The United States of America As Represented by the Department of Health

The United States of America As Represented by the Secretary of

The United States of America As Represented by the Secretary, Department

Biomira USA Inc.

Biormia USA Inc.

Paritosh Ghosh

Augusto C Ochoa

Dan L Longo

Howard A Young

Richard J Robb

Mary Neville

Methods of identifying a patient having an altered immune status involve determining an immune status index for the patient and comparing it to the immune status index in healthy individuals. In general, an immune status index is the ratio of the amount of a protein that varies significantly in a patient with an altered immune status to the amount of another protein that is substantially invariant in both healthy and immune-altered individuals. Variable proteins can be TCR subunit proteins, T lymphocyte signal transduction pathway proteins, polynucleotide binding proteins or biological response modifiers (BRM). In addition, the ratio of a TH-1-type BRM to a TH-2-type BRM, the ratio of cytoplasmic to nuclear levels of polynucleotide binding proteins, the pattern of protein binding to an oligonucleotide probe that comprises the protein binding region of a gene for a BRM, or the pattern of distribution of T lymphocytes in a density gradient following density gradient centrifugation are also suitable as an immune status index. The methods are useful in identifying patients exhibiting immunosuppression, hyperimmunity and autoimmunity, as well as in assessing the immune status of a patient undergoing organ transplant.

Methods of identifying patients having an altered immune status

A soluble immunosuppressive factor present in serum derived from tumor-bearing mammals, is associated with changes in TCR protein subunit levels, T lymphocyte signal transduction pathway proteins. These changes provide a method of determining the level of immunosuppression in a mammal by determining the level of expression of at least one selected TCR subunit protein, a protein in the T lymphocyte signal transduction pathway, or of the NF-.kappa.B/rel family and comparing the level and pattern to that found in non-immunosuppressed individuals. The method is useful to identify patients having T lymphocytes capable of activation for immunotherapy and for identifying agents which cause or reverse immunosuppression. An isolated immunosuppressive factor associated with the level of expression of the proteins is useful for suppressing the immune response, for example, in organ transplantation.

Evaluation and treatment of patients with progressive immunosuppression

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Frederick, MD, United States of America

Paritosh Ghosh