Piessens WF et al. Nature "Diethylcarbamazine enhances antibody-mediated cellular adherence to Brugia malayi microfilariae."

Beldekas M, Piessens WF

[Nature]

Treatment with the antifilarial drug diethylcarbamazine (DEC) results in a rapid decline in the number of microfilariae circulating in the blood of infected hosts. DEC induces morphological changes in the surface layers of microfilariae, but these alterations alone are probably insufficient to cause the death of the parasite, because the drug fails to reduce microfilaraemia in animals lacking filarial antibodies, and also does not shorten the survival of microfilariae in vitro. The effect of DEC in vivo is thought to result from the trapping of microfilariae in the liver, where they undergo lysis.

Piessens WF et al. (1981) Acta Trop "Effect of treatment with diethylcarbamazine on immune responses to filarial antigens in patients infected with Brugia malayi."

Piessens WF, Koiman I, Darwis F, McGreevy PB, Dennis DT, Piessens PW, Palmieri JR, Ratiwayanto S, Tuti S

[Acta Trop, 1981]

We studied the effect of treatment with diethylcarbamazine (DEC) on immune responses to parasite antigens in humans infected with Brugia malayi. In vitro lymphocyte proliferative responses to microfilarial antigens increased in patients who became amicrofilaremic after treatment with DEC. No changes in reactivity were observed in amicrofilaremic individuals who were given DEC or in a small number of patients who remained microfilaremic after treatment. Reactions to other antigens (PPD and SKSD) were not affected by drug treatment. Serum titers of antibodies to the sheath of B. malayi microfilariae did not significantly change during the period of observation. These findings indicate that DEC partially reverses the state of cellular unresponsiveness to parasite antigens associated with patient filarial infections.

Piessens WF et al. (1982) N Engl J Med "Antigen-specific suppressor T lymphocytes in human lymphatic filariasis."

Dennis DT, Palmieri JR, Koiman I, Partono F, Piessens WF, Carney WP, Hoffman SL, Ratiwayanto S, Piessens PW

[N Engl J Med, 1982]

Immune responses to parasite antigens are much lower in patients with microfilaremia than in persons with other manifestations of brugian filariasis. To determine whether hyporeactivity is associated with changes in populations of lymphocytes that regulate immune responses, we quantitated helper and suppressor T cells in the blood of patients infected with Brugia malayi. Increased numbers of suppressor T cells were present in 15 of 17 patients with microfilaremia and in six of 11 patients with elephantiasis. This increase correlated with hyporeactivity to filarial antigens but not to nonparasite antigens. Removal of suppressor T cells activated in vivo or in vitro improved reactivity to filarial antigens. These results suggest that immunosuppression induced by filarial parasites is a possible mechanism of survival of these organisms in an immunocompetent host.

Piessens WF et al. (1980) J Clin Invest "Immune responses in human infections with Brugia malayi: specific cellular unresponsiveness to filarial antigens."

McGreevy M, Dennis DT, McGreevy PB, Koiman I, Piessens WF, Piessens PW, Saroso JS

[J Clin Invest, 1980]

We evaluated the cellular immune competence of 101 subjects living in an area of South Kalimantan (Borneo) where Malayan filariasis is endemic. All patients with elephantiasis but none with other clinical stages of filariasis reacted with adult worm antigens. The majority of subjects without clinical or parasitological evidence of filariasis and approximately one-half of those with amicrofilaremic filariasis reacted with microfilarial antigens. In contrast, most patients with patent microfilaremia did not respond to microfilarial antigens. The in vitro reactivity of all patient categories to nonparasite antigens was similar to that of the distant control group. These results indicate that patent microfilaremia is associated with a state of specific cellular immune unresponsiveness and are consistent with the current hypothesis that the various clinical manifestations of filariasis result from different types of immune responses to distinct antigens associated with different developmental stages of filarial worms.

Piessens WF et al. (1980) N Engl J Med "Antigen-specific suppressor cells and suppressor factors in human filariasis with Brugia malayi."

