publication . Other literature type . Article . 2003

Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood

Lynda Bennett; A Karolina Palucka; Edsel Arce; Victoria Cantrell; Josef Borvak; Jacques Banchereau; Virginia Pascual;
  • Published: 17 Mar 2003
  • Publisher: Rockefeller University Press
Abstract
<jats:p>Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease characterized by flares of high morbidity. Using oligonucleotide microarrays, we now show that active SLE can be distinguished by a remarkably homogeneous gene expression pattern with overexpression of granulopoiesis-related and interferon (IFN)-induced genes. Using the most stringent statistical analysis (Bonferroni correction), 15 genes were found highly up-regulated in SLE patients, 14 of which are targets of IFN and one, defensin DEFA-3, a major product of immature granulocytes. A more liberal correction (Benjamini and Hochberg correction) yielded 18 additional genes, 12 of...
Subjects
Medical Subject Headings: skin and connective tissue diseases
free text keywords: Article, microarray, immature granulocytes, glucocorticoid, leukocytes, autoimmunity, Immunology, Immunology and Allergy, Autoimmune disease, medicine.disease, medicine, Lupus erythematosus, Defensin, Granulopoiesis, Molecular biology, Interferon, medicine.drug, Gene expression profiling, business.industry, business, Cytokine, medicine.medical_treatment, Leukopoiesis
Funded by
NIH| ECTOPIC GERMINAL CENTER REACTION IN SYSTEMIC LUPUS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01AR046589-01
  • Funding stream: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
,
NIH| BAA-CLIN. TRIALS &CLIN. MARKERS FOR IMMUNILOGIC DISEASE-266005412
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: N01AI005412-005
  • Funding stream: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
44 references, page 1 of 3

1 Kammer, G.M., and G.C. Tsokos. 1999. Lupus: Molecular and Cellular Pathogenesis. Humana Press, Totowa, NJ. 728 pp.

2 Lahita, R.G. 1999. Systemic Lupus Erythematosus. Academic Press. 3rd edition. San Diego, CA. 1051 pp.

3 Wakeland, E.K., K. Liu, R.R. Graham, and T.W. Behrens. 2001. Delineating the genetic basis of systemic lupus erythematosus. Immunity. 15:397–408. 11567630 [PubMed]

4 Shlomchik, M.J., J.E. Craft, and M.J. Mamula. 2001. From T to B and back again: positive feedback in systemic autoimmune disease. Nat. Rev. Immunol. 1:147–153. 11905822 [PubMed]

5 Davidson, A., and B. Diamond. 2001. Autoimmune diseases. N. Engl. J. Med. 345:340–350. 11484692 [PubMed]

6 Freed, J.H., A. Marrs, J. VanderWall, P.L. Cohen, and R.A. Eisenberg. 2000. MHC class II-bound self peptides from autoimmune MRL/lpr mice reveal potential T cell epitopes for autoantibody production in murine systemic lupus erythematosus. J. Immunol. 164:4697–4705. 10779775 [PubMed]

7 Kaliyaperumal, A., M.A. Michaels, and S.K. Datta. 2002. Naturally processed chromatin peptides reveal a major autoepitope that primes pathogenic T and B cells of lupus. J. Immunol. 168:2530–2537. 11859148 [PubMed]

8 Lipsky, P.E. 2001. Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat. Immunol. 2:764–766. 11526379 [PubMed]

9 Arce, E., D.G. Jackson, M.A. Gill, L.B. Bennett, J. Banchereau, and V. Pascual. 2001. Increased frequency of pre-germinal center b cells and plasma cell precursors in the blood of children with systemic lupus erythematosus. J. Immunol. 167:2361–2369. 11490026 [PubMed]

10 Rubin, R.L., F.L. Tang, E.K. Chan, K.M. Pollard, G. Tsay, and E.M. Tan. 1986. IgG subclasses of autoantibodies in systemic lupus erythematosus, Sjogren's syndrome, and drug-induced autoimmunity. J. Immunol. 137:2528–2534. 3760566 [PubMed]

11 Casciola-Rosen, L.A., G. Anhalt, and A. Rosen. 1994. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J. Exp. Med. 179:1317–1330. 7511686 [OpenAIRE] [PubMed]

12 Amoura, Z., J.C. Piette, H. Chabre, P. Cacoub, T. Papo, B. Wechsler, J.F. Bach, and S. Koutouzov. 1997. Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus: correlation with serum antinucleosome antibody titers and absence of clear association with disease activity. Arthritis Rheum. 40:2217–2225. 9416860 [PubMed]

13 Banchereau, J., F. Briere, C. Caux, J. Davoust, S. Lebecque, Y. Liu, B. Pulendran, and K. Palucka. 2000. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18:767–811. 10837075 [PubMed]

14 Steinman, R.M., S. Turley, I. Mellman, and K. Inaba. 2000. The induction of tolerance by dendritic cells that have captured apoptotic cells. J. Exp. Med. 191:411–416. 10662786 [OpenAIRE] [PubMed]

