Increased bronchoalveolar IgG2/IgG1 ratio is a marker for human lung allograft rejection.

D. S. Wilkes, K. M. Heidler, M. Niemeier, G. R. Schwenk, P. N. Mathur, W. M. Breite, Oscar Cummings, J. C. Weissler

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Abstract

BACKGROUND: Lung allograft rejection (AR) is thought to involve T-helper-1 (Th-1) lymphocytes mediating both cellular immunity and alloantibody production. Th-1 lymphocytes produce gamma interferon (gamma IFN) and induce IgG2 production, suggesting that increased IgG2 production might occur during AR. The purpose of this study was to determine if locally altered bronchoalveolar IgG2/IgG1 ratios might correlate with AR. METHODS: Eighteen recipients of lung allografts underwent a total of 25 bronchoscopies for surveillance or at times of suspected infection or AR. Bronchoalveolar lavage (BAL), serum collection, and transbronchial biopsy (TB) were performed on all patients. gamma IFN, IgG1, IgG2 levels, and the ratio of IgG2/IgG1 were determined in serum and BAL and matched with TB histology. Five nonsmoking normal volunteers undergoing bronchoscopy, BAL, and serum collection served as controls. RESULTS: IgG2 was upregulated in allograft BAL during AR as determined by the ratio IgG2/IgG1 (2.91 +/- 0.79 SEM vs 0.62 +/- SEM, p < 0.019, IgG2/IgG1, AR BAL vs non-AR BAL, respectively). An IgG2/IgG1 > or = 1 in allograft BAL (95% confidence intervals 1.26 to 4.56) was 80% specific and 91% sensitive for the diagnosis of AR with a positive predictive value of 92%. A BAL IgG2/IgG1 < 1 (95% confidence interval 0.27 to 0.97) had a negative predictive value of 77%. After therapy in two patients the elevated IgG2/IgG1 ratio reversed to normal (ie, < 1) with histologic resolution of AR. CONCLUSIONS: Human lung AR is associated with a locally increased IgG2/IgG1 ratio suggesting locally upregulated Th-1 lymphocyte activity during lung AR.

Original languageEnglish
Pages (from-to)652-659
Number of pages8
JournalJournal of Investigative Medicine
Volume42
Issue number4
StatePublished - Dec 1994

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Allografts
Immunoglobulin G
Lung
Bronchoalveolar Lavage
Lymphocytes
Helper-Inducer T-Lymphocytes
Biopsy
Bronchoscopy
Interferon-gamma
Serum
Confidence Intervals
Isoantibodies
Scanning electron microscopy
Histology
Cellular Immunity
Healthy Volunteers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wilkes, D. S., Heidler, K. M., Niemeier, M., Schwenk, G. R., Mathur, P. N., Breite, W. M., ... Weissler, J. C. (1994). Increased bronchoalveolar IgG2/IgG1 ratio is a marker for human lung allograft rejection. Journal of Investigative Medicine, 42(4), 652-659.

Increased bronchoalveolar IgG2/IgG1 ratio is a marker for human lung allograft rejection. / Wilkes, D. S.; Heidler, K. M.; Niemeier, M.; Schwenk, G. R.; Mathur, P. N.; Breite, W. M.; Cummings, Oscar; Weissler, J. C.

In: Journal of Investigative Medicine, Vol. 42, No. 4, 12.1994, p. 652-659.

Research output: Contribution to journalArticle

Wilkes, DS, Heidler, KM, Niemeier, M, Schwenk, GR, Mathur, PN, Breite, WM, Cummings, O & Weissler, JC 1994, 'Increased bronchoalveolar IgG2/IgG1 ratio is a marker for human lung allograft rejection.', Journal of Investigative Medicine, vol. 42, no. 4, pp. 652-659.
Wilkes DS, Heidler KM, Niemeier M, Schwenk GR, Mathur PN, Breite WM et al. Increased bronchoalveolar IgG2/IgG1 ratio is a marker for human lung allograft rejection. Journal of Investigative Medicine. 1994 Dec;42(4):652-659.
Wilkes, D. S. ; Heidler, K. M. ; Niemeier, M. ; Schwenk, G. R. ; Mathur, P. N. ; Breite, W. M. ; Cummings, Oscar ; Weissler, J. C. / Increased bronchoalveolar IgG2/IgG1 ratio is a marker for human lung allograft rejection. In: Journal of Investigative Medicine. 1994 ; Vol. 42, No. 4. pp. 652-659.
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title = "Increased bronchoalveolar IgG2/IgG1 ratio is a marker for human lung allograft rejection.",
abstract = "BACKGROUND: Lung allograft rejection (AR) is thought to involve T-helper-1 (Th-1) lymphocytes mediating both cellular immunity and alloantibody production. Th-1 lymphocytes produce gamma interferon (gamma IFN) and induce IgG2 production, suggesting that increased IgG2 production might occur during AR. The purpose of this study was to determine if locally altered bronchoalveolar IgG2/IgG1 ratios might correlate with AR. METHODS: Eighteen recipients of lung allografts underwent a total of 25 bronchoscopies for surveillance or at times of suspected infection or AR. Bronchoalveolar lavage (BAL), serum collection, and transbronchial biopsy (TB) were performed on all patients. gamma IFN, IgG1, IgG2 levels, and the ratio of IgG2/IgG1 were determined in serum and BAL and matched with TB histology. Five nonsmoking normal volunteers undergoing bronchoscopy, BAL, and serum collection served as controls. RESULTS: IgG2 was upregulated in allograft BAL during AR as determined by the ratio IgG2/IgG1 (2.91 +/- 0.79 SEM vs 0.62 +/- SEM, p < 0.019, IgG2/IgG1, AR BAL vs non-AR BAL, respectively). An IgG2/IgG1 > or = 1 in allograft BAL (95{\%} confidence intervals 1.26 to 4.56) was 80{\%} specific and 91{\%} sensitive for the diagnosis of AR with a positive predictive value of 92{\%}. A BAL IgG2/IgG1 < 1 (95{\%} confidence interval 0.27 to 0.97) had a negative predictive value of 77{\%}. After therapy in two patients the elevated IgG2/IgG1 ratio reversed to normal (ie, < 1) with histologic resolution of AR. CONCLUSIONS: Human lung AR is associated with a locally increased IgG2/IgG1 ratio suggesting locally upregulated Th-1 lymphocyte activity during lung AR.",
author = "Wilkes, {D. S.} and Heidler, {K. M.} and M. Niemeier and Schwenk, {G. R.} and Mathur, {P. N.} and Breite, {W. M.} and Oscar Cummings and Weissler, {J. C.}",
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T1 - Increased bronchoalveolar IgG2/IgG1 ratio is a marker for human lung allograft rejection.

