Conversely, TAM activators have been proposed as possible treatments for several autoimmune indications (Rothlin and Lemke, 2010; van den Brand et al., 2013).
Conventional methods, such as monoclonal anti-IL-17A antibodies, are currently being developed for RA and psoriasis as well as other autoimmune indications.
Rituximab is currently being evaluated in several additional autoimmune indications, with phase 3 trials ongoing in pemphigus (ClinicalTrials.gov NCT00784589), autoimmune hemolytic anemia (AIHA) (ClinicalTrials.gov NCT01181154), and immune thrombocytopenia (ITP) (ClinicalTrials.gov NCT00344149) (Table 1).
Therapeutic approaches currently pursued in the clinic are not yet geared towards targeting specific B-cell subsets, but have nonetheless already generated some very promising results in a variety of autoimmune indications.
This drug is highly effective at killing lymphocytes and is now licensed for the treatment of chronic lymphocytic leukaemia whilst continuing to be developed for a number of autoimmune indications.
While tabalumab development was discontinued following insufficient efficacy observed in phase 3 RA/systemic lupus erythematosus studies, other BAFF pathway drugs are approved for (belimumab) or being investigated in (atacicept, briobacept) other autoimmune indications, and BAFF bi-specific molecules are in development.
Monoclonal antibodies and recombinant fusion proteins that target pro-inflammatory cytokines such as TNF, IL-1, IL-6, IL-12 and IL-23 are extremely effective for some autoimmune indications (Table 1), and agents that target IL-17 are in development.
Recent studies expanding Tregs in vivo with low-dose IL-2 achieved major clinical successes highlighting the potential to optimize this pleiotropic cytokine for inflammatory and autoimmune disease indications.
For instance, certain MHC alleles have shown genetic association to diseases, so that patients with autoimmune diseases (some indications for adalimumab) may have a different distribution for MHC alleles compared to normal patients, which are simulated currently.
Our series of heterogeneous cases reported here is just an indication that autoimmune thyroiditis may be frequently observed in concurrence with bipolar spectrum disorders.
While initial studies are encouraging, its clinical development for autoimmune diseases (an alternative indication) was suspended after excess deaths due to opportunistic infections, which may cause concern in future lymphoma studies.
