A malfunctioning immune system could imply anything from a death sentence (inherited immune system disorders) to lifelong malaise (allergies, autoimmunities and chronic inflammatory disorders).
In recent decades, scientists have made giant strides in treating inherited immune system disorders.
In 1971, David Vetter – Wikipedia was the second child born to a Houston couple. His older brother suffered repeated infections and died a few months after birth, shortly after he was diagnosed as having SCID, Severe combined immunodeficiency – Wikipedia.
Back then a child born with such a severe immunodeficiency lived an unimaginably difficult life and faced imminent death. Limited treatment options were merely palliative and only extreme physical cocooning minimized risk of catching infections. Also a SCID, David was placed into a sterile plastic isolator as soon as he was delivered by C-section, and lived in permanent isolation the rest of his brief and unbelievably surreal life.
By the time he died at the age of 12 in 1984, David spent his entire life inside a plastic, germ-free chamber, never having physically touched anyone nor being touched, becoming famous as the original Bubble Boy (see below from 1). According to his mother, Carol Ann Demaret, one of David’s dreams had been to ‘walk barefoot in the grass‘ (2). Obviously, he never did.
Contrast with today when highly effective and even curative treatments such as bone marrow and hematopoietic cell transplants have transformed the lives of those born with an incurable and serious immunodeficiency such as SCID. At this point, >500 transplant centers around the world have carried out >1 million HCTs for a variety of such immune system disorders.
At the same time IVIG or Immunoglobulin therapy – Wikipedia has emerged as standard therapy for treating B cell and antibody deficiencies while gene therapy is making a comeback as a viable treatment option for many inherited immune system disorders.
Meantime scientists continue to identify new genes involved in PIDs. At the last count >120 genes and >150 PIDs (3).
A remarkable pace of progress considering even something as simple as the diagnosis of primary immunodeficiencies (PIDs) wasn’t simple and most doctors weren’t even adequately trained to do so. After all, even the cheat-sheet called ‘Ten Warning Signs of Primary Immunodeficiency‘ was only developed in the early 1990s (see below from 4).
However, there’s a long way to go with allergies, autoimmunities and chronic inflammatory disorders (e.g., inflammatory bowel disease).
Prevalence of these conditions increased dramatically in recent years, especially in older industrialized countries, even as their accurate diagnoses and treatments lag behind. For long only glucocorticoids, other immunosuppressives and non-specific painkillers were the mainstay Rx.
In recent years many biologics such as mAbs, Monoclonal antibody – Wikipedia, and small molecules that target specific enzymes and cytokines have rapidly gained regulatory approval. However, such therapies only better target symptoms and don’t address root causes even as they’re found to work optimally only in subsets of patients.
Poorly predictive animal models and poor clinical definitions are the major hurdles that prevent faster progress. For example, it’s entirely possible that diseases such as MS, Multiple sclerosis – Wikipedia, and SLE, Systemic lupus erythematosus – Wikipedia, are more accurately syndromes, the upshot being subsets of patients could differ in key disease features. In the case of most autoimmunities, even some basic questions such as the identity of target antigen(s) remain unknown.
- Not knowing the antigen(s) that are the target(s) of the autoimmune responses makes it difficult to precisely treat an autoimmune disease in such a way as to ensure minimal collateral damage.
- As for allergies and chronic inflammatory disorders, more effective treatments can only come when their underlying causes are better understood, which is not yet the case.
Bibliography
1. Chinn, Ivan K., and William T. Shearer. “Severe combined immunodeficiency disorders.” Immunology and Allergy Clinics 35.4 (2015): 671-694.
2. David’s Story. William T. Shearer, Carol Ann Demaret. Etzioni, Amos, and Hans D. Ochs, eds. Primary Immunodeficiency Disorders: A Historic and Scientific Perspective. Academic Press, 2014, pages 313-326.
3. Picard, Capucine, et al. “Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015.” Journal of clinical immunology 35.8 (2015): 696-726. Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015