HLA and environmental interactions in sarcoidosis

Milton D. Rossman; B. Thompson; Margaret Frederick; Michael C. Iannuzzi; Benjamin A. Rybicki; Janardan P. Pandey; Lee S. Newman; Cecile Rose; E. Magira; D. Monos; Steven E. Weinberger; Patricia Finn; Erik Garpestad; Allison Moran; Henry Yeager; David L. Rabin; Susan Stein; Marcie Major; Mary Maliarik; John Popovich; David R. Moller; Carol J. Johns; Cynthia Rand; Joanne Steimel; Marc A. Judson; Susan D'Alessandro; Nancy Heister; Theresa Johnson; Daniel T. Lackland; Steven Sahn; Charlie Strange; Alvin S. Teirstein; Louis DePalo; Sheldon Brown; Marvin Lesser; Maria L. Padilla; Marilyn Marshall; Juli Barnard; Robert P. Baughman; Elyse E. Lower; Donna B. Winget; Geoffrey McLennan; Gary Hunninghake; Chuck Dayton; Linda Powers; Eddy A. Bresnitz; Ronald Daniele; Jackie Regovich; William Sexauer; Robert Musson; Joanne Deshler; Paul Sorlie; Margaret Wu; Reuben Cherniack; Genell L. Knatterud; Michael L. Terrin; Bruce W. Thompson; Kathleen Brown; Margaret Frederick; Frances LoPresti; Patricia Wilkins; Martha Canner; Judy Dotson; Steve Lindenfelser; Mark Cosentino

HLA and environmental interactions in sarcoidosis

Milton D. Rossman, B. Thompson, Margaret Frederick, Michael C. Iannuzzi, Benjamin A. Rybicki, Janardan P. Pandey, Lee S. Newman, Cecile Rose, E. Magira, D. Monos, Steven E. Weinberger, Patricia Finn, Erik Garpestad, Allison Moran, Henry Yeager, David L. Rabin, Susan Stein, Marcie Major, Mary Maliarik, John PopovichDavid R. Moller, Carol J. Johns, Cynthia Rand, Joanne Steimel, Marc A. Judson, Susan D'Alessandro, Nancy Heister, Theresa Johnson, Daniel T. Lackland, Steven Sahn, Charlie Strange, Alvin S. Teirstein, Louis DePalo, Sheldon Brown, Marvin Lesser, Maria L. Padilla, Marilyn Marshall, Juli Barnard, Robert P. Baughman, Elyse E. Lower, Donna B. Winget, Geoffrey McLennan, Gary Hunninghake, Chuck Dayton, Linda Powers, Eddy A. Bresnitz, Ronald Daniele, Jackie Regovich, William Sexauer, Robert Musson, Joanne Deshler, Paul Sorlie, Margaret Wu, Reuben Cherniack, Genell L. Knatterud, Michael L. Terrin, Bruce W. Thompson, Kathleen Brown, Margaret Frederick, Frances LoPresti, Patricia Wilkins, Martha Canner, Judy Dotson, Steve Lindenfelser, Mark Cosentino

Johns Hopkins Bayview Hospital

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

Abstract

Sarcoidosis is a systemic granulomatosis of unknown etiology despite being described over 100 years ago. While both genetic predisposition and environmental exposures have been proposed as playing a role in this disease, there have not been any systematic investigations of gene-environmental interaction in this disease. In the ACCESS dataset, detailed environmental histories and high resolution HLA class II typing were performed on 476 cases of newly diagnosed sarcoidosis and 476 matched controls from the patients' community. We evaluated gene-environmental interactions in exposures or HLA class II alleles that were present in > 5% of the population and had an odd ratio of > 1.0. Four exposures and four HLA Class II alleles met these criteria and were evaluated. Significant interaction was observed between HLA DRB1*1101 and insecticide exposure at work (p < 0.10) and suggestive interaction was observed between HLA DRB1*1101 and exposure to mold and musty odors and DRB1*1501 and insecticide exposure at work (P < 0.15). In addition, HLA DRB1*1101 and insecticide exposure at work was associated with extrapulmonary sarcoidosis, specifically cardiac sarcoidosis and hypercalcemia (p<0.05) and HLA DRB1*1101 and exposure to molds and musty odors was associated with pulmonary only sarcoidosis (P < 0.05). These studies suggest that sarcoidosis is due to an interaction of genetic predisposition and environmental exposure in at least some cases of sarcoidosis. Future studies in defined phenotypes of sarcoidosis may be necessary to define environmental and genetic associations with sarcoidosis.

