Cesbron JY et al. (1988) J Immunol "Onchocerca volvulus. Monoclonal anti-idiotype antibody as antigen signal for the microfilaricidal cytotoxicity of diethylcarbamazine-treated platelets."

Cesbron JY, Hayasaki M, Capron A, Lutsch C, Grzych JM, Joseph M

[J Immunol, 1988]

Over the past 35 yr, diethylcarbamazine (DEC) has been the most widely used agent for the treatment of filarial diseases, particularly in onchocerciasis. The microfilaricidal action of DEC has been recently shown to be mediated by blood platelets with the additional triggering of a filarial excretory Ag (FEA). This FEA could be detected by using mAb in the serum of infected patients. By using one mAb (IA2(23] directed against Onchocerca volvulus and recognizing circulating Ag (Ab1), we purified by affinity chromatography the target molecule of IA2(23) (an O. volvulus glycoprotein recognized by IA2(23) mAb). This compound had a dose-dependent effect on the cytotoxic action of DEC-treated platelets. We subsequently produced an anti-idiotype mAb to Ab1 (Ab2), and considered the possibility of replacing the O. volvulus glycoprotein recognized by IA2(23) mAb by Ab2. Ab2 was selected according to its ability to inhibit the binding of radioiodinated Ab1 to the filarial target Ag. It induced the production of anti-O. volvulus antibodies (Ab3) in rats. At a constant concentration of DEC platelets, the addition of increasing amounts of Ab2 led to a dose-dependent cytotoxic effect against parasite larvae. Experiments performed with Ab2 on detergent solubilized surface proteins of platelets identified four bands of Mr 18, 26, 43.5, and 100 kDa, supporting the idea of the presence of binding sites on the platelets for a FEA required for the microfilaricidal cytotoxicity of DEC-treated platelets.

Lutsch C et al. (1987) Parasitol Res "Detection of circulating and urinary antigens in Mastomys natalensis experimentally infected with Brugia malayi, Brugia pahangi, or Litomosoides carinii."

Lutsch C, Zahner H, Capron A, Cesbron JY

[Parasitol Res, 1987]

The time-course of the detection of circulating and urinary filarial antigens was followed with a 2S-IRMA assay, using a mouse monoclonal antibody raised against Brugia malayi larvae, in Mastomys natalensis experimentally infected with Brugia malayi, Brugia pahangi, or Litomosoides carinii. In the prepatent phase of the infections, filarial antigen was detected 4-7 weeks before microfilariae appeared in the peripheral blood. Moreover, the sensitivity of the test was greater with urine than with serum. During the patent phase of infection, the level of circulating antigens detected varied considerably. However, there was a positive correlation (P less than 0.05) between antigenemia and microfilaremia. In L. carinii infection, filarial antigen could be easily detected in spite of the disappearance of microfilariae in peripheral blood, 49 weeks post infection. If these results are extrapolated to man, the 2S-IRMA should be useful for epidemiological surveys in endemic areas where transmission has been eliminated.

Magnusson CG et al. (1986) Int Arch Allergy Appl Immunol "Raised serum IgG4 levels in patients with atopy and filariasis: application of an automated particle-counting immunoassay using monoclonal antibody."

Cesbron JY, Djurup R, Magnusson CG, Capron A, Johansson SG

[Int Arch Allergy Appl Immunol, 1986]

We show here an automated (50 samples/h) assay for serum IgG4 having a throughput time of 40 min per sample and a sensitivity of 10 micrograms/ml. The assay procedure is based on the inhibition by sample of the agglutination reaction between monoclonal anti-IgG4 antibodies and latex particles to which IgG4 myeloma protein has been coupled. Assay reliability was ascertained by testing for linearity, analytical recovery (96.4%), interassay precision (less than or equal to 8%), specificity and correlation between the results obtained with monoclonal and polyclonal anti-IgG4 antibodies (n = 84; rs = 0.97). Application of the assay to sera from various groups of patients indicated significantly (p less than 0.00005) higher geometrical means (Gx) in patients suffering from atopy (n = 87; Gx = 617 micrograms/ml), atopic dermatitis (n = 28; Gx = 1,043 micrograms/ml), filariasis with Onchocerca volvulus (n = 48; Gx = 1,681 micrograms/ml) and Brugia malayi (n = 20; Gx = 1,078 micrograms/ml) as compared to nonatopic subjects (n = 103; Gx = 302 micrograms/ml) and randomized paired maternal/cord sera (n = 41; Gx = 276 and 296 micrograms/ml, respectively). IgG4 in the paired maternal/cord sera correlated (r = 0.98; p less than 0.00005). There was no significant influence of age or sex on the IgG4 levels either among the nonatopics or the atopics even though low IgG4 (less than or equal to 30 micrograms/ml) was more common among women. The results suggest that IgG4 and IgE responses are somehow closely related in atopic and parasite-infested patients at the physiological, pathogenic or genetic level.

Pancre V et al. (1988) Int Arch Allergy Appl Immunol "IgE-dependent killing of Brugia malayi microfilariae by human platelets and its modulation by T cell products."

Capron A, Cesbron JY, Joseph M, Auriault C, Pancre V, Chandenier J

[Int Arch Allergy Appl Immunol, 1988]

Platelets isolated from patients infected with filariasis were cytotoxic for microfilariae in vitro. Moreover, platelets from normal donors acquired killing properties in the presence of serum from infected individuals. The humoral factor involved in this cytotoxic process was shown to be IgE. This IgE-dependent cytotoxicity of platelets was strongly inhibited by antigen-stimulated T lymphocyte supernatants from filarial patients.