Chaperones and Disease
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In Table 3 of their excellent review, Macario and Conway de Macario (Oct. 6 issue)1 state that an elevated level of circulating heat-shock protein (HSP) 70 has not been associated with any disease. However, we recently described elevated levels of circulating HSP70 in sickle cell disease.2 The increase in the level of HSP70 probably contributes to cytokine activation, since the protein may be released as a consequence of cell damage resulting from repeated episodes of ischemia–reperfusion injury.3,4
Adeboye H. Adewoye, M.D.
Boston Medical Center
Boston, MA 02118
hadewoye@bu.edu
Lillian McMahon, M.D.
Center of Excellence in Sickle Cell Disease
Boston, MA 02118
References
Macario AJL, Conway de Macario E. Sick chaperones, cellular stress, and disease. N Engl J Med 2005;353:1489-1501.
Adewoye AH, Klings ES, Farber HW, et al. Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70. Am J Hematol 2005;78:240-242.
Osarogiagbon UR, Choong S, Belcher JD, Vercellotti GM, Paller MS, Hebbel RP. Reperfusion injury pathophysiology in sickle transgenic mice. Blood 2000;96:314-320.
Asea A, Rehli M, Kabingu E, et al. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 2002;277:15028-15034.
To the Editor: With regard to their insightful overview of the possible roles of aberrant molecular chaperones in disease states, Macario and Conway de Macario mention that an increase in neuronal expression of glucose-regulated protein 78 (Grp78), a member of the HSP70 family, is associated with Alzheimer's disease. They also note that autoantibodies to specific chaperones may be correlated with certain disease states and cite an association of autoantibodies to HSP47 with autoimmune disease and autoantibodies to HSP60 and HSP70 with hearing loss. We would like to mention that autoantibodies to Grp78 are associated with metastatic androgen-independent prostate cancer.1 The origin of anti-Grp78 antibodies in prostate cancer is unclear but may involve the up-regulation of cell-surface expression of Grp78 on prostate-cancer cells.
John C. Mavropoulos, M.P.H.
Timothy A. Fields, M.D., Ph.D.
Salvatore V. Pizzo, M.D., Ph.D.
Duke University Medical Center
Durham, NC 27710
jcm10@duke.edu
References
Mintz PJ, Kim J, Do KA, et al. Fingerprinting the circulating repertoire of antibodies from cancer patients. Nat Biotechnol 2003;21:57-63.
To the Editor: Macario and Conway de Macario omitted the connection between HSP90 and systemic lupus erythematosus. Levels of HSP90 are elevated in some patients with this disorder, especially those with neuropsychiatric and cardiorespiratory manifestations of the disease.1 Although HSP90 is an intracellular chaperone, it is expressed on the surface of mononuclear cells in patients with systemic lupus erythematosus who have a high level of disease activity.2 Autoantibodies against HSP90 were detected in a proportion of patients with systemic lupus erythematosus who have renal disease and a low C3 level.3
Yair Levy, M.D.
Alexander Gorshtein, M.D.
Meir Medical Center
55900 Kfar Saba, Israel
levy.yair@clalit.org.il
References
Dhillon VB, McCallum S, Latchman DS, Isenberg DA. Elevation of the 90 kDa heat-shock protein in specific subsets of systemic lupus erythematosus. Q J Med 1994;87:215-222.
Erkeller-Yuksel FM, Isenberg DA, Dhillon VB, Latchman DS, Lydyard PM. Surface expression of heat shock protein 90 by blood mononuclear cells from patients with systemic lupus erythematosus. J Autoimmun 1992;5:803-814.
Conroy SE, Faulds GB, Williams W, Latchman DS, Isenberg DA. Detection of autoantibodies to the 90 kDa heat shock protein in systemic lupus erythematosus and other autoimmune diseases. Br J Rheumatol 1994;33:923-926.
The authors reply: In our short review, as noted by the correspondents, many publications could not be cited. Drs. Adewoye and McMahon say that we state in Table 3 of our article that an elevated level of circulating HSP70 has not been associated with any disease. What is actually meant in the row in our table pertaining to HSP70 (from data by Jin et al.1) is that these authors found the chaperone in serum from healthy men. They reported that HSP70 in serum was not associated with any syndrome or disease in the persons they studied. Other investigators have found HSP70 in serum in association with pathologic conditions, as Drs. Adewoye and McMahon have done. For example, Njemini et al.2 reported that in elderly people, HSP70 in serum was associated with inflammatory syndromes.Investigations should continue to elucidate why and by what mechanism chaperones appear in biologic fluids and whether these extracellular chaperones are initiators of autoimmune pathogenesis or are useful disease markers.
Alberto J.L. Macario, M.D.
Everly Conway de Macario, Ph.D.
New York State Department of Health
Albany, NY 12201
macario@wadsworth.org
References
Jin X, Wang R, Xiao C, et al. Serum and lymphocyte levels of heat shock protein 70 in ageing: a study in the normal Chinese population. Cell Stress Chaperones 2004;9:69-75.
