Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The full length cDNA of the immunodominant Ov33 protein of Onchocerca volvulus was expressed in E. coli using various vector constructs. Expression was best with the vectors pGEX2T and pCG808fx, yielding fusion protein Ov33-GST and Ov33-MBP, respectively. Purified fusion protein Ov33-GST and O. volvulus antigen extracts (OvAg) were used to compare antibody responses (IgM and IgG-subclasses) of patients infected with O. volvulus, Brugia malayi, Wuchereria bancrofti, Mansonella perstans/Loa loa and of Sudanese control sera. Sera of all groups contained IgM reacting with Ov33-GST and with OvAg. There was no IgG1 response to Ov33-GST. IgG1 responses to OvAg were only detected in filariasis sera. IgG2 and IgG3 responses were not detectable or marginal in all groups. The IgG4 reaction of onchocerciasis patients to Ov33-GST and to OvAg was high, whereas few other filariasis sera contained IgG4 antibodies to Ov33-GST and to OvAg. A serodiagnostic test for onchocerciasis based on detection of IgG4 to Ov33-GST had a sensitivity of 93.3% and a specificity of 96%. An epitope common to Ov33 and to the homologous proteins of other filarial species was demonstrated with a monoclonal antibody. Purified Ov33-MBP fusion protein was used to follow the development of the antibody response of four chimpanzees experimentally infected with O. volvulus. The data indicates that antibodies to Ov33 are induced by developing worms and later parasite stages.
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PMID:Specific and sensitive IgG4 immunodiagnosis of onchocerciasis with a recombinant 33 kD Onchocerca volvulus protein (Ov33). 128 26

In this study Onchocerca gutturosa was compared with O. volvulus in an ELISA test to detect Onchocerca-specific IgG and IgG subclasses. The test was developed and standardized to detect Onchocerca-specific IgG and IgG subclasses in sera of onchocerciasis patients and endemic controls. Onchocerca volvulus and O. gutturosa crude water-soluble antigens showed no significant difference in detecting onchocerca-specific IgG antibody (T = 1.88, P greater than 0.05). The levels of IgG subclasses varied greatly. IgG4 showed the highest detected mean level (0.84 +/- 0.59) and the other three subclasses showed considerably lower mean levels (IgG1 = 0.27 +/- 0.16, IgG2 = 0.24 +/- 0.17, IgG3 = 0.28 +/- 0.12). The status and score of skin lesions were found to have significant effect on the IgG and IgG subclasses levels (all P less than 0.001). IgG4 showed a positive correlation with the microfilarial (Mf) load (r = 0.21, P less than 0.03). IgG3 levels have a significant negative correlation with the Mf load (r = -0.23, P less than 0.02). The biological significance of these IgG and IgG subclasses in onchocerciasis is discussed.
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PMID:The profile of IgG and IgG subclasses of onchocerciasis patients. 157 89

To examine the fine specificity of the human immune response to filarial paramyosin, the antigenicity of an expressed rcDNA (2.55 kb) of Dirofilaria immitis paramyosin was detailed by ELISA. Using sera from patients infected with Onchocerca volvulus, we analyzed both the entire paramyosin molecule and six subcloned fragments for their IgG, IgG subclasses, and IgE responses. Patients from both Guatemala (64% positive) and Ghana (100% positive) reacted to paramyosin with specific IgG levels above normal controls. Although there was no anti-paramyosin subclass restriction common to all patients, the IgG3 response in the Ghananians was significantly greater than that of Guatemalans (p less than 0.001). IgE anti-paramyosin responses showed positive correlations with IgG2 (p less than 0.001), IgG4 (p less than 0.002), and IgG1 (p less than 0.04) responses. Epitope mapping using the IgG response to the six subclones demonstrated preferential recognition of the amino terminal end of the molecule (nucleotides 1 to 360). IgG2 reactivity was clearly localized to the most amino-terminal 120 amino acids, and the IgG4 antibodies recognized amino acids immediately adjacent to this fragment. These studies examining the fine specificity of anti-filarial immune reactions should provide a method for understanding how parasites either evade or induce host immune responses.
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PMID:B cell responses to paramyosin. Isotypic analysis and epitope mapping of filarial paramyosin in patients with onchocerciasis. 170 Oct 1

