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Biomedical subjects

L A Nilsson

Publications and source records attributed to L A Nilsson.

At least 19 recordsLinked to original sources

Association of -1087 IL10 and -308 TNFA gene polymorphisms with serological markers of coeliac disease.

Coeliac disease (CD) is known to have a strong genetic background. We analyzed the association between serological markers of CD and the -1087 IL10 and -308 TNFA gene polymorphisms in Swedish patients. A higher frequency of the TNF2 allele was present in the patients compared with the controls (p < 0.0001). The frequency of the AA genotype of the IL10 gene in the patients was unexpectedly higher in comparison with the controls (p < 0.05). The levels of IgA anti-endomysium and antitissue transglutaminase antibodies were associated with IL10 but not with TNFA genotype. The patients with the AA or GG -1087 IL10 genotypes had significantly lower levels of antibodies in comparison with those with the AG genotype (p < 0.05 to p < 0.0005). However, when divided according to potential level of IL-10 production, the group of potentially high IL-10 producers among the CD patients demonstrated significantly lower levels of antitissue transglutaminase antibodies compared to potentially low IL-10 producers (p = 0.01). Our results show a relationship between the levels of IgA antibodies involved in CD with the IL10 genotypes. This suggests a possible involvement of IL-10 in the development of the disease.

Alleles↗

Adult coeliac patients do tolerate large amounts of oats.

OBJECTIVE: The aim of the present study was to investigate whether adult patients with coeliac disease in remission could include large amounts of oats in their daily gluten-free diet for an extended period of time without adverse effects. DESIGN, SUBJECTS AND METHODS: Twenty adult coeliac patients in remission included large amounts of uncontaminated rolled oats in their daily diet for a prolonged period. The examinations, performed four times during the study period, included small bowel endoscopy with biopsies, blood samples (nutritional status, serological analysis), height and body weight, gastrointestinal symptoms and dietary records. Gastrointestinal symptoms and diet were also investigated through unannounced telephone interviews once a month during the study period. RESULTS: No adverse effects of a large intake of oats were seen in small bowel histology, serology nor in nutritional status in the 15 subjects who completed the whole study period. Two of the subjects dropped out because of gastrointestinal symptoms and three for non-medical reasons. The median intake of oats was 93 g/day and the compliance to the oat diet was found to be good. Examinations of the patients after drop-out did not show any deterioration in small bowel histology or nutritional status nor raised levels of antibodies. CONCLUSION: Results from this study indicate that adult patients with coeliac disease in remission can include large amounts of controlled wheat-free rolled oats for an extended period of time without adverse effects.

Adult↗

Role of immunosuppressive therapy in refractory sprue-like disease.

Patients with malabsorption and histological findings consistent with celiac disease, who are unresponsive to gluten free diet, and in whom other causes of flat mucosa have been excluded, are considered to suffer from so called unclassified or refractory sprue. Although the true nature of this condition needs to be further elucidated, it is known to represent a difficult therapeutical problem with potentially fatal course. Herein, we report a patient with refractory sprue-like disease who after failing to respond to corticosteroids and TPN was in a critical condition. He responded promptly to cyclosporine and made a remarkable recovery. In contrast to previous reports, the cyclosporine treatment in this patient was pursued only for 1 month, whereupon the patient turned responsive to steroids. Subsequent treatment with azathioprine allowed corticosteroids to be reduced to a low maintenance dose and eventually all drugs could be discontinued without reappearance of symptoms. Cyclosporine therapy might be lifesaving in occasional patients with refractory sprue-like disease and it may result in reversal of steroid resistance. Moreover, azathioprine seems to have a steroid sparing effect in this setting. Short term immunosuppressive treatment may have an advantage of lower risk for drug related side effects.

Azathioprine↗

Intranasal administration of Schistosoma mansoni adult worm antigen in combination with cholera toxin induces a Th2 cell response.

