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Mucosal and systemic immune responses in patients with diarrhea due to CS6-expressing enterotoxigenic Escherichia coli - PubMed

Mucosal and systemic immune responses in patients with diarrhea due to CS6-expressing enterotoxigenic Escherichia coli

Firdausi Qadri et al. Infect Immun. 2007 May.

Abstract

Colonization factor CS6 expressed by enterotoxigenic Escherichia coli (ETEC) is a nonfimbrial polymeric protein. A substantial proportion of ETEC strains isolated from patients in endemic settings and in people who travel to regions where ETEC is endemic are ETEC strains expressing CS6, either alone or in combination with fimbrial colonization factor CS5 or CS4. However, relatively little is known about the natural immune responses elicited against CS6 expressed by ETEC strains causing disease. We studied patients who were hospitalized with diarrhea (n = 46) caused by CS6-expressing ETEC (ETEC expressing CS6 or CS5 plus CS6) and had a disease spectrum ranging from severe dehydration (27%) to moderate or mild dehydration (73%). Using recombinant CS6 antigen, we found that more than 90% of the patients had mucosal immune responses to CS6 expressed as immunoglobulin (IgA) antibody-secreting cells (ASC) or antibody in lymphocyte supernatant (ALS) and that about 57% responded with CS6-specific IgA antibodies in feces. More than 80% of the patients showed IgA seroconversion to CS6. Significant increases in the levels of anti-CS6 antibodies of the IgG isotype were also observed in assays for ASC (75%), ALS (100%), and serum (70%). These studies demonstrated that patients hospitalized with the noninvasive enteric pathogen CS6-expressing ETEC responded with both mucosal and systemic antibodies against CS6. Studies are needed to determine if the anti-CS6 responses protect against reinfection and if protective levels of CS6 immunity are induced by vaccination.

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Figures

FIG. 1.
FIG. 1.

(a) IgA and IgG ASC responses to CS6 antigen in adult patients infected with CS6-expressing ETEC. The responses to CS6 after the onset of diarrhea at the acute stage (day 2 [D2]) and at the early convalescence stage (day 7 [D7]) are shown, as are the responses in adult healthy controls (HC). The response frequency indicates the number of patients responding with ≥10 ASC/106 PBMC in all the patients studied. The bars indicate geometric means, and the error bars indicate standard errors of the means. Asterisks indicate statistically significant differences (one asterisk, P < 0.05 to 0.01; two asterisks, P < 0.01 to 0.001; three asterisks, P < 0.001) at day 7 compared to the responses at day 2. Phi indicates that there was a significant difference between patients at day 7 and healthy controls (P < 0.001). MNC, peripheral blood mononuclear cells. (b) IgA and IgG antibody responses to CS6 antigen in ALS specimens from adult patients with CS6-expressing ETEC. The responses to CS6 after the onset of acute-stage diarrhea (day 2 [D2]) and at the early convalescence stage (day 7 [D7]) are shown, as are the responses in adult healthy controls (HC). The response frequency indicates the number of patients responding with titers of ≥2/107 PBMC for all patients studied. The bars indicate geometric mean titers (GMT), and the error bars indicate standard errors of the means. Asterisks indicate statistically significant differences (one asterisk, P < 0.05 to 0.01; two asterisks, P < 0.01 to 0.001; three asterisks, P < 0.001) at day 7 compared to the responses at day 2. Phi indicates that there was a significant difference between patients at day 7 and healthy controls (P < 0.001). +ve, positive.

FIG. 2.
FIG. 2.

IgA antibody responses to CS6 in sera from patients with diarrhea caused by ETEC expressing CS6 or ETEC expressing CS5 plus CS6. The responses to CS6 after the onset of diarrhea at the acute stage (day 2 [D2]) and at the early (day 7 [D7]) and late (day 21 [D2]1) convalescence stages in the patients are shown. The bars indicate geometric mean titers (GMT), and the error bars indicate standard errors of the means. The response frequency indicates the number of patients responding with ≥2-fold increases in antibody titers for all patients studied. Asterisks indicate that there were statistically significant differences between the responses in the acute stage of disease and the responses in the early or late convalescent stage of disease (one asterisk, P < 0.05; two asterisks, P = 0.001; three asterisks, P < 0.001).

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