Rheumatology

Alexei Grom, MD

Appointment

Research Assistant Professor of Pediatrics

Email

alexei.grom@cchmc.org

Phone

513-636-3339

Fax

513-636-3328

Bio

The research of Alexei Grom, MD, has mainly involved two translational projects focused on two autoimmune diseases – systemic juvenile rheumatoid arthritis and juvenile dermatomyositis. In both projects, recent advances of cellular immunology are applied to these diseases to promote better understanding of their pathogenesis and treatment.

Systemic Onset Juvenile Rheumatoid Arthritis and an associated condition known as Macrophage Activation Syndrome are severe and often devastating illnesses. The pathological mechanisms are not known but Dr. Alexei Grom has focused his research on NK and cytotoxic cell function in this disease. The rationale for this approach has been based on the strong clinical similarities between MAS and the better understood autosomal recessive disorder familial hemophagocytic lymphohistiocytosis, in which the uncontrolled proliferation of T cells and macrophages has been recently associated with decreased NK cell and cytotoxic cell functions secondary to mutations in the gene encoding perforin. Recent observations suggest as in FHLH, MAS patients also have profoundly depressed NK function. Moreover, a large subgroup of systemic JRA patients has very similar immunologic abnormalities. Combined with the evidence of the immunoregulatory role of NK cells in many immune responses, this suggests that NK dysfunction is relevant to the pathogenesis of MAS. New directions have thus been established for research in this poorly understood disease.

Juvenile Dermatomyositis is a chronic inflammatory condition involving primarily muscles and skin. The most characteristic feature of JDM is vascular damage associated with the capillary necrosis that eventually leads to capillary loss and tissue ischemia. The project is based on the hypothesis that capillary loss in this condition may be caused by angiostatic chemokines that are prominent in the inflammatory response in the affected muscles.

Credentials

MD: Leningrad (St. Petersburg) Pediatric Medical Institute, Russia, 1986.

Residency: Pediatrics, Leningrad (St. Petersburg) Medical Institute, Russia, 1988; Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio, 1998.

Fellowship: Pediatric Rheumatology, Leningrad (St. Petersburg) Pediatric Medical Institute, Russia, 1991; Pediatric Rheumatology, Children's Hospital Medical Center, Cincinnati, Ohio, 1995.

Certification: Pediatrics, 1999.

Position History

1986-1988 Clinical Residency in Pediatrics, Leningrad Pediatric Medical Institute, Leningrad, USSR
1988-1991 Postdoctoral Clinical Fellowship in Pediatric Rheumatology, Dept of Children's Diseases #3, Leningrad Pediatric Medical Institute, Leningrad, USSR
1991-1995 Postdoctoral Research Fellowship, Pediatric Rheumatology, Children's Hospital Medical Center, and University of Cincinnati, Cincinnati, Ohio
1995 – 1997 Postdoctoral Clinical Fellowship, Pediatric Rheumatology, Children's Hospital Medical Center, Cincinnati, Ohio
1997 – 1998 Clinical Residency in Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio
1998 – 2001 Research Instructor, Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio
2001 – 2005 Research Assistant Professor of Pediatrics, Children's Hospital Medical Center, and College of Medicine, University of Cincinnati, Cincinnati, Ohio
2005 - Research Associate Professor of Pediatrics, Children's Hospital Medical Center, and College of Medicine, University of Cincinnati, Cincinnati, Ohio

Awards and Honors

Arthritis Foundation Fellowship
American College of Rheumatology, Senior Scholar Award
American College of Rheumatology, Pediatric Section Award for the best laboratory science abstract
Procter Scholarship, Children's Hospital Research Foundation, Cincinnati, Children's Hospital Research Foundation, Cincinnati, Ohio

Research

Dr. Grom's research has mainly involved two translational projects focused on two autoimmune diseases – systemic juvenile rheumatoid arthritis and juvenile dermatomyositis. In both projects, recent advances of cellular immunology are applied to these diseases to promote better understanding of their pathogenesis and treatment.

Moreover, a large subgroup of systemic JRA patients has very similar immunologic abnormalities. Combined with the evidence of the immunoregulatory role of NK cells in many immune responses, this suggests that NK dysfunction is relevant to the pathogenesis of MAS. New directions have thus been established for research in this poorly understood disease.

Research Grants and Contracts

Active

PO1-AR048929 Program Project Grant (Glass)
07/01/03 - 06/30/08
Project #4 PI :Grom
NIH
Gene Expression Profiles in Systemic Onset Juvenile Rheumatoid Arthritis and Macrophage Activation Syndrome (Grom)
The project is focused on the identification of gene expression profiles that would distinguish clinical subgroups of patients with systemic JRA and predict long-term clinical outcomes in these patients.

U01 UA1067150A (Grom, Co-Investigator)
9/30/2005-3/10-2010
NIH/NIAID
"HLA/KIR Region Genetics in Pediatric Arthritis"

Completed in the past three years

R21 AR508281 (Grom)
09/30/03 - 09/30/05
NIH/NIAMS
"Pathogenic Mechanisms of the Vasculopathy of JDM"
The project is focused on the role of the angiostatic component of the inflammatory response in the poor vascular repair in JDM.

P30-AR47363 (Thompson)
03/15/01 - 02/28/04
NIH
P & F Project #1 in Cincinnati Rheumatic Diseases Core Center
Project PI: Grom
"Interleukin 15 and vascular endothelial cell activation in JRA synovium".
The project is based on the hypothesis that IL-15 plays a central role in VEC activation and vascularization of the pannus tissue in JRA. The major long-term goal of this study is to elucidate the role of IL-15 in JRA synovium.

