Ella Livni

Cell-mediated immunity to human myelin basic protein in schizophrenic patients

Cell-mediated immune response to myelin human basic protein was studied by the macrophage migration inhibition test in patients suffering from schizophrenia. Eighteen out of 32 patients with chronic schizophrenia demonstrated human basic protein-induced inhibition of the migration index, while 4 out of 41 acute schizophrenics showed an inhibition of macrophage migration.

Cell‐mediated immunity to polio and HLA antigens in amyotrophic lateral sclerosis

Cell-mediated immunity to poliovirus was demonstrated in 21 of 33 patients suffering from amyotrophic lateral sclerosis (ALS), whereas no response to poliovirus was found in patients suffering from other neurologic disorders or in healthy controls. Three of the severe bulbar cases produced a migration inhibition factor (MIF) in the presence of poliovirus, although skin tests to common antigens were negative. An increased incidence (46 percent) of HLA-A3 was found in patients with amyotrophic lateral sclerosis. Nine of the 13 patients with HLA-A3 antigen also had a positive index of MIF to poliovirus. These findings suggest a strong linkage between HLA-A3 and poliovirus in the pathogenesis of amyotrophic lateral sclerosis.

In Vitro Release of Interferon-gamma and Macrophage Migration Inhibition Factor in Drug-induced Urticaria and Angioedema

T-cells are involved in the pathogenesis of cutaneous drug reactions. T-cell phenotype and cytokine release pattern in rivo and in vitro might correlate with the type of immune response involved in cutaneous drug reactions. In vitro release of interferon-gamma and macrophage migration inhibition factor (MIF) from peripheral blood lymphocytes, following in vitro challenge with the suspected unmodified drugs, was studied in 12 patients with drug-induced urticaria and/or angioedema and in two group-matched controls. The occurrence of positive interferon-gamma and MIF responses was significantly higher in patients with drug-induced urticaria and/or angioedema than in controls. The sensitivity and specificity of the interferon-gamma test (50% and 92%, respectively) were similar to that of the MIF test (58% and 96%, respectively). Percentage agreement between both tests was 80.9 (kappa = 0.76). In vitro release of interferon-gamma and MIF in drug-induced urticaria and/or angioedema suggests a drug-specific immune response, and may implicate the drug as a possible inducer of the reaction.

Propylthiouracil-induced cholestatic jaundice

The typical propylthiouracil (PTU)-linked hepatotoxicity, is known to manifest itself by hepatocellular injury with greatly increased serum transaminase values and evidence of hepatic necrosis on liver biopsy. Herewith presented is a 33-year old, thyrotoxic woman who developed cholestatic jaundice two weeks after initiation of PTU therapy. The diagnosis was confirmed by liver biopsy. A causal link between PTU treatment and the cholestatic jaundice was suggested by: the time of onset, typical skin rash and a positive migration inhibition factor (MIF) test to PTU. Awareness of this rare complication of PTU treatment may prevent the performance of unnecessary, expensive and possibly harmful diagnostic procedures.

Role of Children's Sex in Mixed Mother-Child Lymphocyte Culture Reactivity

ABSTRACT: One‐way mixed mother‐child lymphocyte cultures (MMCLC) 4 to 20 years after the last delivery were studied with maternal responding and childrens or fathers stimulating cells (MMFLC) in 14 multiple child families with 18 sons and 20 daughters. HLA antigen typing locus A, B, DR was performed for all family members. As reported previously for newborn cells, a significantly increased maternal response could be observed in MMCLC with male as compared to female childrens stimulating cells. Although the number of cases studied was small, it seems that the increased stimulating effect of male childrens cells could also be observed when MMCLC values from children of different sex, and identical A,B,DR haplotypes were compared. In contrast to this, A,B,DR haploidentical children of the same sex seem to have a similar stimulating effect on the maternal response in MMCLC. The results suggest that male childrens Y‐chromosome‐correlated minor histocompatibility antigens may additionally stimulate the maternal immune response in MMCLC.

Treatment of recurrent spontaneous abortions by immunization with paternal lymphocytes induces immunosuppression by placental isoferritin.