Mice immunized with soluble adult worm antigen (SWAP) in combination with cholera toxin (CT) displayed significantly larger numbers of IgG1, IgM and IgA secreting cells in the spleen and in the lungs as compared to mice which had received SWAP only. The ratio of SWAP-specific IgG1 to IgG2a antibody-secreting spleen cells was also significantly higher in the SWAP-CT group. Analysis of cytokine responses revealed that SWAP-stimulated spleen and lung cells from the SWAP-CT group produced lower levels of IFN-gamma but higher levels of IL-4 and IL-5 as compared to cells from the SWAP group. These findings indicate that intranasal administration of SWAP-CT induces a Th2 cell response in the spleen and in the lungs. Our findings also suggest that CT was responsible for induction of this Th2 cell response, since intranasal administration of SWAP alone induced a Th1 type response in the spleen and in the lungs.

Administration, Intranasal↗

Immunological cross reactivity between Schistosoma mansoni and cholera toxin.

Intranasal administration of schistosome antigens in combination with appropriate adjuvant may be an effective route for immunization against schistosomes, since the lungs represent an important site of elimination of schistosomulae. Our previous studies have shown that in mice intranasal administration of cholera toxin (CT) before infection with Schistosoma mansoni results in an enhancement of the worm burden in comparison to nontreated infected animals. In the present study, it was shown that mice treated intranasally with CT displayed high numbers of schistosome-reactive IgM-secreting cells in the spleen as well as high levels of schistosome-reactive serum IgM antibodies, whereas no significant immunological response against two other antigens, ovalbumin (OVA) or keyhole limpet haemocyanin (KLH) was noted. Sera from mice treated intranasally with CT recognized a 22 kDA antigen on SWAP blots. This band was not demonstrable after absorption of the sera with SWAP. These findings indicate a possible cross reactivity between cholera toxin and schistosome antigens. Further analysis by Western blot revealed that a 22 kDa antigen was detected on CT blots by sera from mice and humans infected with S. mansoni. This band was not demonstrable after absorption of the mouse or the human sera with CT. The 22 kDa cross reactive antigen was heat-stable. The antibodies against the 22 kDa antigen were only found within the IgM class but not within other Ig isotypes. Our findings also indicate that the 22 kDa antigen detected by anti-S. mansoni antibodies represents the A1 fragment of the cholera toxin.

Administration, Intranasal↗

Diagnosis of female genital schistosomiasis by indirect disease markers: determination of eosinophil cationic protein, neopterin and IgA in vaginal fluid and swab eluates.

Based on assumptions about the pathophysiology of egg-related lesions in the lower reproductive tract, putative indirect disease markers were investigated in vaginal fluids from 54 Malawi adolescent girls and women infected with S. haematobium. These women received a careful gynecological examination during which biopsies were taken from the cervix, and, if present, also from suspicious lesions in the vagina and the vulva. If the biopsies, either in wet crushed preparations or in histological sections, contained eggs the patients were considered to have female genital schistosomiasis (FGS; n = 33). The remainder (n = 21) were classified as having urinary schistosomiasis only. Eosinophil cationic protein (ECP), a cytotoxic granule protein of eosinophils, neopterin, a second messenger molecule generated during the activation of macrophages, and IgA as an indicator of local B-cell activation were quantitatively determined in vaginal fluid. To clarify the origin of ECP, this protein was also looked for in histological sections by an immunohistochemical method. In order to explore whether such disease markers can be detected after absorption to a tampon-like material, ECP and IgA were also assessed after elution from a non-porous, polypropylene fibre web impregnated with vaginal fluid. The concentration of ECP in vaginal fluid and the degree of immunohistochemical staining in histological sections were significantly higher in patients with FGS than in women with urinary schistosomiasis only. The amount of ECP detected in histological sections correlated to the number of eggs/mm2 of compressed genital tissue (rho = 0.36, P = 0.02), and the concentration of ECP in vaginal fluid correlated to the concentration of neopterin as well as to that of IgA (rho = 0.52, P = 0.004 and rho = 0.37, P = 0.02, respectively). Median neopterin concentration in vaginal fluid was also higher in the FGS group, but the difference was not statistically significant. ECP could also be detected in eluates from impregnated fibre webs, but the concentration was approximately one power of 10 less than in the original vaginal fluid. These results demonstrate that indicators of immunological mechanisms related to the egg-granuloma might be useful as indirect disease markers for women with FGS if assessed in vaginal washings or swab eluates.

