Isolation and characterization of expression cDNA clones encoding antigens of Onchocerca volvulus infective larvae.

Unnasch, Thomas R.; Gallin, Michaela Y.; Soboslay, Peter T.; Erttmann, Klaus D.; Greene, Bruce M.

doi:10.1172/jci113581

Cited by 72 publications

(21 citation statements)

References 27 publications

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“…Alternatively, autoreactive T cells or B cells could directly be activated by parasite antigens crossreactive with human defensin. Crossreactivity cannot be ruled out at present, particularly as O volvulus antigens that are cross-reactive with other human proteins have been detected (24)(25)(26). The second mechanism of T cell help would involve activation of T cells reactive with conjugates between human defensin and onchocercal antigens.…”

Section: A X Y X R I P a X I A G E R R Y G T X I Y Q A C Y C R I P A mentioning

confidence: 99%

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

Gallin

Jacobi

Büttner

et al. 1995

The Journal of Experimental Medicine

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SummaryChronic hyperreactive onchodermatitis (sowda) is a severe form of onchocerciasis observed in a subset of individuals infected with the filarial nematode Onchocerca volvuhs. SDS-PAGE and immunoblot analyses of Q 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. Microftlaricidal 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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Section: A X Y X R I P a X I A G E R R Y G T X I Y Q A C Y C R I P A mentioning

confidence: 99%

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

Gallin

Jacobi

Büttner

et al. 1995

The Journal of Experimental Medicine

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“…Several observations provide evidence that CRT can be the target of protective immunity. Homologues of CRT which show between 50% and 60% amino acid identity to human CRT have been found in the human parasites Onchocerca volvulus [9] and Schistosoma mansoni [10], which may help explain why CRT is a target for autoimmunity. CRT is normally intracellular, but has been found expressed on the surface of lung fibroblasts, with enhanced surface expression in response to cytomegalovirus infection [11].…”

Section: Introductionmentioning

confidence: 99%

The systemic lupus erythematosus (SLE) disease autoantigen—calreticulin can inhibit C1q association with immune complexes

Kishore

Sontheimer

Sastry

et al. 1997

Clinical and Experimental Immunology

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SUMMARYFollowing its release from cells during infection and inflammation, calreticulin (CRT) can act as an autoantigen in diseases such as SLE. Why CRT is a target of protective immunity and whether it may interfere with innate immunity once released from cells during inflammation is unclear. In the present study, we found that CRT was detected more frequently in SLE sera and in higher amounts than found in control sera. Approximately 40% of SLE sera tested contained autoantibodies against CRT as detected by ELISA and immunoblotting. CRT was found to be predominantly in the sera of SLE patients associated with immune complexes and C1q, and only bound to the surfaces of neutrophils in the presence of low levels of calcium and magnesium. In order to further investigate the C1q-CRT interaction, recombinant CRT and its discrete domains (N-, P-, and C-domains) were produced in Escherichia coli. CRT binds to globular head region of C1q primarily via its N-and P-domains. The N-domain was shown to be the most autoantigenic region of CRT, as the anti-CRT autoantibodies from most patients reacted against this region. CRT also altered C1q-mediated immune functions. The P-domain of CRT bound to C1q and reduced the binding of immune complexes in SLE sera to immobilized C1q. Full length CRT and its N-and P-domains were able to reduce the C1q-dependent binding of immune complexes to neutrophils and solid-phase bound C1q. We conclude that CRT, once released from leucocytes during inflammation, may not only induce an antigenic reaction, but also interfere with C1q-mediated inflammatory processes.

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“…However, eradication of the adult O. volvulus within the human population is unlikely to be achieved by these means [1]. In order to identify potential vaccine candidates, the serological recognition of parasite antigens by putatively resistant as well as susceptible individuals has been comparatively examined [10], or else recombinant antigens that elicit cellular immune responsiveness have been identified [11][12][13]. In the present study we have extended these approaches and differentially investigated the in vitro cellular reactivity and cytokine production in response to crude and size-fractionated OvAg displayed by onchocerciasis patients and mf-negative and asymptomatic endemic normals.…”

Section: Introductionmentioning

confidence: 99%

“…Efforts to identify and characterize O. volvulus antigens involved in T cell activation have been restricted to using recombinant polypeptides [11][12][13]. However, post-translational modifications, e.g.…”

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confidence: 99%

Immunoregulation in onchocerciasis: predominance of Th1-type responsiveness to low molecular weight antigens of Onchocerca volvulus in exposed individuals without microfilaridermia and clinical disease

Lüder

Schulz‐Key

Banla³

et al. 1996

Clinical and Experimental Immunology

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SUMMARYChronic and generalized onchocerciasis is associated with suppression of the parasite-specific cellular responsiveness, while exposed individuals without parasitological and clinical evidence of infection (endemic normals) display prominent cellular reactivity to Onchocerca volvulus antigens (OvAg). In order to identify those parasite antigens which may account for this differential cellular responsiveness, total adult worm-derived OvAg were fractionated by means of preparative SDS-PAGE and blot-elution into 22 antigen fractions of continuously decreasing molecular weight. Peripheral blood mononuclear cells (PBMC) from microfilariae (mf)-positive onchocerciasis patients (n 18) proliferated weakly in response to all OvAg fractions. In contrast, in vitro reactivity of PBMC from endemic normals (n 9) was depressed in response to OvAg of mol. wt 200-30 kD only, while antigens of mol. wt <30 kD induced vigorous proliferation in these individuals compared with the microfilaridermic patients (P < 0 . 05). Highest proliferative reactivity of cells from endemic normals was observed in response to OvAg of mol. wt 15-11 kD. Furthermore, these low mol. wt antigen fractions induced substantial production of IL-2 and interferon-gamma (IFN-°) in PBMC from endemic normals, but not in those from onchocerciasis patients. Cells from individuals of both groups secreted similar amounts of IL-5 in response to all OvAg fractions, with highest production again being induced by low mol. wt OvAg. In contrast, PBMC from onchocerciasis patients clearly produced more IL-10 than did cells from endemic normals. This augmented IL-10 production by PBMC from mf-positive individuals was not only observed after stimulation with OvAg fractions, but was measured in unstimulated control cultures as well. IFN-°-specific mRNA in antigen-stimulated PBMC from endemic normals appeared to be more prominent than in cells from onchocerciasis patients. However, mRNA transcripts of IL-10 and IL-13 were clearly present in patients, but were absent or inconsistently observed in endemic normals. Our results suggest that vigorous Th1-type cellular responsiveness encountered in endemic normals is restricted to low mol. wt antigens of O. volvulus, while such reactivity will not be present in mf-positive individuals. Furthermore, spontaneous production of high levels of IL-10 in onchocerciasis patients is likely to suppress Th1-type immunity, and thus may favour manifestation of chronic onchocerciasis. These traits of cellular immunity may contribute to the differential outcome of O. volvulus infection, the manifestation of clinical disease, and may also regulate the build up of acquired immunity in humans.

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Isolation and characterization of expression cDNA clones encoding antigens of Onchocerca volvulus infective larvae.

Cited by 72 publications

References 27 publications

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

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

The systemic lupus erythematosus (SLE) disease autoantigen—calreticulin can inhibit C1q association with immune complexes

Immunoregulation in onchocerciasis: predominance of Th1-type responsiveness to low molecular weight antigens of Onchocerca volvulus in exposed individuals without microfilaridermia and clinical disease

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