Autoimmune lymphoproliferative syndrome: A disorder of immune dysregulation

Análisis del gen Fas como molécula causante del lupus eritematoso sistémico en pacientes con vasculitis IgA (púrpura de Henoch-Schönlein)

“…[9][10][11] SLE is a chronic immune disease that results from the formation of anti-DNA antibodies due to apoptotic clearance failure, leading to systemic inflammation in multiple tissues and systems. [10][11][12][13][14][15][16][17] A positive association between HSP and juvenile SLE was reported in a case-control study. The investigators identified particular risk factors based on information obtained from a systematic review, including childhood age of approximately 10 years, female sex, and anemia.…”

“…[12][13][14][15] The clinical manifestations of lymphoproliferative syndrome triggered by Fas malfunction encompass the existence of adenopathy, splenomegaly, and cytopenias in the pediatric population. 16 In the year 2013, research was carried out which revealed that Fas modifications led to a rise in the ratio of activation in a majority of cells where it is present; nevertheless, as mentioned earlier, it is reduced in both T lymphocytes and B lymphocytes. This implies that excessive lymphoid proliferation cannot be subjected to appropriate apoptosis and subsequent physiological clearance, leading to the perpetuation of lymphoproliferative syndrome over time and its progression into a chronic condition.…”

“…This triggers the activation of the autoimmune system and the eventual production of doublestranded anti-DNA and antinuclear antibodies. 15 a commonality in the form of the deficiency in apoptotic clearance and lymphoproliferative syndrome, 10,12,16,17 from this point forward, we will clarify that the pathophysiological stages may potentially originate from the disturbance of a unique molecular pathway related to a gene that encodes a protein, specifically Fas (cell surface death receptor), which plays an essential role in apoptotic mechanisms.…”

“…This proposed scheme offers a potential molecular relationship between HSP and systemic lupus erythematosus, but it should be noted that the downregulation of genes ENST00000378432, ENST00000571370, uc001kfc.1, and uc010qna.2 is not absolute, as alterations in p53 and TNF may also result in deregulation of Fas and apoptotic clearance. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]…”

“…[13][14][15] The apoptotic process being deficient in autoimmune diseases like SLE and HSP causes the perpetuation of the lymphoproliferative syndrome and the inability of the organism to eliminate it. [13][14][15][16][17] In the pathogenesis of systemic lupus erythematosus and IgA vasculitis there is a common pathway that is increased, the FAS/FAS ligand (FASL) pathway, however in both diseases there are mutations that interfere with its function. Fas and FasL are cell surface molecules that play an important role in apoptosis.…”