RESUMO
Lymphatic filariasis (LF) is a parasitic disease caused by the worms Wuchereria bancrofti, Brugia malayi, or Brugia timori. It is a tropical and subtropical illness that affects approximately 67 million people worldwide and that still requires better diagnostic tools to prevent its spread and enhance the effectiveness of control procedures. Traditional parasitological tests and diagnostic methods based on whole protein extracts from different worms are known for problems related to sample time collection, sensitivity, and specificity. More recently, new diagnostic tools based on immunological methods using recombinant antigens have been developed. The current review describes the several recombinant antigens used as tools for lymphatic filariasis diagnosis in antigen and antibody capture assays, highlighting their advantages and limitations as well as the main commercial tests developed based on them. The literature chronology is from 1991 to 2021. First, it describes the historical background related to the identification of relevant antigens and the generation of the recombinant polypeptides used for the LF diagnosis, also detailing features specific to each antigen. The subsequent section then discusses the use of those proteins to develop antigen and antibody capture tests to detect LF. So far, studies focusing on antibody capture assays are based on 13 different antigens with at least six commercially available tests, with five proteins further used for the development of antigen capture tests. Five antigens explored in this paper belong to the SXP/RAL-2 family (BmSXP, Bm14, WbSXP-1, Wb14, WbL), and the others are BmShp-1, Bm33, BmR1, BmVAH, WbVAH, BmALT-1, BmALT-2, and Wb123. It is expected that advances in research with these antigens will allow further development of tests combining both sensitivity and specificity with low costs, assisting the Global Program to Eliminate Lymphatic Filariasis (GPELF).
Assuntos
Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/genética , Antígenos de Helmintos/imunologia , Filariose Linfática/diagnóstico , Filariose Linfática/parasitologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/classificação , Brugia/química , Brugia/imunologia , Filariose Linfática/classificação , Proteínas de Helminto/genética , Proteínas de Helminto/imunologia , Humanos , Imunoglobulina G/imunologia , Sensibilidade e Especificidade , Wuchereria bancrofti/química , Wuchereria bancrofti/imunologiaRESUMO
Previous reports have demonstrated age-related shifts in antifilarial humoral immune responses in 6- to 10-year-old Haitian children; the responses consisted of elevated parasite-specific IgG2 and IgG3 in amicrofilaremic children and elevated IgG4 in microfilaremic children. In this study, the cell-mediated immune responses to soluble adult and microfilarial extracts of Brugia pahangi, determined by use of a microblastogenesis assay, were examined. Capillary blood samples were collected by finger prick from 176 Haitian children in an area with endemic Wuchereria bancrofti. Antigen-specific cellular responsiveness varied as a function of infection status but not age or sex; amicrofilaremic children had significantly greater responses to adult antigens than did microfilaremic children. Significant responses were detected in children less than 2 years of age; thus, correlations observed between filarial antigen-specific responses and infection status are established early in life.
Assuntos
Filariose/imunologia , Ativação Linfocitária , Adolescente , Fatores Etários , Animais , Brugia/imunologia , Criança , Pré-Escolar , Feminino , Filariose/sangue , Haiti , Humanos , Imunidade Celular , Lactente , MasculinoRESUMO
Previous studies of antifilarial antibodies in a pediatric population residing in an area with endemic Wuchereria bancrofti filariasis have demonstrated age related shifts in antifilarial immunity. To further characterize humoral responses in Haitian children, serum samples from 129 patients (3 months-15 years of age) were analyzed by ELISA for isotype-specific antifilarial antibody responses. Age-stratified analysis of geometric mean antibody titers showed significant increases in antibody titers of all isotypes with age in the amicrofilaremic population. Antifilarial IgG1, 2, and 3 levels were higher in amicrofilaremic children than in microfilaremic children, significantly so for IgG2 and IgG3. In contrast, IgG4 antibody levels were higher in microfilaremic subjects than in amicrofilaremic subjects. A multivariate, unconditional, logistic regression model was developed from these data to predict infection status. The model correctly classified 91.6% of the amicrofilaremic subjects, but only 55.6% of the microfilaremic subjects.
Assuntos
Anticorpos Anti-Helmínticos/sangue , Brugia/imunologia , Filariose/imunologia , Imunoglobulina G/análise , Adolescente , Animais , Criança , Pré-Escolar , Filariose Linfática/diagnóstico , Filariose Linfática/epidemiologia , Filariose Linfática/imunologia , Filariose Linfática/parasitologia , Ensaio de Imunoadsorção Enzimática , Feminino , Filariose/diagnóstico , Filariose/epidemiologia , Filariose/parasitologia , Haiti , Humanos , Lactente , Masculino , Microfilárias/imunologia , Microfilárias/isolamento & purificação , Modelos Estatísticos , Análise MultivariadaRESUMO
The immunological consequences of exposure to filarial infection were examined by cross-sectional serological studies. Serum samples from 121 pediatric patients (18 months-15 years of age) were analyzed in parallel with a panel of sera from adults residing in the same area of Haiti. Parasite antigen specific IgG and IgE levels were determined by ELISA. IgG levels in children were significantly elevated in humoral immunoreactivity to Brugia pahangi extracts compared to adults. In addition, anti-filarial IgG levels in amicrofilaremic children were significantly greater than in microfilaremic children. In contrast, IgG levels in adults were equivalent independent of microfilaremic status. Anti-filarial IgE levels in sera from both children and adults were low in comparison to that of a subject with tropical pulmonary eosinophilia and were unrelated to clinical status. No correlations were found between humoral responses and age, sex, or degree of parasitemia. Sera from amicrofilaremic children and, to a lesser extent, adults recognize more antigens, particularly those of high molecular weight (greater than 55 kDa), than sera from microfilaremic patients.
