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Humoral immune response in infants after Bacillus Calmette-Guérin (BCG) vaccination
TubercleandLung Disease(1996) 77, 98-100 © 1996 Pearson ProfessionalLtd
Correspondence
and non-vaccinated children in the same geographical region by assay techniques able to distinguish between the effects of BCG and those of other mycobacteria.
Humoral immune response in infants after Bacillus Calmette-Gu~rin (BCG) vaccination In their article in the June 1995 (volume 76, issue 3) edition of Tubercle and Lung Disease Beyazova et al state that anti-PPD antibodies in the IgG and IgM classes rise progressively in BCG-vaccinated infants. 1 This may well be the case but, as antibody levels were not assayed in a control group of non-vaccinated infants, the contribution of the vaccination to the observed rise cannot be determined from the data presented. The principal question raised by this study is whether the assayed antibodies are induced by, and specific to, BCG or whether they are the result of contact with mycobacteria in the environment. The use of PPD as antigen in the assay could certainly detect antibody to the latter organisms as many of its epitopes are common to all mycobactefial species.2 The authors state that IgM levels 2 and 4 months after vaccination were higher in the group of infants vaccinated later and speculate that this is due to insufficiency of immunoglobulin synthesis in early infancy. An equally plausible explanation is that infants vaccinated later had higher levels of IgM antibody due to a longer period of exposure to environmental mycobacteria. In the case of IgG, the pre-vaccination antibodies are almost certainly maternally derived, explaining the lower levels 2 months post-vaccination as such antibodies decay over the first 3 months of life, after which they are replaced by the child's own IgG. A similar decrease in IgM does not occur as antibodies in this class do not cross the placenta and are therefore not maternally derived. Neonatal BCG vaccination could elicit antimycobacterial antibodies per se, it could prime the vaccinated infant to mount a more intense humoral immune response to environmental mycobacteria or, conversely, it could down-regulate such a response as there is evidence of an inverse relationship between humoral and cell-mediated immune responses to antigens of BCG in persons sensitized by mycobacteria. 4 (This probably reflects the balance between Thl and Th2 helper T cells.) All could be of relevance to host defence as there is some evidence that antimycobacterial antibody may limit dissemination of disease in primary tuberculosis, 3 and there is little doubt that immune responses to environmental mycobacteria early in life determine the nature of responses to infection by Mycobacterium tuberculosis later in life. 5'6 In order to shed light on this topic, it will be necessary to compare and contrast antibody levels in vaccinated
John M Grange
National Heart and Lung Institute Royal Brompton Hospital London SW3 6NP, UK John L Stanford
University College London Medical School London WIP 7LD, UK
References 1. Beyazova U, Rota S, CevherogluT, Karsligil T. Humoral immune response in infants after BCG vaccination. Tubercle Lung Dis 1995; 76: 248-253. 2. Stanford J L. Immunologicallyimportant constituents of mycobacteria: antigens. In: Ratledge C, Stanford J L eds. The Biology of the Mycobacteria, Vol 2. London: AcademicPress, 1983: pp 85-127. 3. Costello S M deL, Kumar A, Narayan Vet al. Does antibody to mycobacterial antigens, including lipoarabinomannan, limit dissemination in childhood tuberculosis? Trans Roy Soc Trop Med Hyg 1992; 86: 686-92. 4. Pitchappan R M, Brahmajothi V, Rajaram K, SubramanyamP T, Balakrishnan K, Muthuveeralakshmi R. Spectrum of immune reactivity to mycobacterial (BCG) antigens in healthy hospital contacts in South India. Tubercle 1991; 72: 133-139. 5. Stanford J L, Shield M J, Rook G A W. Hypothesis:How environmental mycobacteriamay predetermine the protective efficacy of BCG. Tubercle 1981; 62: 55-62. 6. Bretscher P A. A strategy to improve the efficacy of vaccination against tuberculosis and leprosy. Immunol Today 1992; 13: 342-345.
Unusual multiple tuberculomas of the bilateral lung A 42-year-old woman was admitted to our institution with abnormal lung shadow. She was asymptomatic, and laboratory examinations, including tumor marker, showed no abnormality. Chest X-ray showed ten rounded opacities varying from 5 m m to 1.5 cm in diameter on the bilateral lung field. The opacities were well-defined and homogeneous without calcification, cavities or satellite shadows revealed by chest computerized tomography (CT) scan, suggesting pulmonary metastases. Whole body examination by CT scan, echogram, barium enema, and upper gastro-intestinal scintigram showed no abnormality. Sputum smear was negative. Because of concern that the opacities might present pulmonary metastases, the patient underwent thoracoscopic partial resection of the right lung. Macroscopically, the nodules had fleshy solid tissue 98
Correspondence
and non-vaccinated children in the same geographical region by assay techniques able to distinguish between the effects of BCG and those of other mycobacteria.