Adolescent↗

A comparative study on specific antibodies and circulating antigen (CAA) in serum and parasitological findings for diagnosis of schistosomiasis mansoni in an endemic area in Tanzania.

A baseline study to evaluate the prevalence of Schistosoma mansoni infection as well as the diagnostic efficacy of serodiagnostic tests was performed in Kabaganga village, Kome island, Lake Victoria, Tanzania. A total of 1108 individuals were examined parasitologically and clinically. Egg excretion was demonstrated by one-sample Kato-Katz test. Specific IgG1 and IgG4 antibodies against S. mansoni adult worm (SAWA) and egg (SEA) antigens as well as circulating anodic antigen (CAA) were determined in serum samples from 250 of these subjects. As a control population 41 individuals from a non-endemic area were examined parasitologically, clinically and serologically. In the parasitologically examined Kabaganga population 45% were excreting eggs. The pattern of egg excretion was typical for an endemic area with a peak in the age group 10-14 years. Sixty-five percent of the serologically tested villagers were positive in the CAA test. A total of 80% were positive in either of the two tests, indicating an active infection. In 67-95% of these individuals the levels of isotype specific antibodies were increased. The prevalence of CAA positivity corresponded fairly well with that of Kato-Katz results in the age groups 10-29 years, but in the younger age groups a considerably greater number of individuals were positive in the CAA test than in the Kato-Katz test. The results obtained indicate that virtually all of the Kabaganga villagers, regardless of age, had an ongoing, active infection or had previously been infected with S. mansoni. This population, therefore, may be useful for evaluation of the diagnostic efficacy of various antibody tests. The highest degree of discrimination between the endemic and the non-endemic village populations was noted for anti-egg IgG4 antibodies. It is concluded that the combined determination of parasite eggs in faeces and CAA in serum provides high sensitivity as regards active infection. Increased levels of isotype-specific antibodies, particularly of the IgG4 subclass, is a sensitive indicator of past or present infection, and the prevalence of individuals with such increased levels may be a simple and reliable indicator of the frequency of schistosomiasis in a community.

Adolescent↗

Visceral leishmaniasis in Somalia. Significance of IgG subclasses and of IgE response.

We have determined the levels of IgG subclasses and IgE as well as specific antibodies of these isotypes in sera from 22 patients with clinical visceral leishmaniasis (VL) from Somalia. The results are compared with those obtained from 30 Somali and 23 Swedish controls. We found markedly increased concentrations of IgG1 in the VL sera, indicating that the pronounced increase in IgG in VL which is generally considered to be due to polyclonal B-cell activation is mainly restricted to this subclass. The IgG2 concentrations were significantly decreased. The IgG3 and IgG4 concentrations, on the other hand, did not differ between the two groups of Somali sera. The Somali control sera contained higher concentrations of IgG1 and IgG3, but significantly lower concentrations of IgG2 as compared to Swedish controls. The IgG4 values, on the other hand, were not different between the two groups of control sera. Anti-leishmania antibodies belonging to all IgG subclasses, were found in the patients' sera. There was no significant difference in total IgE between sera from VL patients and controls and specific IgE antibodies were only detected in a few patients. The Western blot assay (WB), revealed the presence of two bands corresponding to 74 kDa and 88 kDa in all patients' sera, indicating a possible diagnostic role for WB in this particular population.

Animals↗

Lack of interferon-gamma receptor does not influence the outcome of infection in murine schistosomiasis mansoni.

Studies of vaccine-induced immunity in experimental schistosomiasis in mice have suggested that interferon-gamma (IFN-gamma) is an important factor for the induction of protective immunity against schistosomiasis. The present study compares some parameters during primary schistosome infection in IFN-gamma receptor deficient mice and wild type mice. No significant difference in worm burden between the two groups was found. Almost the same number of eggs in the liver as well as typical granulomas with numerous macrophages and eosinophils were observed in both groups of mice. Furthermore, IFN-gamma receptor deficient mice infected with S. mansoni displayed a significant reduction in the number of IgG2a secreting cells in the spleen and a significant enhancement of IgA secreting cells in the spleen and in the lungs. These findings suggest that the lack of IFN-gamma activity may result in an enhanced dominance of Th2 cells which, however, does not influence the development of a primary schistosome infection.

