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Rex Neal Smith |
Assistant Pathologist |
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501 Warren Bldg |
Cardiovascular, Renal, Pulmonary, |
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Department of Pathology |
Transplantation and Autopsy Pathology |
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Massachusetts General Hospital |
Associate Director, Autopsy Service |
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Boston, MA 02421 |
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617-726-1835 |
smith.rex@mgh.harvard.edu |
Certification
American Board of Pathology, Anatomic and Clinical Pathology
American Board of Pathology, Immunopathology
Hospital Service
Clinical service includes cardiovascular, and pulmonary surgical pathology,
autopsy pathology, medical renal pathology and immunopathology including
ANCA, and flow cytometry.
Research
Research interests include transplantation pathology conducted at the
Massachusetts General Hospital and collaborative Harvard Hospitals.
Professional Societies and Memberships
American Association of Immunologists
USCAP
Renal Pathology Society
Fellow, College of American Pathology
American Society for Investigative Pathology
Society for Cardiovascular Pathology
International Society for Heart and Lung Transplantation
Transplantation Society
American Society of Transplantation
Original Articles
1. Rosner, W., S. Toppel, and R.N. Smith, 1974
Testosterone-estradiol-binding globulin of human plasma: denaturation and
protection. Biochim Biophys Acta. 351:92-8.
2. Powell, A.E., et al., 1975 Specific responsiveness of leukocytes to
soluble extracts of human tumors. Int J Cancer. 16:905-13.
3. Rosner, W. and R.N. Smith, 1975 Isolation and characterization of the
testosterone-estradiol-binding globulin from human plasma. Use of a novel
affinity column. Biochemistry. 14:4813-20.
4. Smith, R.N. and A.E. Powell, 1977 The adoptive transfer of
pregnancy-induced unresponsiveness to male skin grafts with thymus-dependent
cells. J Exp Med. 146:899-904.
5. Powell, A.E., A.M. Sloss, and R.N. Smith, 1978 Leukocyte-adherence
inhibition: a specific assay of cell-mediated immunity dependent on
lymphokine-mediated collaboration between T lymphocytes. J Immunol.
120:1957-66.
6. Powell, A., et al., 1979 Antigenic specificity and cellular mechanisms in
leukocyte adherence inhibition analysis of immunity to simple proteins and
hapten-protein conjugates. Cancer Res. 39:570-5.
7. Smith, R.N. and J.C. Howard, 1980 Heterogeneity of the tolerant state in
rats with long established skin grafts. J Immunol. 125:2289-94.
8. Smith, R.N., 1981 Inability of tolerant males to sire tolerant progeny.
Nature. 292:767-8.
9. Battisto, J.R., et al., 1982 Susceptibility to adjuvant arthritis in DA
and F344 rats. A dominant trait controlled by an autosomal gene locus linked
to the major histocompatibility complex. Arthritis Rheum. 25:1194-200.
10. Smith, R.N., et al., 1982 Discussion on: Beer, A.E., Quebbeman, J.F.,
Ayers, J.W.T., and Haines, F. 1981. Major histocompatibility complex
antigens, maternal, and paternal immune responses, and chronic habitual
abortion in humans. Amer, J. Obst. & Gyn. 141, 987, 1982. Amer. J. Obst. &
Gyn. 143:177.
11. Smith, R.N., R.T. Margolias, and M. Sternlicht, 1982 The alloantibody
response in the allogeneically pregnant rat. II. Primary pregnancy-induced
anti-RT1Aa alloantibodies are not as cross-reactive as secondary
pregnancy-induced or conventionally raised alloantibodies. J Immunol.
129:777-82.
12. Smith, R.N. and M. Sternlicht, 1982 The alloantibody response in the
allogeneically pregnant rat. III. The location of the alloantibody-forming
cells. J Immunol. 129:783-6.
13. Smith, R.N., M. Sternlicht, and G.W. Butcher, 1982 The alloantibody
response in the allogeneically pregnant rat. I. The primary and secondary
responses and detection of Ir gene control. J Immunol. 129:771-6.
14. Crowe, W.E., J.R. Battisto, and R.N. Smith, 1985 The autologous mixed
lymphocyte reaction is decreased in Freund's adjuvant-injected rats of
arthritis-susceptible and -insusceptible strains. Arthritis Rheum.
