months (range 19 days--10 months). Eight children presented later in life (mean age 35 months, range 2-66 months) with a milder and more chronic disease characterized by the presence of generalized lymphadenopathy (6/8), hepatomegaly (5/8), splenomegaly (5/8), interstitial pulmonary infiltration (4/8), parotid swelling (3/8), CSF lymphocytosis (3/5), diarrhoea without pathogen isolated (1/8) and fever (1/8). At least one of the parents of each child was of African origin. At the time of birth of their child two mothers and one father had an AIDS-related complex. After a mean period of 34 months (range 3-87 months) five fathers and six mothers had a symptomatic LAV/HTLV-III infection (AIDS or AIDS-related complex).
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Twenty-seven histologically confirmed Kaposi sarcoma (KS) patients resident in the Kivu Lake area of eastern Zaire were examined for immune competence. Only KS cases of the endemic African type have been observed in this high-incidence area. The median duration of the symptoms was 6 years and ranged from 1 to 38 years. Forty-one controls matched for age, sex and tribe and unrelated to the KS patients were selected from the community. Thirteen additional controls were first-degree relatives of the KS patients. No evidence of immune suppression among KS patients was found and there were no significant differences in the immune status between KS patients and controls. Total lymphocytes, B and T cells, and OKT4+ and OKT8+ cells varied within the normal range. Grouping of the KS patients in categories according to duration and disease extent did not reveal significant differences in their immune status. The number of KS patients reacting positively in a skin test to 5 recall antigens and I mitogen was similar to that of controls, except in the case of candidin, to which a higher number of KS patients were negative. The serum levels of immunoglobulins, complement factors and circulating immune complexes were comparable in KS patients and controls. Indicators of inflammatory processes [white blood cells (WBC), complement-reactive protein (CRP)] were positive in 27% of the KS patients. The prevalence and mean titer of antibody against cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B virus (HBV) and syphilis were similar in KS patients and in controls.
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An adult Belgian patient with visceral leishmaniasis acquired while on holiday in Spain is described. This patient's cellular immunity was assessed by skin testing using six different antigens and was normal just before leaving for Spain. During the leishmaniasis, skin tests with the same antigens showed complete anergy. Lymphocyte transformation tests to antigens and mitogens were severely impaired but normal T cell subsets determined by OKT monoclonal antibodies were found. Immune complexes, containing antibodies to Leishmania antigen were isolated during the patient's illness. It is most likely that visceral leishmaniasis caused the functional cellular immune impairment of the patient.
A patient with intravitreous cysticercosis was treated with the new anthelminthic drug, praziquantel. A transient toxic effect on the cysticerus was observed, but the drug was unable to kill the parasite.
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38 patients with the acquired immunodeficiency syndrome (AIDS) were identified in Kinshasa, Zaire, during a 3 week period in 1983. The male to female ratio was 1.1:1. The annual case rate for Kinshasa was estimated to be at least 17 per 100 000. Opportunistic infections were diagnosed in 32 (84%) patients, disseminated Kaposi's sarcoma (KS) with opportunistic infection in 5 (13%), and disseminated KS alone in 1 patient. Immunological characteristics of these patients were as reported for cases in the USA and Europe, but immunological abnormalities were also found in 6 controls with infectious diseases but no symptoms of AIDS. Female AIDS cases were younger than male patients with AIDS (mean ages 28.4 vs 41.1 years, respectively), and were more often single (14/18 vs 2/20). Homosexuality, intravenous drug abuse, and blood transfusion did not appear to be risk factors in these patients. The findings of this study strongly argue that the situation in central Africa represents a new epidemiological setting for this worldwide disease--that of significant transmission in a large heterosexual population. Two instances of clusters of AIDS (not included in the above series) involving males and females with frequent heterosexual contact further implicate heterosexual transmission.
Between May 1979 and April 1983, 18 previously healthy African patients were hospitalized in Belgium with opportunistic infections (cryptococcosis, Pneumocystis carinii pneumonia, central-nervous-system toxoplasmosis, progressive cutaneous herpes simplex virus infection, disseminated cytomegalovirus infection, candidiasis, or cryptosporidiosis) or Kaposi's sarcoma, or with both. Ten of them died. During the same period five other patients were hospitalized with an illness consistent with a prodrome of the acquired immunodeficiency syndrome (chronic lymphadenopathy, fever, weight loss, and diarrhea). All patients tested had a marked decrease in helper T cells; an inversion of the normal ratio of helper to suppressor T cells, and a decreased or absent blastogenic response of lymphocytes to mitogens. Twenty patients had anergy. There was no evidence of an underlying immunosuppressive disease and no history of blood-product transfusion, homosexuality, or intravenous-drug abuse. This syndrome in patients originating in Central Africa is similar to the acquired immunodeficiency syndrome reported in American patients.
During the years from 1979 until 1983, 40 cases of CDC-defined AIDS were seen in Belgium. Only two patients were Belgian male homosexuals. The other patients were Central Africans who lived in Belgium or who had travelled to Belgium for medical care. There was no evidence of an underlying immunosuppressive disease, and no history of homosexuality or intravenous drug abuse. The male:female ratio was 1.5. All patients had opportunistic infections. Five of them also had Kaposi's sarcoma. All patients tested had immunologic features of severe T-cell depression. The overall mortality was 42.5 percent. It is likely that AIDS is endemic now in Central Africa, and that the cases seen in Belgium represent only the tip of the iceberg.
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