Animals↗

Value of serologic markers for clinical diagnosis and population studies of coeliac disease.

BACKGROUND: There is a need for serologic markers in selecting patients with symptoms compatible with coeliac disease for intestinal biopsy and for population screening. Few comparative studies have been done. METHODS: Sera from 55 patients with coeliac disease and 65 referents, aged between 8 months and 79 years, were investigated. Anti-gliadin, anti-reticulin, anti-endomysium, and anti-jejunal antibodies were measured. The sensitivities, specificities, and positive predictive values for different disease prevalence levels were calculated. Confidence intervals, rarely used in this type of study, were calculated. RESULTS AND CONCLUSIONS: In most tests the antibody levels were age-correlated. The highest sensitivities in combination with high specificities were found for IgA anti-gliadin antibodies in children less than 5 years of age and IgA anti-endomysium antibodies in older children and adults. These tests were most useful for testing a population with a high disease prevalence, such as patients with gastrointestinal symptoms, although the results for many tests had overlapping confidence intervals. For screening unselected populations with a low disease prevalence, in which a test with maximum specificity is desired, only anti-endomysium antibodies had sufficiently high predictive value to be of practical use.

Adolescent↗

Campylobacter jejuni/coli and enterotoxigenic Escherichia coli (ETEC) in faeces from children and adults in Tanzania.

The occurrence of Campylobacter and enterotoxigenic E. coli (ETEC) was studied in faecal samples from Tanzanian children (< 5 years of age), adolescents and adults (only Campylobacter) with and without diarrhoea. The Campylobacter strains isolated were tested for subspecies, enterotoxigenicity and serotype. Out of 394 children with diarrhoea 18% were infected with Campylobacter and 20% with ETEC. In 278 samples tested for Campylobacter and 136 tested for ETEC from asymptomatic children the corresponding numbers were 12 and 5%, respectively. In children < 18 months with diarrhoea Campylobacter was noted in 22% and ETEC in 18%, whereas the figures were 11 and 4% respectively in asymptomatic children. In the age group 18 months to 5 years Campylobacter was demonstrated in 2% of the children with diarrhoea and 27% had ETEC, while the figures were 15 and 8% for asymptomatic children. Among adults the prevalence of Campylobacter-positive samples was 1% both for symptomatic and asymptomatic individuals. There were no seasonal differences in the prevalences of both Campylobacter and ETEC either in the symptomatic or the asymptomatic group. Campylobacter jejuni was the dominating Campylobacter species among both symptomatic and asymptomatic individuals. C. jejuni strains from patients with diarrhoea were significantly more often enterotoxigenic than were C. coli strains. The serotype pattern regarding Campylobacter was in general similar for symptomatic and asymptomatic individuals. We conclude that Campylobacter and ETEC are common causes of bacterial diarrhoea in Tanzanian children, and that Campylobacter infections are more important in children younger than 18 months, than in older ones.

Adolescent↗

Serum bactericidal activity and phagocytosis in host defence against Haemophilus ducreyi.

