The Primary Lesion Theory of Autoimmunity: A Speculative Hypothesis

Abstract

Autoaggression and autoimmune attack are established vernacular in the literature of autoimmune disease, and reflect the popular view that autoimmunity is a disease of immune dysregulation in which the immune system inappropriately attacks healthy tissues. The aim of this article is to focus attention on an alternative, indeed opposite, view--that autoimmunity represents the response to a primary lesion in the target tissue, rather than its cause, and that like alloimmunity, autoimmunity is physiological appropriate and protective. The cell death and tissue damage which results is characteristic of an immune response programmed to eliminate immunogen, remove detritus and isolate the lesion.

Celiac Disease-Associated Autoimmune Endocrinopathies

“…There have been many studies performed to determine the incidence of CD coexisting with diabetes (12,13,16,21,29,34,35,43,44,47,48,51,53,59,61,62,66,68,71,78,80,81,83,100,106,112,113,114,116). An incidence of 2 to 8.5% has been reported, depending upon the diagnostic criteria used for CD.…”

Pathogenesis of Graves' Disease: Molecular Analysis of Anti-Thyrotropin Receptor Antibodies.

“…Theories of autoimmunity fall into four main categories: primary immune dysregulation, failure of idiotype control, molecular mimicry, and primary lesion theory [17]. Some combine two of these, and they almost certainly overlap.…”

“…Some combine two of these, and they almost certainly overlap. In the primary lesion theory, it has been hypothesized that a change in an antigen may trigger a response in a normal immune system [17], or that a proportion of the population carries a slightly altered form of an antigen which, when combined with other genetic and environmental factors, may result in the disease phenotype [18]. TSHR is an autoantigen found in many autoimmune thyroid diseases (AITD) patients, and an association has already been observed between a point mutation of TSHR and AITD susceptibility.…”

Аутоиммунный синдром перекреста (overlap-синдром) при заболеваниях щитовидной железы — ​Terra incognita тиреоидологии

“…Аутоиммунные заболевания ЩЖ представляют со-бой группу аутоиммунных тиреопатий, патогенетиче-скую основу которых составляет генетически обуслов-ленный дефект иммунной толерантности в отношении антигенов ЩЖ [1,37]. С одной стороны, антигенная структура ЩЖ включает более 10 специфических ан-тигенов, в то время как антигенный полиморфизм яв-ляется фактором аутосенсибилизации и аутоагрессии.…”

“…Имеется ряд описаний монозиготных близнецов, один из которых страда-ет ДТЗ, а другой -АИТ. Более того, оба процесса могут развиваться в одной и той же железе [13,37]. Клинические проявления в таких случаях зависят от преобладания того или иного из этих процессов.…”