Methods and compositions for detecting autoimmune disorders

A method of identifying a metric value correlated with presence and/or extent of an autoimmune disorder in a subject or sample, said method comprising:

• (a) estimating a group of probesets that is collectively associated with a pattern wherein expression of genes represented by the probesets is associated with a disease characteristic;
• (b) generating a weighting factor that weight probesets in accordance with a scale reflecting extent of match of each individual probeset to trend of the group of probesets, and calculating the correlation coefficient of each probeset's profile to the mean profile calculated;
• (c) determining a scaling factor, wherein the scaling factor is the value required to scale individual probesets to 1;
• (d) multiplying the scaling factor by the weighting factor to generate a composite factor
• (e) multiplying a normal blood sample's signatures with the composite factor, and averaging the resulting values across both probesets and samples to generate an average value, and inverting the average value to yield a global scaling factor;
• (f) multiplying each weighting factor by the global scaling factor to obtain a vector of scalar values, and multiplying the scalar values by an expression signature from a sample of interest, and averaging the resulting values to yield a single metric that is indicative of degree of gene expression associated with Type I interferons in the sample.

A method of treating a human subject having systemic lupus erythematosus (SLE), comprising:

• (a) performing a nucleic acid-based detection assay to detect mRNA expression levels of at least three genes comprising a three gene combination listed in Table 4B in cells of a blood sample from the human subject, wherein the at least three genes do not comprise OASL, IRF7 and PARP9;
• (b) determining that the cells from the human subject express the at least three genes comprising the three gene combination at a level greater than the expression level of the respective genes in cells of a blood sample from a healthy human control;
• and
• (c) administering an effective amount of an anti-interferon-alpha antibody or an anti-interferon-alpha receptor antibody to the human subject expressing the at least three genes comprising the three gene combination at a level greater than the expression level of the respective genes in cells of a blood sample from a healthy human control, thereby treating SLE in the human subject.