Assuntos
Anticorpos Anti-Helmínticos/análise , Brugia/imunologia , Filariose Linfática/imunologia , Filariose/imunologia , Imunoglobulina E/análise , Imunoglobulina G/análise , Adolescente , Adulto , Fatores Etários , Animais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Haiti , Humanos , Lactente , Masculino , Microfilárias/imunologia , Pessoa de Meia-IdadeRESUMO
Patent infections with the lymphatic filariae, Wuchereria bancrofti and Brugia malayi, are associated with suppressed in vitro cellular responsiveness to filarial antigens. In studies of bancroftian filariasis in Haiti, a significant number of microfilaremic individuals can be characterized as "responders" to filarial antigens. Cells from 37/74 untreated microfilaremic subjects responded to B. pahangi antigen (stimulation ratio greater than 2) as detected by in vitro blastogenesis. A comparison of responders to nonresponders revealed a significant difference in mean B. pahangi reactivity (15,822 vs. 4,538 cpm, P less than 0.001), but no significant differences with respect to age, microfilaremia, PPD or PHA reactivity, or B. pahangi-specific antibody levels. Subtle differences may exist between these groups with respect to recognition of specific antigens on Western blots.
Assuntos
Antígenos de Helmintos/imunologia , Brugia/imunologia , Filariose Linfática/imunologia , Filariose/imunologia , Leucócitos Mononucleares/imunologia , Animais , Anticorpos Anti-Helmínticos/biossíntese , Haiti , Humanos , Imunidade Celular , Ativação Linfocitária , Microfilárias/imunologia , Wuchereria bancrofti/imunologiaRESUMO
Sera from individuals in an area of Haiti endemic for Mansonella ozzardi were analyzed for reactivity to antigens of Brugia pahangi, Dirofilaria immitis, Mansonella llewellyni or Ascaris lumbricoides using either an enzyme-linked immunosorbent assay or an indirect immunofluorescent antibody test. IgM and IgG reactivity to all antigens was observed with sera from both microfilaremic and amicrofilaremic individuals when compared to reactivity of sera from individuals from nonendemic areas. Antibody reactivity to B. pahangi was greater than that to other antigens. IgG reactivity of sera from endemic patients to filarial antigens was consistently greater than that of IgM. Antibody reactivity was not correlated with age or microfilarial density.
Assuntos
Anticorpos/imunologia , Antígenos de Helmintos/imunologia , Filarioidea/imunologia , Mansonella/imunologia , Animais , Anticorpos/análise , Antígenos de Helmintos/análise , Ascaris/imunologia , Brugia/imunologia , Dirofilaria immitis/imunologia , Cães/parasitologia , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Gerbillinae/parasitologia , Haiti , Humanos , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Imunoglobulina M/análise , Imunoglobulina M/imunologia , Mansonelose/imunologia , Mansonelose/parasitologia , Guaxinins/parasitologiaRESUMO
To determine the susceptibility of a heterologous filarial antigen for measuring Onchocerca volvulus antibodies, worms were compared using an enzyme-linked immunosorbent assay (ELISA) test. Control serum samples from helminth-free U.S. residents and from helminth-infected but filariae-free Salvadoran residents were tested and compared with serum obtained from microfilariae-positive and -negative Guatemalan residents living in an area of endemic onchocerciasis. The results showed that none of the sera from U.S. residents had positive O. volvulus ELISA titers (greater than or equal to 1:160); however, 8.51% (4/47) had positive B. malayi ELISA titers (greater than or equal to 1:640). The geometric mean titers with the B. malayi ELISA test were higher than with the O. volvulus ELISA test--in sera from 47 U.S. residents (1:219 vs. 1:49), from 108 Salvadoran residents (1:92 vs. 1:71), and from 145 microfilariae-negative (1:539 vs. 1:167) and 303 microfilariae-positive (1:1,270 vs. 1:561) Guatemalan residents. The B. malayi ELISA test exhibited slightly less sensitivity than the homologous O. volvulus ELISA test; nevertheless, a good correlation (r = 0.74) was found between the 2 test antigens, indicating that the B. malayi antigen could be used to measure O. volvulus antibodies.