Autoimmune lymphoproliferative syndrome pathophysiology: Difference between revisions

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==Pathophysiology==
==Pathophysiology==
Normally, after infectious insult, the immune system down-regulates by increasing Fas expression on activated B and T [[lymphocytes]] and [[Fas-ligand]] on activated T lymphocytes.  Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell [[apoptosis]].  Patients with [[ALPS]] have a defect in this apoptotic pathway, leading to chronic non-malignant lymphoproliferation, [[autoimmune disease]], and secondary cancers.<ref name="pmid19930184">{{cite journal| author=Teachey DT, Seif AE, Grupp SA| title=Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS). | journal=Br J Haematol | year= 2010 | volume= 148 | issue= 2 | pages= 205-16 | pmid=19930184 | doi=10.1111/j.1365-2141.2009.07991.x | pmc=PMC2929682 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19930184  }} </ref> [[T cell]] activation induce FASL [[expression]] leading to binding with the FAS [[receptor]] on nearby [[cells]]. This pathway activates the FAS associated [[protein]] with death domain (FADD). FADD then create the death inducing signal complex(DISC) in association with pro-caspase 8 and pro-caspase 10. DISC activates terminal [[caspases]] and induce [[apoptosis]] which is known as activation induced [[cell death]](AICD). In ALPS , [[T cells]] become defective due to the [[mutation]] in FASL pathway. Though most of these [[mutations]] are [[autosomal dominant]], some are [[autosomal recessive]] type or sporadic [[mutations]]. Self reactive T cells are accumulated in ALPS which are negative for both [[CD4]] and [[CD8]] cells(double negative,DNT) and positive for α/β T [[cell receptor]]. DNT [[cells]] are responsible for hyperavtive [[mTOR]] oathway. Hyperactive [[mTOR]] pathway induce abnormal [[lymphoproliferation]] in [[ALPS]].<ref name="MatsonYang2019">{{cite journal|last1=Matson|first1=Daniel R.|last2=Yang|first2=David T.|title=Autoimmune Lymphoproliferative Syndrome: An Overview|journal=Archives of Pathology & Laboratory Medicine|volume=144|issue=2|year=2019|pages=245–251|issn=0003-9985|doi=10.5858/arpa.2018-0190-RS}}</ref><ref name="VölklRensing-Ehl2016">{{cite journal|last1=Völkl|first1=Simon|last2=Rensing-Ehl|first2=Anne|last3=Allgäuer|first3=Andrea|last4=Schreiner|first4=Elisabeth|last5=Lorenz|first5=Myriam Ricarda|last6=Rohr|first6=Jan|last7=Klemann|first7=Christian|last8=Fuchs|first8=Ilka|last9=Schuster|first9=Volker|last10=von Bueren|first10=André O.|last11=Naumann-Bartsch|first11=Nora|last12=Gambineri|first12=Eleonora|last13=Siepermann|first13=Kathrin|last14=Kobbe|first14=Robin|last15=Nathrath|first15=Michaela|last16=Arkwright|first16=Peter D.|last17=Miano|first17=Maurizio|last18=Stachel|first18=Klaus-Daniel|last19=Metzler|first19=Markus|last20=Schwarz|first20=Klaus|last21=Kremer|first21=Anita N.|last22=Speckmann|first22=Carsten|last23=Ehl|first23=Stephan|last24=Mackensen|first24=Andreas|title=Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome|journal=Blood|volume=128|issue=2|year=2016|pages=227–238|issn=0006-4971|doi=10.1182/blood-2015-11-685024}}</ref>
<br />
[[File:ALPS.png|center|thumb|306x306px|Activation induced cell pathway by Fast apoptosis signal (FAS) receptor.<ref name="MatsonYang2019">{{cite journal|last1=Matson|first1=Daniel R.|last2=Yang|first2=David T.|title=Autoimmune Lymphoproliferative Syndrome: An Overview|journal=Archives of Pathology & Laboratory Medicine|volume=144|issue=2|year=2019|pages=245–251|issn=0003-9985|doi=10.5858/arpa.2018-0190-RS}}</ref>]]


