David Miklos

Clinical Focus

• Cancer > Bone Marrow Transplant
• Cancer > Hematology
• Aplastic Anemia
• Blood Stem Cell Transplant
• Blood and Marrow Transplantation

Administrative Appointments

• Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease, NIH (2004 - present)

Honors and Awards

• Clinical Investigator Training Program Scholar, Harvard Medical School (2001-2003)
• Medical Scientist Training Fellow, NIH (1993-1995)
• Predoctoral Fellow, Howard Hughes Medical Institute (1989-1993)
• Alpha Omega Alpha, Yale Medical School (1995)
• Phi Betta Kappa, University of Notre Dame (1987)

Professional Education

Postdoctoral Advisees

Persis Wadia

Graduate & Fellowship Program Affiliations

• Immunology
• Medicine

Web Site Links

• Bone Marrow Transplantation Site

Research Interests

Allogeneic hematopoietic stem cell transplantation (HSCT) can cure hematologic malignancies. Beneficial alloimmune responses target mHA expressed on hematopoietic tumor cells resulting in graft versus leukemia (GVL) and contribute to the eradication of malignant cells following transplantation. However, when donor T cells target mHA expressed by normal recipient tissues, patients suffer graft-versus-host disease (GVHD). A more extensive characterization of human mHA will establish which mHA mediate GVHD and/or GVL. Thus far, mHA identification has relied on allo-reactive T cells. However, our research has demonstrated that HSCT patients develop clinically relevant allogeneic B cell responses.
1. Antibody Responses to H-Y minor histocompatibility antigens are induced 4-8 months after allogeneic stem cell transplantation and in 40% of normal female donors. In order to determine if antibody responses to mHA occur after HSCT, we focused on H-Y antigens. Males develop tolerance to these self-antigens, but female T cells are capable of recognizing peptides derived from H-Y proteins following transplantation into male recipients. We established a sensitive ELISA to measure antibody responses to 5 recombinant H-Y proteins (DBY, UTY, ZFY, RPS4Y, and EIF1AY) and their X-homologs. Antibodies to at least one H-Y protein were present in 39 of 75 (52%) male HSCT patients with female donors (F-->M HSCT).
2. H-Y antigen DBY elicits a coordinated B and T cell response after allogeneic HSCT. Unstimulated PBMC from a F-->M HSCT patient identified a CD4+ T cell response by ELISpot to a single DBY peptide that persisted for more than a 1-year period after transplant. The T cell epitope was identified as a 19-mer peptide starting at position 30 in the DBY sequence (DBY30-48) and restricted by HLA-DRB1*1501. Remarkably, the corresponding X homolog peptide (DBX30-48) was also recognized by female donor T cells. However this patient developed antibodies after HSCT...

Clinical Trials

• A Phase II Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft versus Host Disease Recruiting
• Bone Marrow Grafting for Leukemia and Lymphoma Recruiting
• NMDP Research Database for Allogeneic Unrelated Hematopoietic Stem Cell Transplantation Recruiting
• Allogeneic HCT using Nonmyeloablative Host Conditioning with TLI & ATG vs SOC in AML Recruiting
• Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma Recruiting

Publications

• Protein microarrays identify antibodies to protein kinase Czeta that are associated with a greater risk of allograft loss in pediatric renal transplant recipients. Sutherland SM, Li L, Sigdel TK, Wadia PP, Miklos DB, Butte AJ, Sarwal MM. Kidney Int. 2009
• TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Kohrt HE, Turnbull BB, Heydari K, Shizuru JA, Laport GG, Miklos DB, Johnston LJ, Arai S, Weng WK, Hoppe RT, Lavori PW, Blume KG, Negrin RS, Strober S, Lowsky R. Blood. 2009; 114 (5): 1099-109
• H-Y antibody development associates with acute rejection in female patients with male kidney transplants. Tan JC, Wadia PP, Coram M, Grumet FC, Kambham N, Miller K, Pereira S, Vayntrub T, Miklos DB. Transplantation. 2008; 86 (1): 75-81
• Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Miklos DB, Kim HT, Miller KH, Guo L, Zorn E, Lee SJ, Hochberg EP, Wu CJ, Alyea EP, Cutler C, Ho V, Soiffer RJ, Antin JH, Ritz J. Blood. 2005; 105 (7): 2973-8
• Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation. Zorn E, Miklos DB, Floyd BH, Mattes-Ritz A, Guo L, Soiffer RJ, Antin JH, Ritz J. J Exp Med. 2004; 199 (8): 1133-42