AU - Wilkes, D. S.

AU - Heidler, K. M.

AU - Niemeier, M.

AU - Schwenk, G. R.

AU - Mathur, P. N.

AU - Breite, W. M.

AU - Cummings, Oscar

AU - Weissler, J. C.

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N2 - BACKGROUND: Lung allograft rejection (AR) is thought to involve T-helper-1 (Th-1) lymphocytes mediating both cellular immunity and alloantibody production. Th-1 lymphocytes produce gamma interferon (gamma IFN) and induce IgG2 production, suggesting that increased IgG2 production might occur during AR. The purpose of this study was to determine if locally altered bronchoalveolar IgG2/IgG1 ratios might correlate with AR. METHODS: Eighteen recipients of lung allografts underwent a total of 25 bronchoscopies for surveillance or at times of suspected infection or AR. Bronchoalveolar lavage (BAL), serum collection, and transbronchial biopsy (TB) were performed on all patients. gamma IFN, IgG1, IgG2 levels, and the ratio of IgG2/IgG1 were determined in serum and BAL and matched with TB histology. Five nonsmoking normal volunteers undergoing bronchoscopy, BAL, and serum collection served as controls. RESULTS: IgG2 was upregulated in allograft BAL during AR as determined by the ratio IgG2/IgG1 (2.91 +/- 0.79 SEM vs 0.62 +/- SEM, p < 0.019, IgG2/IgG1, AR BAL vs non-AR BAL, respectively). An IgG2/IgG1 > or = 1 in allograft BAL (95% confidence intervals 1.26 to 4.56) was 80% specific and 91% sensitive for the diagnosis of AR with a positive predictive value of 92%. A BAL IgG2/IgG1 < 1 (95% confidence interval 0.27 to 0.97) had a negative predictive value of 77%. After therapy in two patients the elevated IgG2/IgG1 ratio reversed to normal (ie, < 1) with histologic resolution of AR. CONCLUSIONS: Human lung AR is associated with a locally increased IgG2/IgG1 ratio suggesting locally upregulated Th-1 lymphocyte activity during lung AR.

AB - BACKGROUND: Lung allograft rejection (AR) is thought to involve T-helper-1 (Th-1) lymphocytes mediating both cellular immunity and alloantibody production. Th-1 lymphocytes produce gamma interferon (gamma IFN) and induce IgG2 production, suggesting that increased IgG2 production might occur during AR. The purpose of this study was to determine if locally altered bronchoalveolar IgG2/IgG1 ratios might correlate with AR. METHODS: Eighteen recipients of lung allografts underwent a total of 25 bronchoscopies for surveillance or at times of suspected infection or AR. Bronchoalveolar lavage (BAL), serum collection, and transbronchial biopsy (TB) were performed on all patients. gamma IFN, IgG1, IgG2 levels, and the ratio of IgG2/IgG1 were determined in serum and BAL and matched with TB histology. Five nonsmoking normal volunteers undergoing bronchoscopy, BAL, and serum collection served as controls. RESULTS: IgG2 was upregulated in allograft BAL during AR as determined by the ratio IgG2/IgG1 (2.91 +/- 0.79 SEM vs 0.62 +/- SEM, p < 0.019, IgG2/IgG1, AR BAL vs non-AR BAL, respectively). An IgG2/IgG1 > or = 1 in allograft BAL (95% confidence intervals 1.26 to 4.56) was 80% specific and 91% sensitive for the diagnosis of AR with a positive predictive value of 92%. A BAL IgG2/IgG1 < 1 (95% confidence interval 0.27 to 0.97) had a negative predictive value of 77%. After therapy in two patients the elevated IgG2/IgG1 ratio reversed to normal (ie, < 1) with histologic resolution of AR. CONCLUSIONS: Human lung AR is associated with a locally increased IgG2/IgG1 ratio suggesting locally upregulated Th-1 lymphocyte activity during lung AR.

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