Effects of Helminth Eradication on the Immune System.

INTRODUCTION: Helminth infection has a profound effect on the immune system. However, the precise nature of the immune changes that are elicited by helminth infection have not been sufficiently characterized. Furthermore, the reversibility of these changes after treatment has not been documented sufficiently. We studied the immune profiles of Ethiopian immigrants to Israel at baseline, that is on arrival and at one-year follow-up and compared individuals who received antihelminth treatment during the study period with those who missed the treatment. METHODS: A longitudinal follow up study involving different groups of subjects was conducted. Baseline data was recorded from the newly arrived Ethiopian immigrants for a series of peripheral blood tests, including: IgE and Eosinophil levels, T-cell populations, T-cell receptor phenotypes, and cytokine measurement. These tests were all repeated after a 1-year interval. Results were compared between the newly arrived Ethiopian immigrants (NEW-Eth-Il), long term Ethiopian immigrants (LT-Eth-Il), and non Ethiopian Israeli controls (NON-Imm-Il). RESULTS: Of the 184 individuals, 111 were NEW-Eth-Il, who had a high prevalence of helminth infection, the immunological changes were elevated IgE levels and eosinophil counts, decreased CD4/CD8 ratio, increased proportion of HLA-DR+CD3+, HLA-DR+CD4+ and HLA-DR+CD8+ cells, decreased proportion of CD45RA+CD4+ (naive) and CD28+CD8+ cells, increased proportion of CD45RO+CD4+ (memory) cells, and increased secretion of IL-4 and IL-5 (Th2 type cytokines). In the 42 LT-Eth-Il participants, who all had negative tests for helminth infection, we did not observe these immune changes and their immune profile did not differ markedly from that of the NON-Imm-Il controls. The follow-up immune profiles of 33 NEW-Eth-Il who received succesful antihelminth treatment, showed a significant normalization in the above-mentioned variables that was not observed in the 19 NEW-Eth-Il who missed and did not receive the antihelminth treatment. CONCLUSIONS: These findings demonstrate that helminth infection is associated with profound immune changes that are normalized within a short time after helminth eradication. They also strengthen the hypothesis that effective antihelminth interventions, in areas endemic for intestinal helminths, may have an impact on AIDS and tuberculosis epidemics.

Serum immunoglobulin E levels in Israeli-Ethiopian children: environment and genetics.

BACKGROUND: Since 1984, several waves of Ethiopian immigrants have settled in Israel. On arrival they were found to be highly infected with intestinal parasites and to have increased serum immunoglobulin E and eosinophilia. OBJECTIVES: To study serum IgE levels in Ethiopian children growing up in the environment of Israel. METHODS: We assessed four groups of children of Ethiopian origin: a) adolescents examined on their arrival to Israel (group 1, n=11); b) adolescents born in Ethiopia and living in Israel for more than 7 years (group 2, n=10); c) children of Ethiopian origin born in Israel, without a history of allergy or asthma (group 3, n=15); and d) asthmatic children of Ethiopian origin born in Israel (group 4, n=8). A thorough clinical interview and examination as well as laboratory work up (including serum IgE levels, stool parasites and absolute eosinophil count) were performed. RESULTS: Group 1 (11 newly arrived Ethiopian adolescents) had a mean eosinophil count of 688 cells/ml (0-1739) and a mean serum IgE of 1043 IU/ml (253-2932), P< 0.0009 as compared to group 2. Helminthic parasites were observed in 8/11 individuals; after 1 year of follow-up and anti-parasitic treatment, serum IgE levels did not change significantly. Group 2 (10 Ethiopian born adolescents living in Israel for on average 10 years, 7-15 years) had a normal leukocyte count, MEC 192 cells/ml (range 54-289), serum IgE 142 IU/ml (range 14-399 IU/ml) and no parasites in stool. Group 3 (15 Ethiopian children born in Israel) had a normal leukocyte count, MEC 128 cells/ml (0-324), serum IgE 55 IU/ml (7-189 IU/ml), similar to age-matched Israeli controls. In group 4 (8 Israeli born children of Ethiopian descent diagnosed with asthma), serum IgE showed significant elevation compared to Israeli age-matched asthmatic children (P< 0.005). CONCLUSIONS: High levels of IgE found in Ethiopian children on arrival to Israel declined to Israeli control levels after several years of living in the new environment. Ethiopian children born in Israel had normal levels of IgE, suggesting that environment is the main factor affecting IgE levels in this population. Israeli born Ethiopian children with asthma had significantly increased serum IgE levels compared to asthmatics of Israeli origin. These findings suggest that both environmental and genetic factors determine the level of serum IgE in these children.

Generation of Th1 immune responses to inactivated, gp120-depleted HIV-1 in mice with a dominant Th2 biased immune profile via immunostimulatory [correction of imunostimulatory] oligonucleotides--relevance to AIDS vaccines in developing countries.

Vaccination against HIV-1 of hosts with a dominant Th2 immune profile may fail to induce essential protective Th1 immune responses. By using Schistosoma-infected mice, with a pre-existent Th2 immune background, we demonstrate that oligodeoxynucleotides (ODN) containing unmethylated cytosine-phosphate-guanosine (CpG) immunostimulatory sequences co-administered with inactivated, gp120-depleted HIV-1 viral particles (HIV-1 immunogen) lead to potent Th1 anti-HIV-1 immune responses overcoming the Th2 bias. In contrast, Schistosoma-infected mice immunized with HIV-1 immunogen in incomplete Freund's adjuvant only, induced Th2 anti-HIV-1 immune responses. These findings strongly support the advisability of using CpG ODN as a Th1 inducing adjuvant when immunizing human populations with a strong pre-existent Th2 immune profile.