Human autoantibody to defensin: disease association with hyperreactive onchocerciasis (sowda)

Chronic hyperreactive onchodermatitis (sowda) is a severe form of onchocerciasis observed in a subset of individuals infected with the filarial nematode Onchocerca volvulus. SDS-PAGE and immunoblot analyses of O. volvulus adult worm extracts were used to characterize the antigens of the marked antib...

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Veröffentlicht in:The Journal of experimental medicine 1995-07, Vol.182 (1), p.41-47
Hauptverfasser: Gallin, M Y, Jacobi, A B, Büttner, D W, Schönberger, O, Marti, T, Erttmann, K D
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creator Gallin, M Y
Jacobi, A B
Büttner, D W
Schönberger, O
Marti, T
Erttmann, K D
description Chronic hyperreactive onchodermatitis (sowda) is a severe form of onchocerciasis observed in a subset of individuals infected with the filarial nematode Onchocerca volvulus. SDS-PAGE and immunoblot analyses of O. volvulus adult worm extracts were used to characterize the antigens of the marked antibody response of sowda patients. One 2.5-kD antigen was recognized by sera from all 35(100%) sowda patients that were studied. In comparison, only 7 of 44 (16%) patients with generalized onchocerciasis and 11 of 21 (52%) of exposed individuals with no microfilariae in skin snips and no signs of disease showed reactivity to this antigen. Microfilaricidal treatment of sowda patients with improvement of the clinical status was associated with a decrease or disappearance of antibodies to the 2.5-kD antigen. Amino acid sequencing of the antigen indicated identity to human defensins 1-3 of neutrophils. Defensin was demonstrated by immunohistochemical staining in onchocercal nodules on the surface of adult filariae and in the surrounding tissue. A similar staining pattern was observed for other proteins present in neutrophils such as myeloperoxidase, elastase, and the L-1 protein complex (MRP 8/MRP 14), indicating that neutrophils, macrophages, and their proteins predominate in the environment adjacent to the worms. These results demonstrate an association between the presence of autoantibodies to defensins and an infectious disease of known etiology. The association with a particular form of onchocerciasis, sowda, suggests a link between formation of autoantibodies to defensin and enhanced immune reactivity towards the parasite.
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SDS-PAGE and immunoblot analyses of O. volvulus adult worm extracts were used to characterize the antigens of the marked antibody response of sowda patients. One 2.5-kD antigen was recognized by sera from all 35(100%) sowda patients that were studied. In comparison, only 7 of 44 (16%) patients with generalized onchocerciasis and 11 of 21 (52%) of exposed individuals with no microfilariae in skin snips and no signs of disease showed reactivity to this antigen. Microfilaricidal treatment of sowda patients with improvement of the clinical status was associated with a decrease or disappearance of antibodies to the 2.5-kD antigen. Amino acid sequencing of the antigen indicated identity to human defensins 1-3 of neutrophils. Defensin was demonstrated by immunohistochemical staining in onchocercal nodules on the surface of adult filariae and in the surrounding tissue. 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subjects Adolescent
Adult
Aged
Amino Acid Sequence
Animals
Antibodies, Helminth - analysis
Antigens, Helminth - chemistry
Antigens, Helminth - immunology
Autoantibodies - immunology
Autoantigens - chemistry
Autoantigens - immunology
Autoimmune Diseases - etiology
Autoimmune Diseases - immunology
Autoimmune Diseases - parasitology
Blood Proteins - chemistry
Blood Proteins - immunology
Child
Child, Preschool
Chronic Disease
Cross Reactions
Defensins
Dermatitis - etiology
Dermatitis - immunology
Dermatitis - parasitology
Female
Humans
Male
Microfilariae - isolation & purification
Middle Aged
Molecular Mimicry
Molecular Sequence Data
Neutrophils - chemistry
Neutrophils - immunology
Onchocerca volvulus
Onchocerca volvulus - immunology
Onchocerca volvulus - isolation & purification
Onchocerciasis - complications
Onchocerciasis - immunology
Sequence Homology, Amino Acid
Skin - parasitology
title Human autoantibody to defensin: disease association with hyperreactive onchocerciasis (sowda)
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