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The Regulation of Inherently Autoreactive VH4-34-Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa.

ABSTRACT: Plasmodium falciparum malaria is a deadly infectious disease in which Abs play a critical role in naturally acquired immunity. However, the specificity and nature of Abs elicited in response to malaria are only partially understood. Autoreactivity and polyreactivity are common features of Ab responses in several infections and were suggested to contribute to effective pathogen-specific Ab responses. In this article, we report on the regulation of B cells expressing the inherently autoreactive VH4-34 H chain (identified by the 9G4 mAb) and 9G4+ plasma IgG in adults and children living in a P. falciparum malaria-endemic area in West Africa. The frequency of 9G4+ peripheral blood CD19+ B cells was similar in United States adults and African adults and children; however, more 9G4+ B cells appeared in classical and atypical memory B cell compartments in African children and adults compared with United States adults. The levels of 9G4+ IgG increased following acute febrile malaria but did not increase with age as humoral immunity is acquired or correlate with protection from acute disease. This was the case, even though a portion of 9G4+ B cells acquired phenotypes of atypical and classical memory B cells and 9G4+ IgG contained equivalent numbers of somatic hypermutations compared with all other VHs, a characteristic of secondary Ab repertoire diversification in response to Ag stimulation. Determining the origin and function of 9G4+ B cells and 9G4+ IgG in malaria may contribute to a better understanding of the varied roles of autoreactivity in infectious diseases.

SUBMITTER: Hart GT

PROVIDER: S-EPMC5113821 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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The Regulation of Inherently Autoreactive VH4-34-Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa.

Hart Geoffrey T GT Akkaya Munir M Chida Asiya S AS Wei Chungwen C Jenks Scott A SA Tipton Christopher C He Chenfeng C Wendel Ben S BS Skinner Jeff J Arora Gunjan G Kayentao Kassoum K Ongoiba Aissata A Doumbo Ogobara O Traore Boubacar B Narum David L DL Jiang Ning N Crompton Peter D PD Sanz Ignacio I Pierce Susan K SK

Journal of immunology (Baltimore, Md. : 1950) 20161019 10

Plasmodium falciparum malaria is a deadly infectious disease in which Abs play a critical role in naturally acquired immunity. However, the specificity and nature of Abs elicited in response to malaria are only partially understood. Autoreactivity and polyreactivity are common features of Ab responses in several infections and were suggested to contribute to effective pathogen-specific Ab responses. In this article, we report on the regulation of B cells expressing the inherently autoreactive VH ...[more]

PMID: 27798155

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Project description:ObjectivesTo study the manifestations of Plasmodium infection, and its relations with the malaria disease, especially when comparing dry and rainy seasons in a hyperendemic area of West Africa.MethodsThe study was carried out in an area where malaria transmission is high, showing important seasonal variations. One thousand children, representing the total child population (1-12 year old), were observed transversally at the end of three consecutive seasons (dry/rainy/dry). The usual indicators, such as parasite density, splenomegaly, anaemia, or febrile disease were recorded and analysed.ResultsThe prevalence of Plasmodium falciparum was high in all age groups and seasons, constantly around 60%. The high transmission season (rainy) showed higher rates of anaemia and spleen enlargement and, in the youngest children only, higher parasite densities. There were also differences between the two dry seasons: in the first one, there was a higher rate of fever than in the second one (p < 0.001). Low parasite density (<2,000 p/?l) was never associated with fever during any season, raising some concern with regard to the usefulness of parasite detection. The possible origins of fever are discussed, together with the potential usefulness of analyzing these indices on a population sample, at a time when fever incidence rises and malaria is one potential cause among others. The distinction to be made between the Plasmodium infection and the malaria disease is highlighted.ConclusionsThese data confirm previous hypotheses of a strong difference in malaria infection and disease between dry and rainy seasons. The most relevant seasonal indicator was not mainly parasite rate and density but anaemia, spleen enlargement, prevalence and possible origin of fever.RecommendationsIn any situation (i.e. fever or not) and especially during the dry season, one must consider that detection of parasites in the blood is only evidence of a Plasmodium infection and not necessarily of a malaria disease. In such a situation, it seems suitable to obtain, through national malaria teams, a well-defined situation of transmission and prevalence of Plasmodium infection following zones and seasons, in order to adapt control strategies. For researchers, a systematic management of data separately for dry and rainy season appears mandatory.

Project description:BACKGROUND:Non-Plasmodium falciparum malaria infections are found in many parts of sub-Saharan Africa but little is known about their importance in pregnancy. METHODS:Blood samples were collected at first antenatal clinic attendance from 2526 women enrolled in a trial of intermittent screening and treatment of malaria in pregnancy (ISTp) versus intermittent preventive treatment (IPTp) conducted in Burkina Faso, The Gambia, Ghana and Mali. DNA was extracted from blood spots and tested for P. falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale using a nested PCR test. Risk factors for a non-falciparum malaria infection were investigated and the influence of these infections on the outcome of pregnancy was determined. RESULTS:P. falciparum infection was detected frequently (overall prevalence by PCR: 38.8 %, [95 % CI 37.0, 40.8]), with a prevalence ranging from 10.8 % in The Gambia to 56.1 % in Ghana. Non-falciparum malaria infections were found only rarely (overall prevalence 1.39 % [95 % CI 1.00, 1.92]), ranging from 0.17 % in the Gambia to 3.81 % in Mali. Ten non-falciparum mono-infections and 25 mixed falciparum and non-falciparum infections were found. P. malariae was the most frequent non-falciparum infection identified; P. vivax was detected only in Mali. Only four of the non-falciparum mono-infections were detected by microscopy or rapid diagnostic test. Recruitment during the late rainy season and low socio-economic status were associated with an increased risk of non-falciparum malaria as well as falciparum malaria. The outcome of pregnancy did not differ between women with a non-falciparum malaria infection and those who were not infected with malaria at first ANC attendance. CONCLUSIONS:Non-falciparum infections were infrequent in the populations studied, rarely detected when present as a mono-infection and unlikely to have had an important impact on the outcome of pregnancy in the communities studied due to the small number of women infected with non-falciparum parasites.

Dataset Information

The Regulation of Inherently Autoreactive VH4-34-Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa.

Publications

The Regulation of Inherently Autoreactive VH4-34-Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa.

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