Njemini R, Demanet C, Mets T. Inflammatory status as an important determinant of heat shock protein 70 serum concentrations during aging. Biogerontology 2004;5:31-38.
Adeboye H. Adewoye, M.D.
Boston Medical Center
Boston, MA 02118
hadewoye@bu.edu
Lillian McMahon, M.D.
Center of Excellence in Sickle Cell Disease
Boston, MA 02118
References
Macario AJL, Conway de Macario E. Sick chaperones, cellular stress, and disease. N Engl J Med 2005;353:1489-1501.
Adewoye AH, Klings ES, Farber HW, et al. Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70. Am J Hematol 2005;78:240-242.
Osarogiagbon UR, Choong S, Belcher JD, Vercellotti GM, Paller MS, Hebbel RP. Reperfusion injury pathophysiology in sickle transgenic mice. Blood 2000;96:314-320.
Asea A, Rehli M, Kabingu E, et al. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 2002;277:15028-15034.
To the Editor: With regard to their insightful overview of the possible roles of aberrant molecular chaperones in disease states, Macario and Conway de Macario mention that an increase in neuronal expression of glucose-regulated protein 78 (Grp78), a member of the HSP70 family, is associated with Alzheimer's disease. They also note that autoantibodies to specific chaperones may be correlated with certain disease states and cite an association of autoantibodies to HSP47 with autoimmune disease and autoantibodies to HSP60 and HSP70 with hearing loss. We would like to mention that autoantibodies to Grp78 are associated with metastatic androgen-independent prostate cancer.1 The origin of anti-Grp78 antibodies in prostate cancer is unclear but may involve the up-regulation of cell-surface expression of Grp78 on prostate-cancer cells.
John C. Mavropoulos, M.P.H.
Timothy A. Fields, M.D., Ph.D.
Salvatore V. Pizzo, M.D., Ph.D.
Duke University Medical Center
Durham, NC 27710
jcm10@duke.edu
References
Mintz PJ, Kim J, Do KA, et al. Fingerprinting the circulating repertoire of antibodies from cancer patients. Nat Biotechnol 2003;21:57-63.
To the Editor: Macario and Conway de Macario omitted the connection between HSP90 and systemic lupus erythematosus. Levels of HSP90 are elevated in some patients with this disorder, especially those with neuropsychiatric and cardiorespiratory manifestations of the disease.1 Although HSP90 is an intracellular chaperone, it is expressed on the surface of mononuclear cells in patients with systemic lupus erythematosus who have a high level of disease activity.2 Autoantibodies against HSP90 were detected in a proportion of patients with systemic lupus erythematosus who have renal disease and a low C3 level.3
Yair Levy, M.D.
Alexander Gorshtein, M.D.
Meir Medical Center
55900 Kfar Saba, Israel
levy.yair@clalit.org.il
References
Dhillon VB, McCallum S, Latchman DS, Isenberg DA. Elevation of the 90 kDa heat-shock protein in specific subsets of systemic lupus erythematosus. Q J Med 1994;87:215-222.
Erkeller-Yuksel FM, Isenberg DA, Dhillon VB, Latchman DS, Lydyard PM. Surface expression of heat shock protein 90 by blood mononuclear cells from patients with systemic lupus erythematosus. J Autoimmun 1992;5:803-814.
Conroy SE, Faulds GB, Williams W, Latchman DS, Isenberg DA. Detection of autoantibodies to the 90 kDa heat shock protein in systemic lupus erythematosus and other autoimmune diseases. Br J Rheumatol 1994;33:923-926.
The authors reply: In our short review, as noted by the correspondents, many publications could not be cited. Drs. Adewoye and McMahon say that we state in Table 3 of our article that an elevated level of circulating HSP70 has not been associated with any disease. What is actually meant in the row in our table pertaining to HSP70 (from data by Jin et al.1) is that these authors found the chaperone in serum from healthy men. They reported that HSP70 in serum was not associated with any syndrome or disease in the persons they studied. Other investigators have found HSP70 in serum in association with pathologic conditions, as Drs. Adewoye and McMahon have done. For example, Njemini et al.2 reported that in elderly people, HSP70 in serum was associated with inflammatory syndromes.Investigations should continue to elucidate why and by what mechanism chaperones appear in biologic fluids and whether these extracellular chaperones are initiators of autoimmune pathogenesis or are useful disease markers.
Alberto J.L. Macario, M.D.
Everly Conway de Macario, Ph.D.
New York State Department of Health
Albany, NY 12201
macario@wadsworth.org
References
Jin X, Wang R, Xiao C, et al. Serum and lymphocyte levels of heat shock protein 70 in ageing: a study in the normal Chinese population. Cell Stress Chaperones 2004;9:69-75.
Njemini R, Demanet C, Mets T. Inflammatory status as an important determinant of heat shock protein 70 serum concentrations during aging. Biogerontology 2004;5:31-38.