Specific and potent inhibitors of TNF became available in the U.S. in 1998, and were demonstrated to be potentially effective for treating sciatica in experimental models beginning in 2001. Targeted anatomic administration of one of these anti-TNF agents, etanercept, a patented treatment method, has been suggested in published pilot studies to be effective for treating selected patients with chronic disc-related pain and FBSS. The scientific basis for pain relief in these patients is supported by the many current review articles. In the future new imaging methods may allow non-invasive identification of sites of neuronal inflammation, thereby enabling more accurate localization of the "pain generators" responsible for symptom production. These treatments are still experimental. If chronic pain in FBSS has a chemical component producing inflammatory pain, then prior to additional surgery it may make sense to use an anti-inflammatory approach. Often this is first attempted with non-steroidal anti-inflammatory medications, but the long-term use of Non-steroidal anti-inflammatory drugs (NSAIDS) for patients with persistent back pain is complicated by their possible cardiovascular and gastrointestinal toxicity; and NSAIDs have limited value to intervene in TNF-mediated processes. An alternative often employed is the injection of cortisone into the spine adjacent to the suspected pain generator, a technique known as "epidural steroid injection". Although this technique began more than a decade ago for FBSS, the efficacy of epidural steroid injections is now generally thought to be limited to short term pain relief in selected patients only. In addition, epidural steroid injections, in certain settings, may result in serious complications.
The mutation in the TNFSF5 gene causes there to be no recognition of CD40 by CD40 ligand, and thus the T cells do not induce Ig class switching in B cells, so there are markedly reduced levels of IgG, IgA, and IgE, but have normal or elevated levels of IgM. CD40 ligand is also required in the functional maturation of T lymphocytes and macrophages, so patients with this disorder have a variable defect in T-lymphocyte and macrophage effector function, as well as hyper IgM. Type 2
Immunodeficiency with hyper IgM type 2 is caused by a mutation in the Activation-Induced Cytidine Deaminase (AICDA) gene, which is located on the short arm of chromosome 12. The protein that is encoded by this gene is called Activation-Induced Cytidine Deaminase (AICDA) and functions as a DNA-editing deaminase that induces somatic hypermutation, class switch recombination, and immunoglobulin gene conversion in B cells. When a person is homozygous for the mutation in the AICDA gene, the protein fails to function, and thus somatic hypermutation, class switch recombination, and immunoglobulin gene conversion cannot occur, which creates an excess of IgM. Type 3
Immunodeficiency with hyper IgM type 3 is caused by a mutation in the gene that codes for CD40. As mentioned above, CD40 is expressed on the surface of B cells, and its binding to CD40 ligand on activated T cells induces Ig class switching.