Pertussis toxin enhanced IgG1 and IgE responses to primary tetanus immunization are mediated by interleukin-4 and persist during secondary responses to tetanus alone

Samore, Matthew H.; Siber, George R.

doi:10.1016/0264-410x(95)00201-b

Cited by 31 publications

(15 citation statements)

References 35 publications

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“…The mechanism of suppression of antibody responses by PT is unclear. Several reports in the literature demonstrate that PT has adjuvant activities, including increasing antibody responses (36,37,47). However, this result occurred in the absence of the bacteria or other B. pertussis antigens and may have involved an artificially high concentration of PT.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Serum Antibody Responses by Pertussis Toxin after Respiratory Tract Colonization byBordetella pertussisand Identification of an Immunodominant Lipoprotein

Carbonetti¹,

Артамонова²,

Andreasen³

et al. 2004

Infect Immun

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Pertussis toxin (PT), a virulence factor secreted by Bordetella pertussis, contributes to respiratory tract infection and disease caused by this pathogen. By comparing a wild-type (WT) B. pertussis strain to a mutant strain with an in-frame deletion of the ptx genes encoding PT (⌬PT), we recently found that the lack of PT confers a significant defect in respiratory tract colonization in mice after intranasal inoculation. In this study, we analyzed serum antibody responses in mice infected with the WT or ⌬PT strain and found that infection with the ⌬PT strain elicited greater responses to several B. pertussis antigens than did infection with the WT, despite the lower colonization level achieved by the ⌬PT strain. The same enhanced antibody response was observed after infection with a strain expressing an enzymatically inactive PT; but this response was not observed after infection with B. pertussis mutant strains lacking filamentous hemagglutinin or adenylate cyclase toxin, nor when purified PT was administered with the ⌬PT inoculum, indicating a specific role for PT activity in this immunosuppressive effect. In particular, there were consistent strong serum antibody responses to one or more low-molecular-weight antigens after infection with the ⌬PT strain. These antigens were Bvg independent, membrane localized, and also expressed by the closely related pathogens Bordetella parapertussis and Bordetella bronchiseptica. Two-dimensional gel electrophoresis and mass spectrometry were used to identify one of the immunodominant low-molecular-weight antigens as a protein with significant sequence homology to peptidoglycan-associated lipoprotein in several other gram-negative bacterial species. However, a serum antibody response to this protein alone did not protect mice against respiratory tract infection by B. pertussis.Pertussis toxin (PT) is an important virulence factor produced exclusively by Bordetella pertussis, a gram-negative bacterial pathogen that colonizes the human respiratory tract and causes a disease known as whooping cough or pertussis. PT is a member of the AB 5 structural class of bacterial toxins (41, 43), consisting of an enzymatically active A subunit (S1) that ADP-ribosylates the alpha subunit of the Gi family of heterotrimeric G proteins in mammalian cells (17, 30) and a pentameric B oligomer that binds unidentified glycoconjugate receptors on cells (5, 48). PT activity has a wide range of effects on signaling pathways and normal function in mammalian cells (35,49). The administration of purified PT to experimental animals can reproduce almost all of the systemic symptoms associated with human pertussis disease, such as histamine sensitivity, lymphocytosis, and insulinemia (29, 31, 32), but its role in respiratory tract colonization and disease is uncertain. Several studies of mice intranasally infected with bacteria have shown that PT plays a role in the overall respiratory tract infection by B. pertussis (2,10,45,46). Recently, it was found that PT is a significant colonization factor for resp...

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Section: Discussionmentioning

confidence: 99%

Suppression of Serum Antibody Responses by Pertussis Toxin after Respiratory Tract Colonization byBordetella pertussisand Identification of an Immunodominant Lipoprotein

Carbonetti¹,

Артамонова²,

Andreasen³

et al. 2004

Infect Immun

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“…Two other cross-sectional surveys, one conducted in London and one using US Third National Health and Nutrition Examination Survey data, also reported an association (163,164). In addition, some laboratory results have supported increased levels of IgE in subjects exposed to diphtheria, pertussis, and tetanus antigens (101,165,166). The Avon Longitudinal Study of Parents and Children (ALSPAC) cohort found no increased risk associated with pertussis vaccination for wheezing illnesses in young English children (84).…”