Dennis DT, Ratiwayanto S, Piessens WF, Tuti S, Piessens PW, Koiman I, Palmieri JH

[N Engl J Med, 1980]

We investigated the mechanisms of specific immune unresponsiveness to microfilarial antigens. The blood of patients with obvious Brugia malayi infections contains an adherent cell type that specifically suppresses reactions to microfilarial antigens but not to other antigens. In the absence of continued stimulation by parasite antigens, this suppressor cell loses its functional activity after overnight culture in vitro. Furthermore, serums from patients with and without microfilaremia contain factors that also suppress reactions to filarial antigens in vitro. These results suggest that immune unresponsiveness in human beings with patent filarial infections is due to active suppression of immune responses directed against the parasite and not to an intrinsic inability of infected patients to react to parasite antigens.

Sritharan M et al. (1997) Mol Biochem Parasitol "Actin of Brugia malayi microfilariae contains a developmentally regulated antigenic epitope."

Piessens WF, Sritharan M

[Mol Biochem Parasitol, 1997]

Wadee AA et al. (1986) Am J Trop Med Hyg "Microfilariae of Brugia malayi contain a T cell mitogen."

Wadee AA, Piessens WF

[Am J Trop Med Hyg, 1986]

We investigated the mechanisms that lead to polyclonal hypergammaglobulinemia in persons exposed to or infected with lymph-dwelling filarial parasites. Extracts of microfilariae of Brugia malayi induce the in vitro proliferation of lymphocytes from nonsensitized donors. The mitogenic factor(s) responsible for this effect is of low molecular weight (Mr) and acts on T4+ cells but not on T8+ T lymphocytes or on B cells. T4+ lymphocytes stimulated with filarial mitogen augment the in vitro production of immunoglobulins by autologous B lymphocytes.

Dissanayake S et al. (1992) Mol Biochem Parasitol "Filarial parasites contain a ras homolog of the TC4/ran/Spil family."

Piessens WF, Xu M, Dissanayake S

[Mol Biochem Parasitol, 1992]

We have isolated and characterized a gene encoding a novel GTP-binding protein of the GTPase superfamily in the filarial parasites Brugia malayi and Onchocerca volvulus. The deduced amino acid sequence of the cloned molecule has approximately 30% overall homology to ras proteins and approximately 90% homology to the 'ras-like' nuclear proteins TC4, ran and Spil. Rabbit antisera to bacterially expressed filarial protein detect a 24-22 kDa doublet in extracts of adult B. malayi and mature microfilariae, which is absent from immature microfilariae. Increased expression of the native parasite protein occurs when worms are cultured in the presence of epidermal growth factor.

Petralanda I et al. (1988) Am J Trop Med Hyg "Parasite antigens are present in breast milk of women infected with Onchocerca volvulus."

Petralanda I, Yarzabal L, Piessens WF

[Am J Trop Med Hyg, 1988]

We used a noncompetitive two-site ELISA with 5 monoclonal antibodies to determine whether parasite antigens are present in breast milk from women infected with Onchocerca volvulus. Seven out of 13 available milk samples contained significant amounts of filarial antigens. Antigen indices in milk correlated with levels of microfilarodermia (Rs = 0.74, P less than 0.005). Antigen-containing milk samples markedly inhibited mitogen-induced proliferation of human mononuclear cells and activated cells within this population that suppressed the proliferative response of autologous lymphocytes to mitogens and antigens. These findings indicate that parasite products are present in breast milk of O. volvulus-infected women and suggest that these may induce immune tolerance and/or suppression in infants born of infected mothers.

Shah JS et al. (1987) Am J Trop Med Hyg "Characterization of an Onchocerca-specific DNA clone from Onchocerca volvulus."

Piessens WF, Karam M, Shah JS, Wirth DF

[Am J Trop Med Hyg, 1987]

A genomic library of a savanna isolate of Onchocerca volvulus was screened to detect recombinant plasmids containing highly repeated DNA sequences of this parasite. Four recombinant plasmids were identified which hybridized specifically to Onchocerca DNA, but not to DNA from humans, black flies, Brugia malayi, B. pahangi, or Wuchereria bancrofti. The recombinant plasmids had a low level of homology to Dirofilaria immitis. All recombinant plasmids contain related DNA sequences based on Southern hybridization analysis. Sequences related to these recombinant plasmids are present in different geographic isolates of O. volvulus and O. ochengi, an animal parasite. Two of the recombinant plasmids contain sequences also found in O. lienalis. One recombinant plasmid, puOvs3, has been characterized in detail, including DNA sequence determination. Radiolabeled puOvs3 is able to detect 100 pg of genomic DNA isolated from O. volvulus worms from both savanna and forest regions. It can differentiate O. volvulus from O. ochengi by Southern blot analysis.