METHODS AND COMPOSITIONS FOR SYSTEMIC LUPUS ERYTHEMATOSUS
The invention provides methods and compositions for the diagnosis, prognosis, and/or treatment response characterization of individuals suffering from systemic lupus erythematosus (SLE) using single cell network profiling.
1 . A method of determining the status of an individual diagnosed with or suspected of having SLE comprising
(i) determining the activation level of an activatable element in a cell from a sample from the individual; and
(ii) based on the level determined in (i), determining the status of the individual.
2 . The method of claim 1 wherein the individual has been diagnosed with SLE and the status is current status of the disease, likelihood of a future status of the disease, or likelihood of response to treatment.
3 . The method of claim 1 wherein the cell is treated with a modulator.
4 . The method of claim 3 wherein the modulator is selected from the group consisting of CD40L, CpG-C, Anti-IgD, IL-1β, LPS, Pam3CSK4, PMA, R848, IFNα, IFNγ, IL-2, IL-4, IL-6, IL-7, IL-10, IL-15, IL-21, IL-27, and GMCSF.
5 . The method of claim 1 wherein the activatable element is selected from the group consisting of p-Akt, p-CREB, p-Erk, IkB, p-c-Jun, p-P38, p-S6, p-Stat3, p-Stat1, p-Stat3, p-Stat5, and p-Stat6.
6 . The method of claim 1 wherein the cell is a T cell, a B cell, or a monocyte, or a subset selected from the group in the TABLE.
7 . The method of claim 1 wherein the activation level of two activatable elements is determined and the determination of the status comprises finding a ratio of the levels of the two activatable elements.
8 . The method of claim 7 wherein the cells is treated with a modulator.
9 . A method of screening an agent for potential use as a therapeutic agent in SLE, comprising exposing cells to the agent and determining the activation level of one or more activatable elements single cells, and determining the suitability of the agent for potential use as a therapeutic agent based on the activation level determined.
10 . The method of claim 9 wherein the single cells are treated with a modulator.
11 . The method of claim 9 wherein the modulator is selected from the group consisting of CD40L, CpG-C, Anti-IgD, IL-1β, LPS, Pam3CSK4, PMA, R848, IFNα, IFNγ, IL-2, IL-4, IL-6, IL-7, IL-10, IL-15, IL-21, IL-27, and GMCSF.
12 . The method of claim 9 wherein the activatable element is selected from the group consisting of p-Akt, p-CREB, p-Erk, IkB, p-c-Jun, p-P38, p-S6, p-Stat3, p-Stat1, p-Stat3, p-Stat5, and p-Stat6.
13 . The method of claim 9 wherein the cell in which the activation level of the activatable element is determined is a T cell, a B cell, or a monocyte, or a subset selected from the group in the TABLE.
14 . The method of claim 9 wherein the activation level of two activatable elements is determined and the determination of the suitability of the agent comprises finding a ratio of the levels of the two activatable elements.
15 . The method of claim 9 wherein the cells is treated with a modulator.