28:537-41.
15. Smith, R.N., et al., 1986 The alloantibody response in the
allogeneically pregnant rat. IV. Analysis of the alloantibody specificities
with monoclonal antibodies. J Immunol. 136:4063-9.
16. Amsden, A., et al., 1987 The alloantibody response in the allogeneically
pregnant rat. V. Absence of cell-mediated immunity in high responders. J
Reprod Immunol. 11:261-71.
17. Amsden, A.F., R.N. Smith, and N. Chirakalwasan, 1988 The alloantibody
response in the allogeneically pregnant rat. VI. Detection in maternal serum
of specific antigen-antibody complexes. J Immunol. 141:2295-302.
18. Hunt, J.S., et al., 1989 Products of lipopolysaccharide-activated
macrophages (tumor necrosis factor-alpha, transforming growth factor-beta)
but not lipopolysaccharide modify DNA synthesis by rat trophoblast cells
exhibiting the 80-kDa lipopolysaccharide-binding protein. J Immunol.
143:1606-13.
19. Meagher, R., et al., 1990 Placental CSF-like activity. Exp Hematol.
18:448-51.
20. Smith, R.N., et al., 1992 Multiple pathways in the rejection of skin
grafts. J Surg Res. 52:413-5.
21. Reese, T.G., et al., 1995 Imaging myocardial fiber architecture in vivo
with magnetic resonance. Magn Reson Med. 34:786-91.
22. Mizoguchi, A., et al., 1997 Suppressive role of B cells in chronic
colitis of T cell receptor alpha mutant mice. J Exp Med. 186:1749-56.
23. Ryan, E.T., et al., 1997 Protective immunity against Clostridium
difficile toxin A induced by oral immunization with a live, attenuated
Vibrio cholerae vector strain. Infect Immun. 65:2941-9.
24. Gilbert, R.J., et al., 1998 Determination of lingual myoarchitecture in
whole tissue by NMR imaging of anisotropic water diffusion. Am J Physiol.
275:G363-9.
25. Friedman, T., et al., 1999 Human CD4+ T cells mediate rejection of
porcine xenografts. J Immunol. 162:5256-62.
26. Friedman, T., et al., 1999 A critical role for human CD4+ T-cells in
rejection of porcine islet cell xenografts. Diabetes. 48:2340-8.
27. Imai, M., et al., 1999 Modulation of nucleoside [correction of
nucleotide] triphosphate diphosphohydrolase-1 (NTPDase-1)cd39 in xenograft
rejection. Mol Med. 5:743-52.
28. Lin, Y., et al., 1999 Accommodated xenografts survive in the presence of
anti-donor antibodies and complement that precipitate rejection of naive
xenografts. J Immunol. 163:2850-7.
29. Lin, Y., et al., 2000 Long-term survival of hamster hearts in
presensitized rats. J Immunol. 164:4883-92.
30. Sevigny, J., et al., 2000 Identification and characterization of a novel
hepatic canalicular ATP diphosphohydrolase. J Biol Chem. 275:5640-7.
31. Kawai, T., et al., 2001 Long-term islet allograft function in the
absence of chronic immunosuppression: a case report of a nonhuman primate
previously made tolerant to a renal allograft from the same donor.
Transplantation. 72:351-4.
32. Sato, K., et al., 2001 Carbon monoxide generated by heme oxygenase-1
suppresses the rejection of mouse-to-rat cardiac transplants. J Immunol.
166:4185-94.
33. Smith, R.N., L. Grazette, and S. Houser, 2001 Quilty lesions are
specific for cardiac allografts and not cyclosporine. Circulation.
104:479-480.
34. Abdi, R., et al., 2002 The role of CC chemokine receptor 5 (CCR5) in
islet allograft rejection. Diabetes. 51:2489-95.
35. Gunther, L., et al., 2002 Carbon monoxide protects pancreatic beta-cells
from apoptosis and improves islet function/survival after transplantation.
Diabetes. 51:994-9.
36. Makhlouf, L., et al., 2002 The role of autoimmunity in islet allograft
destruction: major histocompatibility complex class II matching is necessary
for autoimmune destruction of allogeneic islet transplants after T-cell
costimulatory blockade. Diabetes. 51:3202-10.