Serum bactericidal activity and phagocytic killing are two important mechanisms involved in the host defence against bacteria. Using some in vitro methods, serum bactericidal assay, phagocytic killing by polymorphonuclear leukocytes (PMN) and chemiluminescence, we have evaluated the significance of these mechanisms in the killing of Haemophilus ducreyi bacteria. Furthermore, induction of C3 conversion and deposition of immunoglobulins, C1q and C3, on the surface of bacteria was studied by crossed immunoelectrophoresis and ELISA, respectively. Transmission electron microscopy was employed to study internalization of bacteria by PMN. H. ducreyi and lipooligosaccharide preparations from these bacteria were able to induce conversion of complement factor C3 in normal human serum (NHS). Exposure of bacteria to NHS resulted in deposition of IgG, IgM and complement factors C1q and C3 on the surface of bacteria. H. ducreyi bacteria lost their viability when incubated with fresh but not inactivated normal serum at high concentrations, indicating that the bacteria are sensitive to the complement-dependent bactericidal activity of serum. There were some variations between different strains regarding their susceptibility to the bactericidal activity of NHS, but for eight strains tested, all of the bacteria exposed were not killed in medium containing up to 70% of fresh serum. Complement-mediated opsonophagocytic killing of H. ducreyi by PMN was more effective than complement-dependent bactericidal activity of fresh normal sera. Bacteria treated with heat inactivated immune sera, on the other hand, were as sensitive to the bactericidal effect of PMN as those treated with non-inactivated immune sera, indicating the role of antibodies in opsonophagocytosis. H. ducreyi bacteria were also killed by PMN in the absence of serum antibodies and complement. Using the chemiluminescence assay, H. ducreyi was shown to activate PMN in the absence of serum as well as after opsonization with complement and antibodies. Our results therefore indicate that both opsonic- and non-opsonic mechanisms are involved in the phagocytosis and the subsequent killing of H. ducreyi bacteria. Although both complement and antibodies enhance the ability of phagocytes to kill H. ducreyi, neither component is sufficient for effective killing of H. ducreyi.

Animals↗

Reference ranges for IgG, IgM and IgA in the serum of urban and rural Somalis.

In order to provide baseline data for an immuno-parasitological laboratory in Somalia, serum concentrations of IgG, IgM and IgA were determined in some key populations: healthy residents of Mogadishu (n = 157), inhabitants of the village of Daimo Samo (n = 276) and patients with malaria (n = 39) and visceral leishmaniasis (n = 26), both protozoan infections accompanied by hypergammaglobulinaemia and causing severe health problems in Somalia. Since the serum immunoglobulin concentrations in the Somali populations studied were not normally distributed, they were evaluated using medians and percentiles. Significantly higher values of IgG, IgM and IgA were demonstrated in healthy Mogadishu residents as compared to healthy Swedes. Daimo Samo villagers had significantly higher IgG and IgM values than healthy Mogadishu residents. Very high concentrations of IgG and IgM were demonstrated in sera from patients with visceral leishmaniasis. Somali patients with malaria also had marked hypergammaglobulinaemia, however, only in the IgG class. The high levels of IgG, IgM and IgA demonstrated in sera from Somalis, indicate the need for establishing local reference values and should be considered when introducing serological tests in tropical countries. Such methods are usually adopted to conditions in industrialized countries, where immunoglobulin contents of sera are lower.

Adolescent↗

Effect of cholera toxin on vaccine-induced immunity and infection in murine schistosomiasis mansoni.

Intradermal vaccination of mice with soluble adult worm antigen (SWAP) in combination with Mycobacterium bovis BCG (Swedish strain) induced significant protection against subsequent infection with Schistosoma mansoni cercariae. When cholera toxin (CT) was used as an adjuvant in combination with SWAP or fraction A, no significant protection was observed. However, intradermal vaccination in combination with CT triggered a strong anti-SWAP antibody response and induced a strong delayed-type hypersensitivity response to schistosome antigens (SWAP or fraction A), one significantly higher than that in the SWAP-BCG group. In addition, vaccinating mice intranasally with SWAP or cercarial antigen together with CT as adjuvant failed to induce any significant protection. Surprisingly, mice given CT alone intranasally revealed a significantly enhanced worm burden. These findings suggest that mucosal application of CT may modulate the host-parasite relationship in favor of parasite survival.

Animals↗

Schistosoma mansoni antibodies in tissue specimens demonstrated by a diffusion-in-gel ELISA technique.

