HUMAN AUTOANTIBODY TO DEFENSIN - DISEASE ASSOCIATION WITH HYPERREACTIVE ONCHOCERCIASIS (SOWDA)

Chronic hyperreactive onchodermatitis (sowda) is a severe form of onch ocerciasis observed in a subset of individuals infected with the filar ial 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 st udied. In comparison, only 7 of 44 (16%) patients with generalized onc hocerciasis and 11 of 21 (52%) of exposed individuals with no microfil ariae 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 disappearanc e of antibodies to the 2.5-kD antigen. Amino acid sequencing of the an tigen indicated identity to human defensins 1-3 of neutrophils. Defens in was demonstrated by immunohistochemical staining in onchocercal nod ules on the surface of adult filariae and in the surrounding tissue. A similar staining pattern was observed for other proteins present in n eutrophils such as myeloperoxidase, elastase, and the L-1 protein comp lex (MRP 8/MRP 14), indicating that neutrophils, macrophages, and thei r proteins predominate in the environment adjacent to the worms. These results demonstrate an association between the presence of autoantibo dies to defensins and an infectious disease of known etiology. The ass ociation with a particular form of onchocerciasis, sowda, suggests a l ink between formation of autoantibodies to defensin and enhanced immun e reactivity towards the parasite.