37. Medoff, B.D., et al., 2002 IFN-gamma-inducible protein 10 (CXCL10)
contributes to airway hyperreactivity and airway inflammation in a mouse
model of asthma. J Immunol. 168:5278-86.
38. Smith, R.N., et al., 2002 Higher frequency of high-grade rejections in
cardiac allograft patients after Quilty B lesions or grade 2/4 rejections.
Transplantation. 73:1928-32.
39. Wang, N., et al., 2002 Induction of xenograft accommodation by
modulation of elicited antibody responses. Transplantation. 74:334-45.
40. Ansari, M.J., et al., 2003 The programmed death-1 (PD-1) pathway
regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med.
198:63-9.
41. Koulmanda, M., et al., 2003 Effects of streptozotocin on autoimmune
diabetes in NOD mice. Clin Exp Immunol. 134:210-6.
42. Koulmanda, M., et al., 2003 The effect of low versus high dose of
streptozotocin in cynomolgus monkeys (Macaca fascilularis). Am J Transplant.
3:267-72.
43. Koulmanda, M., et al., 2003 Pig islet xenografts are resistant to
autoimmune destruction by non-obese diabetic recipients after anti-CD4
treatment. Xenotransplantation. 10:178-84.
44. Otterbein, L.E., et al., 2003 Carbon monoxide suppresses
arteriosclerotic lesions associated with chronic graft rejection and with
balloon injury. Nat Med. 9:183-90.
45. Tseng, W.Y., et al., 2003 Diffusion tensor MRI of myocardial fibers and
sheets: correspondence with visible cut-face texture. J Magn Reson Imaging.
17:31-42.
46. Abdi, R., et al., 2004 Differential role of CCR2 in islet and heart
allograft rejection: tissue specificity of chemokine/chemokine receptor
function in vivo. J Immunol. 172:767-75.
47. Kawai, T., et al., 2004 CD154 blockade for induction of mixed chimerism
and prolonged renal allograft survival in nonhuman primates. Am J
Transplant. 4:1391-8.
48. Koulmanda, M., et al., 2004 Prolonged survival of fetal pig islet
xenografts in mice lacking the capacity for an indirect response.
Xenotransplantation. 11:525-30.
49. Koyama, I., et al., 2004 Thrombophilia associated with anti-CD154
monoclonal antibody treatment and its prophylaxis in nonhuman primates.
Transplantation. 77:460-2.
50. Nikolic, B., et al., 2004 Mixed hematopoietic chimerism allows cure of
autoimmune diabetes through allogeneic tolerance and reversal of
autoimmunity. Diabetes. 53:376-83.
51. Yamashita, K., et al., 2004 Biliverdin, a natural product of heme
catabolism, induces tolerance to cardiac allografts. Faseb J. 18:765-7.
52. Smith, R.N., et al., 2005 C4d deposition in cardiac allografts
correlates with alloantibody. J Heart Lung Transplant. 24:1202-10.
53. Baggish, A.L., et al., 2006 Pathological effects of alcohol septal
ablation for hypertrophic obstructive cardiomyopathy. Heart. 92:1773-8.
54. Boskovic, S., et al., 2006 Monitoring antidonor alloantibodies as a
predictive assay for renal allograft tolerance/long-term observations in
nonhuman primates. Transplantation. 82:819-25.
55. Cilmi, S.A., et al., 2006 Fabry disease in mice protects against lethal
disease caused by Shiga toxin-expressing enterohemorrhagic Escherichia coli.
J Infect Dis. 194:1135-40.
56. Fiorina, P., et al., 2006 Role of CXC chemokine receptor 3 pathway in
renal ischemic injury. J Am Soc Nephrol. 17:716-23.
57. Koulmanda, M., et al., 2006 Prolonged survival of allogeneic islets in
cynomolgus monkeys after short-term anti-CD154-based therapy: nonimmunologic
graft failure? Am J Transplant. 6:687-96.
58. Shimizu, I., et al., 2006 Decay-accelerating factor prevents acute
humoral rejection induced by low levels of anti-alphaGal natural antibodies.
Transplantation. 81:95-100.
59. Smith, R.N., et al., 2006 Chronic antibody mediated rejection of renal
allografts: pathological, serological and immunologic features in nonhuman
primates. Am J Transplant. 6:1790-8.