Section: Environmental and Lifestyle Factorsmentioning

confidence: 96%

Environmental Epidemiology of Pediatric Asthma and Allergy

Johnson

Ownby²,

Zoratti

et al. 2002

Epidemiologic Reviews

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“…Our patient received a toxoid rather than a toxin (not designed to have any particular affinity for melanoma cells) and so it is unlikely that direct cellular toxicity from the diphtheria component is a trigger for the observed remission. Pertussis toxin has been shown to possess adjuvant properties that are able to enhance both the humoral response and the Th1 and Th2 responses to antigens [19][20][21][22] .…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Regression of Metastatic Melanoma after Inoculation with Tetanus–Diphtheria–Pertussis Vaccine

Tran

Burt²,

Eapen

et al. 2013

Current Oncology

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After 3 months, a right inguinal lymph node dissection revealed involvement in 1 of 6 lymph nodes. Clinical examination and computed tomography imaging showed no evidence of distant metastasis. The patient was considered to have T2bN1aM0 stage iiib disease.One month later, the patient started a 4-week induction course of adjuvant high-dose interferon alfa at a daily dose of 36×10 6 U intravenously 5 days per week, followed by an 11-month course of 18×10 6 U interferon alfa 3 times weekly subcutaneously for maintenance. He tolerated this regimen well, with some symptoms of muscle pain, diarrhea, fever, and occasional headaches in addition to a slight elevation of liver enzymes.Eleven months into therapy, the patient developed multiple (approximately 15) in-transit metastases in the upper right thigh. These erythematous lesions ranged in size from 1 mm to 10 mm. Two other similar subcutaneous nodules were also seen on the upper lateral aspect of the right thigh (Figure 1). The patient underwent palliative radiotherapy of 40 Gy in 10 fractions to each nodule and 30 Gy in 10 fractions to the intervening skin, with good response. Followup imaging showed no other recurrence. The patient completed his 1-year course of interferon.Six months after the course of interferon, the patient developed a tender 5-mm nodule above the left nipple, a 5-mm axillary nodule, and a small nodule under the chin and on the central back. The chest lesion was excised and proved to be melanoma. A punch biopsy of the left axillary nodule revealed a malignant non-melanin tumour. Immunohistochemistry for melanoma was positive for S100, mart-1, and tyrosinase, and negative for HMB45, suggesting metastatic disease 1 . Immunohistochemistry of the primary lesion was not available. In addition, imaging showed new right-middle-lobe lung nodules measuring up to 3.5 mm in diameter, and an enlarged 15×13-mm right external iliac lymph node. Investigations were initiated for enrollment in a trial for what was now stage iv disease. ABSTRACTSpontaneous regression of metastatic melanoma is an exceedingly rare event, with only 76 well-documented cases in the literature since 1866. Here, we present the case of a patient who developed metastatic melanoma despite interferon therapy and who then achieved spontaneous regression shortly after a reaction to tetanus-diphtheria-pertussis vaccination. A common theme among these cases is the development of febrile illness before remission of the malignant disease. A brief overview of proposed mechanisms for these miraculous recoveries is presented, including a highlight on the potential role of the herv-k-mel viral marker, a nona-or decapeptide that appears in most melanomas, with homologies to peptides in pathogenic microorganisms.

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Pertussis toxin enhanced IgG1 and IgE responses to primary tetanus immunization are mediated by interleukin-4 and persist during secondary responses to tetanus alone

Cited by 31 publications

References 35 publications

Suppression of Serum Antibody Responses by Pertussis Toxin after Respiratory Tract Colonization byBordetella pertussisand Identification of an Immunodominant Lipoprotein

Suppression of Serum Antibody Responses by Pertussis Toxin after Respiratory Tract Colonization byBordetella pertussisand Identification of an Immunodominant Lipoprotein

Environmental Epidemiology of Pediatric Asthma and Allergy

Spontaneous Regression of Metastatic Melanoma after Inoculation with Tetanus–Diphtheria–Pertussis Vaccine

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