Original language	English (US)
Pages (from-to)	125-132
Number of pages	8
Journal	Sarcoidosis Vasculitis and Diffuse Lung Diseases
Volume	25
Issue number	2
State	Published - 2008

Keywords

Autoimmunity
Genetics
Human
Lung
MHC

ASJC Scopus subject areas

Internal Medicine
Immunology and Allergy
Pulmonary and Respiratory Medicine

Cite this

Rossman, M. D., Thompson, B., Frederick, M., Iannuzzi, M. C., Rybicki, B. A., Pandey, J. P., Newman, L. S., Rose, C., Magira, E., Monos, D., Weinberger, S. E., Finn, P., Garpestad, E., Moran, A., Yeager, H., Rabin, D. L., Stein, S., Major, M., Maliarik, M., ... Cosentino, M. (2008). HLA and environmental interactions in sarcoidosis. Sarcoidosis Vasculitis and Diffuse Lung Diseases, 25(2), 125-132.

Rossman, MD, Thompson, B, Frederick, M, Iannuzzi, MC, Rybicki, BA, Pandey, JP, Newman, LS, Rose, C, Magira, E, Monos, D, Weinberger, SE, Finn, P, Garpestad, E, Moran, A, Yeager, H, Rabin, DL, Stein, S, Major, M, Maliarik, M, Popovich, J, Moller, DR, Johns, CJ, Rand, C, Steimel, J, Judson, MA, D'Alessandro, S, Heister, N, Johnson, T, Lackland, DT, Sahn, S, Strange, C, Teirstein, AS, DePalo, L, Brown, S, Lesser, M, Padilla, ML, Marshall, M, Barnard, J, Baughman, RP, Lower, EE, Winget, DB, McLennan, G, Hunninghake, G, Dayton, C, Powers, L, Bresnitz, EA, Daniele, R, Regovich, J, Sexauer, W, Musson, R, Deshler, J, Sorlie, P, Wu, M, Cherniack, R, Knatterud, GL, Terrin, ML, Thompson, BW, Brown, K, Frederick, M, LoPresti, F, Wilkins, P, Canner, M, Dotson, J, Lindenfelser, S & Cosentino, M 2008, 'HLA and environmental interactions in sarcoidosis', Sarcoidosis Vasculitis and Diffuse Lung Diseases, vol. 25, no. 2, pp. 125-132.

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title = "HLA and environmental interactions in sarcoidosis",

abstract = "Sarcoidosis is a systemic granulomatosis of unknown etiology despite being described over 100 years ago. While both genetic predisposition and environmental exposures have been proposed as playing a role in this disease, there have not been any systematic investigations of gene-environmental interaction in this disease. In the ACCESS dataset, detailed environmental histories and high resolution HLA class II typing were performed on 476 cases of newly diagnosed sarcoidosis and 476 matched controls from the patients' community. We evaluated gene-environmental interactions in exposures or HLA class II alleles that were present in > 5% of the population and had an odd ratio of > 1.0. Four exposures and four HLA Class II alleles met these criteria and were evaluated. Significant interaction was observed between HLA DRB1*1101 and insecticide exposure at work (p < 0.10) and suggestive interaction was observed between HLA DRB1*1101 and exposure to mold and musty odors and DRB1*1501 and insecticide exposure at work (P < 0.15). In addition, HLA DRB1*1101 and insecticide exposure at work was associated with extrapulmonary sarcoidosis, specifically cardiac sarcoidosis and hypercalcemia (p<0.05) and HLA DRB1*1101 and exposure to molds and musty odors was associated with pulmonary only sarcoidosis (P < 0.05). These studies suggest that sarcoidosis is due to an interaction of genetic predisposition and environmental exposure in at least some cases of sarcoidosis. Future studies in defined phenotypes of sarcoidosis may be necessary to define environmental and genetic associations with sarcoidosis.",