60. Yamashita, K., et al., 2006 Heme oxygenase-1 is essential for and
promotes tolerance to transplanted organs. Faseb J. 20:776-8.
61. Fiorina, P., et al., 2007 Characterization of donor dendritic cells and
enhancement of dendritic cell efflux with CC-chemokine ligand 21: a novel
strategy to prolong islet allograft survival. Diabetes. 56:912-20.
62. Izawa, A., et al., 2007 Importance of donor- and recipient-derived
selectins in cardiac allograft rejection. J Am Soc Nephrol. 18:2929-36.
63. Koyama, I., et al., 2007 Depletion of CD8 Memory T Cells for Induction
of Tolerance of a Previously Transplanted Kidney Allograft. Am J Transplant.
7:1055-61.
64. Lacy-Hulbert, A., et al., 2007 Beta 3 integrins regulate lymphocyte
migration and cytokine responses in heart transplant rejection. Am J
Transplant. 7:1080-90.
65. Smith, R.N., et al., 2007 Chemokines and chronic heart allograft
rejection. Transplantation. 84:442-4.
66. Veronese, F., et al., 2007 Pathological and Clinical Correlates of FOXP3
Cells in Renal Allografts during Acute Rejection. Am J Transplant.
67. Ansari, M.J., et al., 2008 Role of ICOS pathway in autoimmune and
alloimmune responses in NOD mice. Clin Immunol. 126:140-147.
68. Kunzli, B.M., et al., 2008 Disordered pancreatic inflammatory responses
and inhibition of fibrosis in CD39-null mice. Gastroenterology. 134:292-305.
69. Smith, R.N., et al., 2008 Four stages and lack of stable accommodation
in chronic alloantibody-mediated renal allograft rejection in Cynomolgus
monkeys. Am J Transplant. 8:1662-72.
70. Smith, R.N., et al., 2008 Pathology of an islet transplant 2 years after
transplantation: evidence for a nonimmunological loss. Transplantation.
86:54-62.
71. Solez, K., et al., 2008 Banff 07 classification of renal allograft
pathology: Updates and future directions. American Journal of
Transplantation. 8:1-8.
72. Collins, A.B., R.N. Smith, and J.R. Stone, 2009 Classification of
amyloid deposits in diagnostic cardiac specimens by immunofluorescence.
Cardiovasc Pathol. 18:205-16.
73. Fiorina, P., et al., 2009 Immunomodulatory function of bone
marrow-derived mesenchymal stem cells in experimental autoimmune type 1
diabetes. J Immunol. 183:993-1004.
74. Ueno, T., et al., 2009 Divergent role of donor dendritic cells in
rejection versus tolerance of allografts. J Am Soc Nephrol. 20:535-44.
75. Seixas E, Gozzelino R, Chora A, Ferreira A, Silva G, Larsen R, Rebelo S,
Penido C, Smith RN, Coutinho A, Soares MP. Heme oxygenase-1 affords
protection against noncerebral forms of severe malaria. Proc Natl Acad Sci U
S A. 2009; 106 (37): 15837 - 15842.
76. Pakki Venkata UR, Callum M, Neuman M, Smith RN, and Trebbin W.
Lymphaticourinary fistula causing chyluria and nephrotic-range proteinuria.
2009; Am J Kidney Dis 53:A33-34
77. Nikolic B, Onoe T, Takeuci Y, Khalpey A, Primo V, Leykin I, Smith RN,
Sykes M. Distinct requirements for achievement of allotolerance versus
reversal of autoimmunity via non-myeloablative mixed chimerism induction in
NOD mice. Transplantation, in press.
78. Primo VC, Marusic S, Franklin CC, Goldman WH, Achaval CG, Smith RN,
Arnaout MA, NikolicB. Anti-PR3 immune responses induce segmental and
necrotizing glomerulonephritis. Clinical and Experimental Immunology, in
press.
Clinical Communications: Case records of the Massachusetts General
Hospital. Weekly Clinicopathological Exercises
1.Gorbach, S.L., Graeme-Cook, F., and Smith, R.N. 1994. Case 25-1994. A
58-year-old woman with bloody diarrhea after chemotherapy for carcinoma of
the tongue. New England Journal of Medicine 330: 1811-1817.