===Associated Conditions===
===Associated Conditions===
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**Renal: Autoimmune [[glomerulonephritis]], [[nephrotic syndrome]]
**Renal: Autoimmune [[glomerulonephritis]], [[nephrotic syndrome]]
*Cancer: Secondary neoplasms affect approximately 10% of patients.  True prevalence unknown as <20 reported cases of [[cancer]].  Most common EBER+ Non-Hodgkin's and [[Hodgkin's]] lymphoma
*Cancer: Secondary neoplasms affect approximately 10% of patients.  True prevalence unknown as <20 reported cases of [[cancer]].  Most common EBER+ Non-Hodgkin's and [[Hodgkin's]] lymphoma
==Microscopic Pathology==
[[Histopathological]] study findings can be helpful to [[diagnose]] [[Autoimmune lymphoproliferative syndrome]]. The findings are
*Paracortical expansion with infiltration of [[polyclonal]] [[TCR]] α/β+ [[DNT]] [[cells]].<ref name="LiHuang2015">{{cite journal|last1=Li|first1=Pu|last2=Huang|first2=Ping|last3=Yang|first3=Ye|last4=Hao|first4=Mu|last5=Peng|first5=Hongwei|last6=Li|first6=Fei|title=Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS)|journal=Clinical Reviews in Allergy & Immunology|volume=50|issue=1|year=2015|pages=55–63|issn=1080-0549|doi=10.1007/s12016-015-8466-y}}</ref>
*[[DNT]] [[cells]] express TIA-1 and CD57, CD45RO negative
*Follicular [[hyperplasia]]
*Polyclonal [[plasmacytosis]]
*[[Spleen]] has expanded [[T cell]] areas dominated by [[DNT]] [[cells]].
[[File:Gr3.jpg|center|thumb|Histopathology of spleen in ALPS.<ref name="LimStraus1998">{{cite journal|last1=Lim|first1=Megan S.|last2=Straus|first2=Stephen E.|last3=Dale|first3=Janet K.|last4=Fleisher|first4=Thomas A.|last5=Stetler-Stevenson|first5=Maryalice|last6=Strober|first6=Warren|last7=Sneller|first7=Michael C.|last8=Puck|first8=Jennifer M.|last9=Lenardo|first9=Michael J.|last10=Elenitoba-Johnson|first10=Kojo S.J.|last11=Lin|first11=Albert Y.|last12=Raffeld|first12=Mark|last13=Jaffe|first13=Elaine S.|title=Pathological Findings in Human Autoimmune Lymphoproliferative Syndrome|journal=The American Journal of Pathology|volume=153|issue=5|year=1998|pages=1541–1550|issn=00029440|doi=10.1016/S0002-9440(10)65742-2}}</ref>]][[File:Gr1.jpg|center|thumb|Histopathology of lymph nodes in ALPS.<ref name="LimStraus1998" />]]<br />


==References==
==References==
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Hematology]]
[[Category:Hematology]]
{{WH}}
{{WS}}

Latest revision as of 04:12, 6 August 2021

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Editor-In-Chief: David Teachey, MD [1] Sharmi Biswas, M.B.B.S

Overview

Autoimmune lymphoproliferative syndrome(ALPS) is the first disease in human beings which are caused by apoptosis defect. Defect in FAS signaling cause benign chronic lymphoproliferation followed by accumulation of TCRαβ(+) CD4(-) CD8(-) double-negative T (DNT) cells. FAS also prevent the mailgnant proliferation of lymphocytes , so ALPS patients are at higher risk of developing lymphoma.There is an identified genetic defect in 2/3 rd of the total cases of ALPS. Germline mutation is the most common type. Somatic mutation, mutations in the proteins of FAS ligand(FASL) and caspase are also responsible in some cases.The pathogenesis of ALPS is still not very clear and research is ongoing.

Pathophysiology

Associated Conditions

Microscopic Pathology

Histopathological study findings can be helpful to diagnose Autoimmune lymphoproliferative syndrome. The findings are

Histopathology of spleen in ALPS.[3]
Histopathology of lymph nodes in ALPS.[3]


References

  1. ↑ Teachey DT, Manno CS, Axsom KM, Andrews T, Choi JK, Greenbaum BH; et al. (2005). "Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS)". Blood. 105 (6): 2443–8. doi:10.1182/blood-2004-09-3542. PMID 15542578.
  2. ↑ Li, Pu; Huang, Ping; Yang, Ye; Hao, Mu; Peng, Hongwei; Li, Fei (2015). "Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS)". Clinical Reviews in Allergy & Immunology. 50 (1): 55–63. doi:10.1007/s12016-015-8466-y. ISSN 1080-0549.
  3. ↑ 3.0 3.1 Lim, Megan S.; Straus, Stephen E.; Dale, Janet K.; Fleisher, Thomas A.; Stetler-Stevenson, Maryalice; Strober, Warren; Sneller, Michael C.; Puck, Jennifer M.; Lenardo, Michael J.; Elenitoba-Johnson, Kojo S.J.; Lin, Albert Y.; Raffeld, Mark; Jaffe, Elaine S. (1998). "Pathological Findings in Human Autoimmune Lymphoproliferative Syndrome". The American Journal of Pathology. 153 (5): 1541–1550. doi:10.1016/S0002-9440(10)65742-2. ISSN 0002-9440.
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