BCR and rheumatoid arthritis: Our initial findings strongly support the prospective use of ITSI as a clinically relevant diagnostic measure of the humoral immunity/B cell component in RA, particularly in light of the recent evidence suggesting that peripherally induced immune tolerance in response to the chronic autoantigen stimulation is present in a major fraction of human naive B cells, and the scale of this tolerogenic mechanism is unique to B cells, and that peripheral tolerogenic mechanisms of selective BCR signaling inhibition are compromised in the onset of autoimmunity [28], [30], [31].