15 Blanco, P., A.K. Palucka, M. Gill, V. Pascual, and J. Banchereau. 2001. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science. 294:1540–1543. 11711679 [OpenAIRE] [PubMed]

44 references, page 1 of 3
Abstract
<jats:p>Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease characterized by flares of high morbidity. Using oligonucleotide microarrays, we now show that active SLE can be distinguished by a remarkably homogeneous gene expression pattern with overexpression of granulopoiesis-related and interferon (IFN)-induced genes. Using the most stringent statistical analysis (Bonferroni correction), 15 genes were found highly up-regulated in SLE patients, 14 of which are targets of IFN and one, defensin DEFA-3, a major product of immature granulocytes. A more liberal correction (Benjamini and Hochberg correction) yielded 18 additional genes, 12 of...
Subjects
Medical Subject Headings: skin and connective tissue diseases
free text keywords: Article, microarray, immature granulocytes, glucocorticoid, leukocytes, autoimmunity, Immunology, Immunology and Allergy, Autoimmune disease, medicine.disease, medicine, Lupus erythematosus, Defensin, Granulopoiesis, Molecular biology, Interferon, medicine.drug, Gene expression profiling, business.industry, business, Cytokine, medicine.medical_treatment, Leukopoiesis
Funded by
NIH| ECTOPIC GERMINAL CENTER REACTION IN SYSTEMIC LUPUS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R01AR046589-01
  • Funding stream: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
,
NIH| BAA-CLIN. TRIALS &CLIN. MARKERS FOR IMMUNILOGIC DISEASE-266005412
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: N01AI005412-005
  • Funding stream: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
44 references, page 1 of 3

1 Kammer, G.M., and G.C. Tsokos. 1999. Lupus: Molecular and Cellular Pathogenesis. Humana Press, Totowa, NJ. 728 pp.

2 Lahita, R.G. 1999. Systemic Lupus Erythematosus. Academic Press. 3rd edition. San Diego, CA. 1051 pp.

3 Wakeland, E.K., K. Liu, R.R. Graham, and T.W. Behrens. 2001. Delineating the genetic basis of systemic lupus erythematosus. Immunity. 15:397–408. 11567630 [PubMed]

4 Shlomchik, M.J., J.E. Craft, and M.J. Mamula. 2001. From T to B and back again: positive feedback in systemic autoimmune disease. Nat. Rev. Immunol. 1:147–153. 11905822 [PubMed]

5 Davidson, A., and B. Diamond. 2001. Autoimmune diseases. N. Engl. J. Med. 345:340–350. 11484692 [PubMed]

6 Freed, J.H., A. Marrs, J. VanderWall, P.L. Cohen, and R.A. Eisenberg. 2000. MHC class II-bound self peptides from autoimmune MRL/lpr mice reveal potential T cell epitopes for autoantibody production in murine systemic lupus erythematosus. J. Immunol. 164:4697–4705. 10779775 [PubMed]

7 Kaliyaperumal, A., M.A. Michaels, and S.K. Datta. 2002. Naturally processed chromatin peptides reveal a major autoepitope that primes pathogenic T and B cells of lupus. J. Immunol. 168:2530–2537. 11859148 [PubMed]

8 Lipsky, P.E. 2001. Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat. Immunol. 2:764–766. 11526379 [PubMed]

9 Arce, E., D.G. Jackson, M.A. Gill, L.B. Bennett, J. Banchereau, and V. Pascual. 2001. Increased frequency of pre-germinal center b cells and plasma cell precursors in the blood of children with systemic lupus erythematosus. J. Immunol. 167:2361–2369. 11490026 [PubMed]

10 Rubin, R.L., F.L. Tang, E.K. Chan, K.M. Pollard, G. Tsay, and E.M. Tan. 1986. IgG subclasses of autoantibodies in systemic lupus erythematosus, Sjogren's syndrome, and drug-induced autoimmunity. J. Immunol. 137:2528–2534. 3760566 [PubMed]

11 Casciola-Rosen, L.A., G. Anhalt, and A. Rosen. 1994. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J. Exp. Med. 179:1317–1330. 7511686 [OpenAIRE] [PubMed]

12 Amoura, Z., J.C. Piette, H. Chabre, P. Cacoub, T. Papo, B. Wechsler, J.F. Bach, and S. Koutouzov. 1997. Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus: correlation with serum antinucleosome antibody titers and absence of clear association with disease activity. Arthritis Rheum. 40:2217–2225. 9416860 [PubMed]

13 Banchereau, J., F. Briere, C. Caux, J. Davoust, S. Lebecque, Y. Liu, B. Pulendran, and K. Palucka. 2000. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18:767–811. 10837075 [PubMed]

14 Steinman, R.M., S. Turley, I. Mellman, and K. Inaba. 2000. The induction of tolerance by dendritic cells that have captured apoptotic cells. J. Exp. Med. 191:411–416. 10662786 [OpenAIRE] [PubMed]

15 Blanco, P., A.K. Palucka, M. Gill, V. Pascual, and J. Banchereau. 2001. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science. 294:1540–1543. 11711679 [OpenAIRE] [PubMed]

44 references, page 1 of 3
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