Humoral immune response in infants after Bacillus Calmette-Gu~rin (BCG) vaccination In their article in the June 1995 (volume 76, issue 3) edition of Tubercle and Lung Disease Beyazova et al state that anti-PPD antibodies in the IgG and IgM classes rise progressively in BCG-vaccinated infants. 1 This may well be the case but, as antibody levels were not assayed in a control group of non-vaccinated infants, the contribution of the vaccination to the observed rise cannot be determined from the data presented. The principal question raised by this study is whether the assayed antibodies are induced by, and specific to, BCG or whether they are the result of contact with mycobacteria in the environment. The use of PPD as antigen in the assay could certainly detect antibody to the latter organisms as many of its epitopes are common to all mycobactefial species.2 The authors state that IgM levels 2 and 4 months after vaccination were higher in the group of infants vaccinated later and speculate that this is due to insufficiency of immunoglobulin synthesis in early infancy. An equally plausible explanation is that infants vaccinated later had higher levels of IgM antibody due to a longer period of exposure to environmental mycobacteria. In the case of IgG, the pre-vaccination antibodies are almost certainly maternally derived, explaining the lower levels 2 months post-vaccination as such antibodies decay over the first 3 months of life, after which they are replaced by the child's own IgG. A similar decrease in IgM does not occur as antibodies in this class do not cross the placenta and are therefore not maternally derived. Neonatal BCG vaccination could elicit antimycobacterial antibodies per se, it could prime the vaccinated infant to mount a more intense humoral immune response to environmental mycobacteria or, conversely, it could down-regulate such a response as there is evidence of an inverse relationship between humoral and cell-mediated immune responses to antigens of BCG in persons sensitized by mycobacteria. 4 (This probably reflects the balance between Thl and Th2 helper T cells.) All could be of relevance to host defence as there is some evidence that antimycobacterial antibody may limit dissemination of disease in primary tuberculosis, 3 and there is little doubt that immune responses to environmental mycobacteria early in life determine the nature of responses to infection by Mycobacterium tuberculosis later in life. 5'6 In order to shed light on this topic, it will be necessary to compare and contrast antibody levels in vaccinated
John M Grange
National Heart and Lung Institute Royal Brompton Hospital London SW3 6NP, UK John L Stanford
University College London Medical School London WIP 7LD, UK
References 1. Beyazova U, Rota S, CevherogluT, Karsligil T. Humoral immune response in infants after BCG vaccination. Tubercle Lung Dis 1995; 76: 248-253. 2. Stanford J L. Immunologicallyimportant constituents of mycobacteria: antigens. In: Ratledge C, Stanford J L eds. The Biology of the Mycobacteria, Vol 2. London: AcademicPress, 1983: pp 85-127. 3. Costello S M deL, Kumar A, Narayan Vet al. Does antibody to mycobacterial antigens, including lipoarabinomannan, limit dissemination in childhood tuberculosis? Trans Roy Soc Trop Med Hyg 1992; 86: 686-92. 4. Pitchappan R M, Brahmajothi V, Rajaram K, SubramanyamP T, Balakrishnan K, Muthuveeralakshmi R. Spectrum of immune reactivity to mycobacterial (BCG) antigens in healthy hospital contacts in South India. Tubercle 1991; 72: 133-139. 5. Stanford J L, Shield M J, Rook G A W. Hypothesis:How environmental mycobacteriamay predetermine the protective efficacy of BCG. Tubercle 1981; 62: 55-62. 6. Bretscher P A. A strategy to improve the efficacy of vaccination against tuberculosis and leprosy. Immunol Today 1992; 13: 342-345.
Unusual multiple tuberculomas of the bilateral lung A 42-year-old woman was admitted to our institution with abnormal lung shadow. She was asymptomatic, and laboratory examinations, including tumor marker, showed no abnormality. Chest X-ray showed ten rounded opacities varying from 5 m m to 1.5 cm in diameter on the bilateral lung field. The opacities were well-defined and homogeneous without calcification, cavities or satellite shadows revealed by chest computerized tomography (CT) scan, suggesting pulmonary metastases. Whole body examination by CT scan, echogram, barium enema, and upper gastro-intestinal scintigram showed no abnormality. Sputum smear was negative. Because of concern that the opacities might present pulmonary metastases, the patient underwent thoracoscopic partial resection of the right lung. Macroscopically, the nodules had fleshy solid tissue 98