2.Hauser, S.C. and Smith, R.N. 1995. Case 40-1995. A 71-year-old woman with
right-lower quadrant pain and a cecal mass. New England Journal of Medicine
333:1764-1769.
3.Ives, D. and Smith, R.N. 1996. Case 17-1996. A 48-year-old man with the
acquired immunodeficiency syndrome, abdominal pain, and bloody diarrhea. New
England Journal of Medicine 334:1461-1467.
4.Sheets, E. and Smith, R.N. 1998. Case 3-1998. A 31-year-old woman with a
pleural effusion, ascites, and persistent fever spikes. New England Journal
of Medicine 338:248-254.
5.Ludmir, J. and Smith, R.N. 1998. Case 30-1998. A 30-year-old woman with
increasing hypertension and proteinuria. New England Journal of Medicine
339:906-913.
6.DiSalvo, T.G., King, M.E. and Smith, R.N. 2000. Case 3-2000. A 66-year-old
woman with diabetes, coronary disease, orthostatic hypotension and the
nephrotic syndrome. New England Journal of Medicine 342:264-273.
7.Helfgott, S.M. and Smith, R.N. 2002. Case 21-2002. A 21-Year-Old Man with
Arthritis during Treatment for Hyperthyroidism. New England Journal of
Medicine 347:122-309.
8.Bloom, B. and Smith, R.N. 2003. Case 29-2002. A 17 year old boy with
mitral regurgitation and pulmonary edema. New England Journal of Medicine
347:921-928.
9.Ronthal, M., Smith, R.N., Frosch, M. 2003. A 72-year old right-handed man
was admitted to the hospital because of recurrent neurological symptoms. New
England Journal of Medicine 349:170-180.
10.Medoff BD, Shepard JA, Smith, R.N., and Kratz A. 2005. Case 17-2005. A
22-year-old women with back and leg pain and respiratory failure. New
England Journal of Medicine 352:2425-2434.
11.Wolf, M, Rose, H, and Smith, R.N. 2005. Case 28-2005: A 42-year-old man
with weight loss, weakness, and a rash. New England Journal of Medicine
353:1148-1157.
Reviews
1. Rosner, W. and Smith, R.N. 1975. Isolation of testosterone estradiol
binding globulin. In: Methods in Enzymology, 36:109-120. Academic Press.
2. Smith, R.N., Amsden, A., Sudilovsky, O., Coleman, N. and Margolies, R.
1986. Analysis with monoclonal antibodies of the alloantibody response in
the allogeneically pregnant rat. In: Immunoregulation and Fetal Survival.
Ed. T. Wegman & T. Gill. Oxford Univ. Press.
3. Bhan, A.K., Mizoguchi, E., Smith, R.N. and Mizoguchi, A. 1999. Colitis in
Transgenic and Knockout Mice as a Model Human Inflammatory Bowel Disease.
Immunological Reviews.169:195-207.
4. Bhan, A.K., Mizoguchi, E., Smith, R.N. and Mizoguchi, A. 1999.
Experimental Models of Intestinal Inflammation: Lesson from Human IBD.
Current Opinion in Gastroenterology. 15:285-290.
5. Bhan, A.K., Mizoguchi, E., Smith, R.N., Mizoguchi, A. 2000. Spontaneous
chronic colitis in TCR alpha-mutant mice; an experimental model of human
ulcerative colitis. International Reviews of Immunology. 19:123-138.
6. Soares, M.P., Brouard, S., Smith, R.N., Otterbein, L., Choi, A.M. and
Bach, F.H. Expression of heme oxygenase-1 by endothelial cells: a protective
response to injury in transplantation. 2000. Expert Opinion on Therapeutic
Targets 4: 11.
7. Soares, M.P., Brouard, S., Smith, R.N., and Bach, F.H. 2001. Heme
oxygenase-1, a protective gene that can protect organs from rejection.
Immunological Reviews. 184:275-285.
8. Colvin, R.B. and Smith, R.N. 2005. Antibody-Mediated Organ Allograft
Rejection. Nature Reviews Immunology 5:807-817.
9. Cornell, L.D., Smith, R.N. and Colvin, R.B. 2008. Kidney Transplantation:
Mechanisms of Rejection and Acceptance. Annual Review of Pathology:
Mechanisms of Disease. 3: 189 - 220.