Autoinflammation and Autoimmunity: More to What Meets the Eye
I was reading today an interesting article from the Indian Journal of Rheumatology. It states that "Autoimmune and autoinflammatory disorders are both characterized by excessive undue activation of the immune system with autoimmune disorders primarily involving the adaptive immune arm of the immune system, whereas a dysregulated innate immune response is predominantly observed in autoinflammatory diseases." We know that it takes a long time to be diagnosed with SLE based on the fact that it mimics so many other illnesses, so the physicians must rule out everything else before a concrete diagnosis is confirmed.
We know that Lupus (SLE) is an autoimmune inflammatory illness which effects all the major organs of the body. The article further explains that "Among autoinflammatory diseases, the most intriguing of all is the multisystem inflammatory syndrome – children/adults. Although it shares some clinical features with Kawasaki disease, it has more gastrointestinal and systemic features. Mechanistically, it is driven by IL-10 and tumor necrosis factor-alpha with a possible role of multiple autoantibodies again making it difficult to classify. The pathogenetic mechanisms of these are unclear. They are determined by factors such as age (with MIS-C being more common in children) and gender (myositis, arthritis, GBS, myelitis, and glomerulonephritis are reported mainly in men, whereas thyroiditis and pancreatitis occur more frequently in women)."
There also exists a third dimension which states "Many autoinflammatory syndromes such as deficiency of adenosine deaminase 2, LUBAC deficiency, and APLAID as well as autoimmune diseases such as CTLA4 haploinsufficiency, CVID, and RAG1/2 deficiency are associated with concurrent immune deficiency. The updated classification of inborn errors of immunity has defined a separate subgroup for those with inherent susceptibility to autoimmunity as well as autoinflammation. These include autoimmune lymphoproliferative syndrome that presents with autoimmune cytopenias, autoimmune polyendocrine syndrome with antibodies to IL-17 resulting in immune deficiency, syndromes causing very early-onset IBD (IPEX), IL-10 deficiency, IL-10 R deficiency, etc., and those with general autoimmunity (CTLA4 and LRBA defects). Further, there is a higher prevalence of immunodeficiencies involving complement components and B-cells in adult-onset autoimmune diseases like SLE in certain ethnicities like Persians due to the high rate of consanguineous marriages. This aspect holds translational value with regard to therapeutics and may need replacement of complement components using fresh frozen plasma, IVIG, or avoidance of B-cell depleting therapy for B-cell immunodeficiency. Low copy numbers of C4A in SLE a study from Mexico have also been linked to a greater risk of infections. Some inborn errors immunity form an important third dimension in addition to autoimmunity and autoinflammation that helps us define the positions of various diseases better along the continuum."
Thus, in diseases other than monogenic diseases, innate and adaptive immune responses act in conjunction along a continuum, and not in mutual exclusion. This can be compared to the gene–environment continuum of characteristics of the human body, wherein some aspects like blood group are determined by a single set of genes, whereas skin complexion and eye color display a polygenic inheritance with environmental influence. A classification continuum based on these principles, representative of the underlying disease pathophysiology, would help classify many diseases in future.
I can only hope that one day a cure will be found, and those of us with autoinflammatory illness will not have to suffer any longer. It still remains a mystery.
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