The population from five Guatemalan plantations in areas endemic for onchocerciasis was surveyed, and 1032 individuals were recruited to participate in our study. From physical examination, past clinical history (5 to 8 yr), laboratory evidence and sample availability, a group of 778 long term residents with confirmed disease status were selected for detailed examination. We were able to identify 268 long term residents of endemic areas who had never been infected, 44 of these are from hyper- and mesoendemic areas. The 44 uninfected individuals from the hyper- and mesoendemic areas, because of their considerable exposure to this disease, were classified as "putatively immune." Intact nodules containing adult worms of Onchocerca volvulus were homogenized in the presence of protease inhibitors and fractionated into particulate and aqueous isotonic soluble antigens. Systematic analysis of these Ag fractions showed considerable amounts of Ig, presumably associated with Ag in the form of immune complexes. Individual specific antibody reactions from all 778 patients to nodule Ag were examined. Reactions to O. volvulus antigens by antibodies from patients with confirmed parasitic infections were almost exclusively restricted to IgG1 and IgG4 isotypes. Antigenic activity appeared to be primarily associated with low molecular mass (14 to 29 kDa) components. Some competitive blocking of antibody activities of other isotypes by IgG1 was observed, most notable was that of IgG3 and IgA. IgG4 and IgM activities were not significantly blocked.
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PMID:Guatemalan human onchocerciasis. I. Systematic analysis of patient populations, nodular antigens, and specific isotypic reactions. 203 67

Ag-specific isotypic differences in immune response to Onchocerca volvulus Ag were assessed for 778 long term residents of endemic Guatemalan areas by quantitative ELISA with 5-min incubation steps and immunoblot. The study population was separated into five groups based on clinical status: N+F+, N+F-, N-F+, N-F-H+, and N-F-H-, where N = O. volvulus adults (nodule), F = microfiladermia, and H = history of O. volvulus infection. A subset of 44 individuals with high exposure to onchocerciasis from the N-F-H- group were critically evaluated and designated as "putatively immune." IgG1 reactivity to O. volvulus Ag was elevated in the majority of infected persons, but not in putatively immune individuals. Specific IgG3 levels, however, were equally elevated in all groups. The majority of N+F- persons also had elevated IgG1 levels, but they were lower than those found in F+ persons. IgG3 reactivities to a group of antigens at 20 kDa (GP20) were seen in many uninfected persons and some N+F- persons. In contrast, most F+ persons, react to this Ag with IgG1 and not IgG3. A mangabey inoculated with the infectious larval stage of O. volvulus (L3), but showed no signs of infection, began to recognize GP20 at 2 wk postinoculation. Early recognition of GP20 was possibly elicited by the larval stage. Purified nodule Ag from N+F+ individuals contained GP20, however, identical nodule Ag prepared from N+F- individuals did not. These data suggest that GP20 Ag may be common to both uterine microfilaria and the infectious larval stages. The fact that GP20 is predominantly recognized by IgG3 in putatively immune persons and some N+F- persons suggests that this increased IgG3 activity may be important in acquired immunity to onchocerciasis.
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PMID:Guatemalan human onchocerciasis. II. Evidence for IgG3 involvement in acquired immunity to Onchocerca volvulus and identification of possible immune-associated antigens. 203 68

Somatic antigens of Loa loa adult worms with molecular weights of 15-180 kDa were identified by Western blot analysis using sera from 3 categories of parasitologically and clinically defined subjects from a loiasis endemic zone. Sera of occult, amicrofilaremic (OL), and 'resistant' individuals with no clinical signs of infection (R) reacted with an antigen of 160 kDa; sera of highly microfilaremic individuals (ML) did not. ML sera strongly reacted with an antigen of 18 kDa which was recognized only weakly or not at all by OL and R sera. At higher dilutions, OL sera only reacted with antigens at 23 and 160 kDa and ML sera reacted with antigens at 18 and 23 kDa, whereas R sera reacted with antigens at 23, 42, 54, 70, 100, and 160 kDa. These data suggested that R sera contained a higher concentration of antibodies which reacted with denatured, nitrocellulose-bound antigens. The IgG4 isotype predominated for all groups of sera, while IgG3 antibody responses were observed only with R sera. IgG1 antibodies were seen in all groups but reacted with fewer antigens than IgG4 antibodies, and no IgG2 antibody responses were detected. Sera against Brugia malayi, Wuchereria bancrofti, Onchocerca volvulus, and Dirofilaria immitis cross-reacted with somatic antigens greater than 70 kDa, whereas none reacted with Loa loa antigens less than 23 kDa.
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PMID:Differential recognition of Loa loa antigens by sera of human subjects from a loiasis endemic zone. 264 44

