A series of monoclonal antibodies were raised by immunization with a malignant human lymphoblastoid T cell line. This panel includes antibodies specific for differentiation-associated antigens expressed either by basal keratinocytes; by the stratum corneum and cells in the stratum granulosum; or by all epidermal keratinocytes. Further characterization of their tissue distribution will be performed by immunoperoxidase studies of tissue sections, and immunofluorescence studies of lymphoid cells and keratinocytes in vitro. The functions of these antigens will be investigated in both epidermal and lymphocyte systems in vitro. Characterization and purification of these antigens will be done by SDS-PAGE analysis and affinity chromatography. These monoclonal antibodies are being applied to localize abnormalities in keratinization that occur in diseases of altered epidermal differentiation, e.g., psoriasis. In psoriatic skin, evidence has been obtained for abnormal patterns of epidermal reactivity with our monoclonal antibodies. These abnormalities revert to the normal pattern with successful in vivo-administered therapy. These studies of psoriasis will be enlarged and extended to other diseases characterized by abnormal epidermal differentiation. Additionally, these antibodies will be used to study the effect of retinoids, which are used to treat psoriasis, pityriasis rubra pilaris and certain of the ichthyosiform dermatoses, upon in vitro keratinocyte differentiation. Finally, basal keratinocyte specific antibodies, which react with cell surface membrane antigens, will be used to purify basal epidermal keratinocytes. In vitro cultures of purified basal keratinocytes will be established and used as autologous grafts in patients with dystrophic epidermolysis bullosa and other chronic, nonhealing wounds.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
1R01AM035676-01
Application #
3154124
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1985-09-23
Project End
1988-08-31
Budget Start
1985-09-23
Budget End
1986-08-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Type
Graduate Schools
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Frey, F L; Gottlieb, A B; Levis, W R (1988) A patient with lepromatous leprosy and anticytoskeletal antibodies. J Am Acad Dermatol 18:1179-84
Carter, D M; Balin, A K; Gottlieb, A B et al. (1988) Clinical experience with crude preparations of growth factors in healing of chronic wounds in human subjects. Prog Clin Biol Res 266:303-17
Gottlieb, A B; Fu, S M; Carter, D M et al. (1987) Marked increase in the frequency of psoriatic arthritis in psoriasis patients with HLA-DR+ keratinocytes. Arthritis Rheum 30:901-7
Gottlieb, A B; Lifshitz, B; Fu, S M et al. (1986) Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques. J Exp Med 164:1013-28
Reeves, W H; Fisher, D E; Wisniewolski, R et al. (1986) Psoriasis and Raynaud's phenomenon associated with autoantibodies to U1 and U2 small nuclear ribonucleoproteins. N Engl J Med 315:105-11
Staiano-Coico, L; Higgins, P J; Darzynkiewicz, Z et al. (1986) Human keratinocyte culture. Identification and staging of epidermal cell subpopulations. J Clin Invest 77:396-404