keywords = "Autoimmunity, Genetics, Human, Lung, MHC",

author = "Rossman, {Milton D.} and B. Thompson and Margaret Frederick and Iannuzzi, {Michael C.} and Rybicki, {Benjamin A.} and Pandey, {Janardan P.} and Newman, {Lee S.} and Cecile Rose and E. Magira and D. Monos and Weinberger, {Steven E.} and Patricia Finn and Erik Garpestad and Allison Moran and Henry Yeager and Rabin, {David L.} and Susan Stein and Marcie Major and Mary Maliarik and John Popovich and Moller, {David R.} and Johns, {Carol J.} and Cynthia Rand and Joanne Steimel and Judson, {Marc A.} and Susan D'Alessandro and Nancy Heister and Theresa Johnson and Lackland, {Daniel T.} and Steven Sahn and Charlie Strange and Teirstein, {Alvin S.} and Louis DePalo and Sheldon Brown and Marvin Lesser and Padilla, {Maria L.} and Marilyn Marshall and Juli Barnard and Baughman, {Robert P.} and Lower, {Elyse E.} and Winget, {Donna B.} and Geoffrey McLennan and Gary Hunninghake and Chuck Dayton and Linda Powers and Bresnitz, {Eddy A.} and Ronald Daniele and Jackie Regovich and William Sexauer and Robert Musson and Joanne Deshler and Paul Sorlie and Margaret Wu and Reuben Cherniack and Knatterud, {Genell L.} and Terrin, {Michael L.} and Thompson, {Bruce W.} and Kathleen Brown and Margaret Frederick and Frances LoPresti and Patricia Wilkins and Martha Canner and Judy Dotson and Steve Lindenfelser and Mark Cosentino",

year = "2008",

language = "English (US)",

volume = "25",

pages = "125--132",

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T1 - HLA and environmental interactions in sarcoidosis

AU - Rossman, Milton D.

AU - Thompson, B.

AU - Frederick, Margaret

AU - Iannuzzi, Michael C.

AU - Rybicki, Benjamin A.

AU - Pandey, Janardan P.

AU - Newman, Lee S.

AU - Rose, Cecile

AU - Magira, E.

AU - Monos, D.

AU - Weinberger, Steven E.

AU - Finn, Patricia

AU - Garpestad, Erik

AU - Moran, Allison

AU - Yeager, Henry

AU - Rabin, David L.

AU - Stein, Susan

AU - Major, Marcie

AU - Maliarik, Mary

AU - Popovich, John

AU - Moller, David R.

AU - Johns, Carol J.

AU - Rand, Cynthia

AU - Steimel, Joanne

AU - Judson, Marc A.

AU - D'Alessandro, Susan

AU - Heister, Nancy

AU - Johnson, Theresa

AU - Lackland, Daniel T.

AU - Sahn, Steven

AU - Strange, Charlie

AU - Teirstein, Alvin S.

AU - DePalo, Louis

AU - Brown, Sheldon

AU - Lesser, Marvin

AU - Padilla, Maria L.

AU - Marshall, Marilyn

AU - Barnard, Juli

AU - Baughman, Robert P.

AU - Lower, Elyse E.

AU - Winget, Donna B.

AU - McLennan, Geoffrey

AU - Hunninghake, Gary

AU - Dayton, Chuck

AU - Powers, Linda

AU - Bresnitz, Eddy A.

AU - Daniele, Ronald

AU - Regovich, Jackie

AU - Sexauer, William

AU - Musson, Robert

AU - Deshler, Joanne

AU - Sorlie, Paul

AU - Wu, Margaret

AU - Cherniack, Reuben

AU - Knatterud, Genell L.

AU - Terrin, Michael L.

AU - Thompson, Bruce W.

AU - Brown, Kathleen

AU - Frederick, Margaret

AU - LoPresti, Frances

AU - Wilkins, Patricia

AU - Canner, Martha

AU - Dotson, Judy

AU - Lindenfelser, Steve

AU - Cosentino, Mark

PY - 2008

Y1 - 2008

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KW - Autoimmunity

KW - Genetics

KW - Human

KW - Lung

KW - MHC

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JO - Sarcoidosis Vasculitis and Diffuse Lung Diseases

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ER -

HLA and environmental interactions in sarcoidosis

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Keywords

ASJC Scopus subject areas

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