Translational Research Grant (PI Grom)
07/01/02 - 06/30/03
Cincinnati Children's Hospital Medical Center
"Natural Killer Cell Dysfunction in Patients with Systemic Onset JRA and Macrophage Activation Syndrome"
The main goal of this proposal is to assess clinical and pathogenic significance of natural killer cell dysfunction in patients with macrophage activation syndrome and systemic onset juvenile rheumatoid arthritis.

Publications, Most Recent

Barnes M, Aronow B, Luyrink L, Moroldo M, Pavlidis P, Passo MH, Grom AA, Hirsch R, Giannini EH, Colbert R, Glass DN, and Thompson S. Gene Expression in Juvenile Arthritis and Spondyloarthropathy: Pro-angiogenic ELR+ Chemokine Genes Relate to Course of Arthritis.Rheumatology (Oxford) 2004;43:973-9.

Grom AA. NK dysfunction: a common pathway in systemic onset juvenile rheumatoid arthritis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis.Arthritis Rheum 2004:50;689-98.

Grom AA: Macrophage activation syndrome.In: Isenberg DA, Maddison PJ, Glass DN, Woo P, Breedveld FC (eds.)Oxford Textbook of Rheumatology, Third Edition, Oxford University Press, Oxford, 2004, (Chapter 6.12.7).

Barron A, Lee T-L, Taylor J, Moore T, Passo MH, Graham TB, Griffin T, Grom AA, Lovell DJ, and Brunner H. Feasibility and construct validity of the Willingness-To-Pay (WTP) technique for measuring health care preferences in children with juvenile idiopathic arthritis.Arthritis Care & Res 2004;51:899-908.

Villanueva J, Lee S, Giannini EH, Graham TB, Passo MH, Filipovich AH, and Grom AA. Natural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome.Arthritis Res Ther 2005;7:R30-37.

Herman LM, Pinkerton M, Jennings, Yang L, Grom AA, Sowders D, Kersten S, Witte D, Hirsch R, Thornton S. Angiopoietin-Like-4 is a potential angiogenic mediator in arthritis.Clin Immunol 2005;115:93-101.

Ramanan AV, Grom AA. Does systemic onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis?Rheumatology (Oxford) 2005;44:1350-3.

Fall N, Bove KE, Stringer K, Lovell DJ, Brunner HI, Ilowite NT, Higgins GC, Bowyer SL, Graham TB, Thornton S, and Grom AA: Lack of Angiogenic Response in Muscle Tissues from Patients with Juvenile Dermatomyositis is Associated with High Expression of Angiostatic ELR-negative CXC-Chemokines: Possible Link to Vasculopathy.Arthritis Rheum 2005;52:3175-80.

Grom AA. Fever and the inflammatory response.In: Long, Pickering, and Prober (eds) Principles and Practice of Pediatric Infectious Diseaseas, Third Edition, Elsevier, New York, 2006 (Chapter 11), in press.

Brunner HI, Mueller M, Rutherford C, Passo MH, Grom AA, Mishra J, Devarajan P: Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) as a Biomarker of Nephritis in Childhood-onset Systemic Lupus Erythematosus.Arthritis Rheum 2006, 54(8): 2577-2584.

Invited Papers

Grom AA, Giannini EH, Glass DN: JRA and the trimolecular complex: HLA, TCR and antigen. Differences from rheumatoid arthritis (RA).Arthritis & Rheum 1994; 37:601-607.

Grom AA, Passo MH: Macrophage activation syndrome in systemic juvenile rheumatoid arthritis.J Pediatr 129:630-2, 1996.

Grom AA, Glass DN: Juvenile Rheumatoid Arthritis. In: Frank MM, Austen KF (eds) Samter's Immunologic Basis of Disease, Sixth Edition, Lippincott Williams & Wilkins, Philadelphia, 2000, pp 463-75 (Chapter 38).

Grom AA, Hirsch R: T-cell and T-cell receptor abnormalities in the immunopathogenesis of juvenile rheumatoid arthritis. Current Opinion in Rheumatology, 2000;12:420-24.

Grom AA: Macrophage activation syndrome.In:Isenberg DA, Maddison PJ, Glass DN, Woo P, Breedveld FC (eds.) Oxford Textbook of Rheumatology, Third Edition, Oxford University Press, Oxford, 2001, (Chapter 6.12.7), (in press).

Grom AA, Glass DN: Etiology and pathogenesis of juvenile chronic arthritis. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH (eds) Rheumatology, Third Edition, Mosby, London, 2002 (Chapter 68).

Grom AA: Macrophage activation syndrome and reactive hemophagocytic lymphohistiocytosis: the same entities?Current Opinion in Rheumatology, 2003:15;587-90.

Villanueva J, Lee S, Giannini EH, Graham TB, Passo MH, Filipovich AH, and Grom AA: Natural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome.Arthritis Research & Therapy, 2005;7:R30-37.

Barron A, Lee T-L , Taylor J, Moore T, Passo MH, Graham TB, Griffin T, Grom AA, Lovell DJ, and Brunner H. Feasibility and construct validity of the Willingness-To-Pay (WTP) technique for measuring health care preferences in children with juvenile idiopathic arthritis.Arthritis Care & Res 2004;51:899-908.

Ramanan AV, Grom AA. Does systemic onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis?Rheumatology (Oxford) 2005 (pre-published on-line).