PROBLEM: The immunological mechanism leading to an effective vaccination of unexplained habitual aborters with paternal lymphocytes is not yet elucidated. Since previous studies revealed that immunosuppression by placental isoferritin (PLF) may play an important role in the down regulation of the immune system during pregnancy, it was of interest to investigate whether alloimmunization activates immunosuppression by PLF.

Soluble histocompatibility antigen class I in breast cancer patients in relation to tumor burden

Serum beta‐2 microglobulin (B‐2M) levels were studied in 365 breast cancer patients and 210 age‐matched controls. The patients were divided into three groups: Group A, new patients at diagnosis; Group B, patients at follow‐up; and Group C, metastatic patients. The mean B‐2M of all breast cancer patients plus or minus one standard deviation (3.5 ± 1.2; range, 1.1 to 5.9) was significantly higher than normal controls (1.29 ± 0.49; range, 0.3 to 2.3; P < 0.005). When the three patient groups were compared with each other, the mean B‐2M level of Group A (3.0 ± 1.5; range, 0.9 to 6.9) was similar to that of Group C (4.22 ± 1.1; range, 2.0 to 6.4). The mean B‐2M of both Groups A and C was significantly higher than that of Group B (2.38 ± 1.02, range, 0.4 to 5.4; P < 0.001). In Group A the mean B‐2M decreased significantly after a 12‐month period and reached the mean level of Group B but not that of normal controls. When patients in Group B were analyzed by their stage of disease at diagnosis, there was no significant difference between Stages I and II. There was a significant difference in the mean B‐2M levels between Stages I and III. In relapsing patients, mean B‐2M levels increased. These findings suggest that serum B‐2M levels may reflect tumor burden, and even in patients at follow‐up, occult tumor cells may activate the immune system.

Case report. Immunological studies in a case of hepatitis following methyldopa administration.

Jaundice with evidence of hepatocellular damage of moderate severity was observed in a patient who received methyldopa. The diffuse mononuclear infiltration of the liver tissue was found to consist of 90% E-rosette-forming cells. Peripheral lymphocytes gave a markedly positive macrophage migration inhibition (MIF) test against methyldopa. The number of T lymphocytes in the peripheral blood was at the lower limit of normal but they proved to be functionally inactive, as demonstrated by the results of a local xenogeneic graft-vs-host reaction test. The liver disease was associated with hyperglobulinemia, a decrease of the third and fourth components of complement and the presence of incomplete erythrocytic antibodies, leukoagglutinins, antinuclear factor, and smooth muscle antibody. Follow-up after discontinuation of the drug revealed a gradual return to normal of liver function and MIF tests, normalization of cellular immunity, and disappearance of the humoral antibodies. It is assumed that sensitization by methyldopa triggered the autoaggressive phenomena and their ultimate manifestation in the liver.

The role of macrophage migration inhibition factor in toxic epidermal necrolysis.

Patient A A 60‐year‐old man developed toxic epidermal necrolysis (TEN) following several weeks of treatment with two kinds of drug: co‐trimoxazole and acetazolamide. On the basis of time relationship data, both drugs could be considered as the inducers of the cutaneous reaction.1 Guide fables indicated that co‐trimoxazole is one of the most common inducers of TEN, whereas acetazolamide has been reported as a possible uncommon inducer of TEN.1–3 Drug intake was stopped, and treatment with prednisone (120 mg/day) was instituted, followed by a gradual tapering of the dosage. A month later, complete remission of the skin lesions was observed. A macrophage migration inhibition factor (MIF) test was performed towards the drugs taken, in an attempt to identify the offending drug. The macrophage migration inhibition factor (MIF) test was positive towards co‐trimoxazole and negative for acetazolamide. Positive MIF responses towards co‐trimoxazole were not recorded in ten control patients (control I) treated with the drug with no manifestations of drug eruption.

Case Report Hepatitis Following Cimetidine Administration

There have been only two reports of cimetidine-induced hepatitis. Such a low incidence suggests a hypersensitivity type of reaction. The case of an adult who developed both hepatic dysfunction and an impaired macrophage migration after exposure to cimetidine is discussed.