Individual human Ig class responses to Onchocerca volvulus antigens have been evaluated by Western blotting using sera from cases of generalized onchocerciasis and chronic hyper-reactive onchocerciasis (Sowda). in all cases except IgG3 the patterns of recognition by human antibody classes were similar in Sowda and generalized onchocerciasis. Weak or undetectable responses were seen with IgG1, IgG2 and IgM. The total profiles of antigens recognized by the other Ig classes were different, although in some cases certain bands were commonly identified. The result with IgG3, however, was striking. Here, two major antigens (9 kD and 72kD) were recognized by IgG3 antibodies in Sowda sera but not generalized onchocerciasis sera. Furthermore, these two antigens were not recognised by any other Ig class, either in generalized or Sowda onchocerciasis, nor were they detected by antibodies of any class present in a collection of sera representative of other nematode infections. This difference in the IgG3 response was so pronounced that Sowda sera could be distinguished from generalized onchocerciasis sera by an IgG3-specific ELISA assay with a PBS parasite extract as the antigen. Thus, a correlation has been established between one particular clinical condition of onchocerciasis (Sowda) and a serological response, defined in terms of both the parasite antigens and an immunoglobulin class restricted antibody response.
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PMID:Unique recognition of a low molecular weight Onchocerca volvulus antigen by IgG3 antibodies in chronic hyper-reactive oncho-dermatitis (Sowda). 322 41

Characterization of the immune response to Onchocerca volvulus is important for the diagnosis, control and understanding of the disease it causes. The antibody response to surface, secreted and somatic antigens of the worm has therefore been examined at an individual immunoglobulin (Ig) class level, by using a panel of different human sera. Onchocerca-specific antigens tend to be of low molecular mass and preferentially recognized by IgG4 and IgE. There is considerable cross-reaction between O. volvulus and O. gibsoni, so that the latter may be an alternative source of material for use in diagnosis. A surface-enriched fraction of low molecular mass appears to be a most promising diagnostic tool. Amongst somatic antigens, two were uniquely recognized by IgG3 antibodies in sera from sowda patients, thereby providing a molecular correlate for a recognized pathological condition. Improved diagnosis is needed for detecting infection in both humans and the vector. Our target for detection in humans is a continuously released, nonimmunogenic product, which is ideally stage and parasite specific. The excretions of adult worms do contain components not recognized by antibodies in infected serum, but we cannot rule out that these are of host, rather than parasite origin. Excretions of Litomosoides carinii contain both host and parasite molecules and, in addition, stage-specific and sex-specific components. Unfortunately, however, the rate of production of excretions varies during the life of L. carinii. This finding may be relevant to the detection of Onchocerca excretions if they are produced at a similarly uneven rate. Finally, for detecting infective larvae in the vectors, we are currently screening a genomic library of O. volvulus for an appropriate probe. To date, one DNA sequence has been cloned that shows promising specificity.
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PMID:Onchocerca antigens in protection, diagnosis and pathology. 329 54

Persons exposed to Onchocerca volvulus express differences in manifestations of onchocerciasis ranging from hyporeactive (generalized) to hyperreactive (sowdah) forms; absence of disease is seen in endemic normal persons. Analysis of the IgG isotypic antibody response to O. volvulus extracts and nonparasite ubiquitous antigens in 92 West Africans revealed highest anti-O. volvulus IgG1 and IgG2 responses in sowdah, high levels in the generalized form, and low antibody levels in endemic normal persons. Nonexposed persons had no antibodies. A significant IgG3 antibody response was detected only in sowdah, while high IgG4 levels occurred in both polar groups but were absent in both control groups. Isotypic responses to antigens unrelated to O. volvulus were similar in all groups but showed higher IgG1 and IgG2 levels in sowdah. Sowdah patients had high levels of Ro/SS-A antibodies, circulating immune complexes, and eosinophil cationic protein. These results document a strong B cell response in African sowdah and indicate variations in immune responsiveness.
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PMID:Strong IgG isotypic antibody response in sowdah type onchocerciasis. 793 Jul 41

The existence of immunity to Onchocerca volvulus (Ov) infection is suggested by the presence of uninfected persons in hyperendemic areas. A major barrier to the study of immunity has been the correct identification of putatively immune (PI) subjects. To identify a PI group in a hyperendemic area in Ecuador, clinical and epidemiologic information was combined with a polymerase chain reaction (PCR)-based assay identifying Ov DNA in skin snips and a recombinant antigen-based ELISA. Comparison of immune responses revealed that PI subjects had significantly lower levels of Ov-specific IgG, IgG subclasses, and IgE than infected (INF) subjects. Female subjects were significantly more likely to be PI than male subjects, and INF female subjects had significantly lower levels of Ov-specific IgG, IgG1, and IgG3 than INF male subjects. Thus, the use of molecular-based techniques has helped to define more precisely the PI state in onchocerciasis.
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PMID:Immunity to onchocerciasis: identification of a putatively immune population in a hyperendemic area of Ecuador. 793 Jul 13


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