A modification of the diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA) for analysis of antibodies in tissue fragments has been elaborated. In this technique, tissue specimens are placed on top of a thin gel layer covering a plastic surface coated with an antigen preparation. The gel thus serves as a medium through which diffusion of antibodies contained in tissue samples may occur. Specimens from skin, lung, liver, kidney, heart and skeletal muscle as well as blood serum and blood sampled onto filter paper were successfully used for analysis of the antibody response to two different antigens (soluble adult worm antigen and soluble egg antigen) during experimental infection of mice with the helminth parasite Schistosoma mansoni. It was concluded that skin and lung tissue reflected the serum antibody response more closely than the other tissues tested, although zone sizes were slightly smaller than those registered for corresponding serum samples. The DIG-ELISA reaction zone size was, as expected, shown to be dependent on the weight (size) of the tissue specimen. The variability of the modified technique was comparable to that found for analysis of serum by the conventional DIG-ELISA technique. It is concluded that the described technique may be used for serological analysis when blood samples cannot be easily obtained, e.g. at examination of animal carcasses or single organs.

Animals↗

Induction of anti-secretory factor in mice by the nonintestinal parasite Schistosoma mansoni.

Anti-secretory factor (ASF) was determined by the rat intestinal loop model in the pituitary gland and in the blood at various intervals after experimental infection of mice with Schistosoma mansoni. ASF could be detected in the pituitary gland by 6 hr after percutaneous infection with cercariae and in the blood at 24 hr after infection. A peak level was reached 3 days after infection and, after a decline, 2 more peaks were noted between 4 and 8 wk after infection. Characterization of ASF induced by S. mansoni by means of isoelectric focusing revealed 2 distinct peaks at approximately pH 4 and pH 5, respectively. Upon affinity chromatography on agarose, the activity dissociated in a gradient of methyl-alpha-D-glucoside at 1.0 M but not at 0.1 or 0.3 M concentrations.

Animals↗

Vaginal immunoglobulin A (IgA) levels in post-menopausal women: influence of oestriol therapy.

The concentration of secretory immunoglobulin A (IgA) in the vaginal fluid of 20 untreated post-menopausal women (aged 75.4 +/- 1.4 years) was compared with the levels in a group of 20 post-menopausal women (aged 73.2 +/- 1.5 years) treated with oral oestriol (E3) (2 mg/day) and a further group of 20 healthy, non-pregnant, fertile women (aged 28.2 +/- 1.8 years). Secretory IgA was determined using a paper disc modification of the single radial immunodiffusion technique. The vaginal concentration of IgA in the untreated women was 41.5 +/- 5.7 mg/l, which was higher than that recorded in those treated with E3 (20.8 +/- 5.7 mg/l, P less than 0.05) and in the fertile women (16.4 +/- 3.7 mg/l, P less than 0.01). Epithelial cells predominated in the wet smear preparations obtained from the women who received E3 and the fertile women, while a predominance of leucocytes was observed in the untreated women. Lactobacilli were found more frequently in the vaginal flora of the women in the E3 group (P less than 0.001) and the fertile women (P less than 0.001) than the untreated group. Faecal-type bacteria were seen more frequently in the vaginal flora of the untreated women than the E3 group (P less than 0.01) or the fertile women (P less than 0.001). The possible implications of the present findings with regard to the individual variation in the intensity of symptoms experienced by women suffering from the oestrogen deficiency syndrome are discussed.

Adult↗

Comparative antigen analysis of different life stages of Schistosoma mansoni by crossed immunoelectrophoresis.

Two-dimensional (crossed) immunoelectrophoresis was used for analysis of soluble antigen extracts obtained from the three developmental stages, cercariae, adult worms and eggs, of Schistosoma mansoni by using homologous hyperimmune sera produced in sheep. The antigenic relationships between the three stages as well as the possible relationship to the intermediate snail host were studied. Seven antigen components were shown to be shared between all three life stages of S. mansoni. Furthermore, one antigen was common to adult worm and snail, and one other antigen was shared between cercaria and snail. By using an intermediate gel containing lectin in the antigen-antibody system or by enzyme staining of the immune precipitates it was possible to identify schistosome antigens possessing lectin reactivity or enzyme activity. Characterization of enzyme activities revealed three individual precipitating antigens in adult worm of S. mansoni possessing esterase, leucyl-glycyl-glycine peptidase and phenylalanyl-leucine peptidase activities, respectively. One further precipitinogen with malate dehydrogenase activity was identified for all three life stages.

Animals↗