Thesis (Ph.D)-Cairo University, 2023.

Bibliography: pages 107-130.

LP is a chronic skin disease whose exact pathogenesis is still unclear. The mechanisms involved in the pathogenesis of the disease are not fully elucidated. Several theories that could explain the appearance of LP lesions have been postulated. It remains a major burden on the affected patients due to it is impact on their quality of life.
The immunological tolerance develops through immunological checkpoints such as cytotoxic T-lymphocyte antigen 4 and programmed death ligand/receptor, which lead to functional lymphocyte inactivation (anergy). Several types of immune checkpoint-directed antibodies targeting PD-1 or its ligand have been approved for various cancer therapies and become a promising therapeutic approach in treating tumors.
Many dermatological adverse effects have been reported after using the patients receiving anti-PD-1/PD-L1 therapy including the lichenoid dermatosis which affects around 17% of patients, this suggests that weak expression of PD-1 and PD-L1 in LP might have causative role in the pathogenesis of the disease, raising the possibility of a role for PD-1/PD-L1 checkpoint in LP pathogenesis.
The expression of PD-1 protein has been assessed in different systemic and cutaneous diseases, including psoriasis and vitiligo which have differences regarding how they stimulate the immune system in comparison to LP, although they have much similarities in the immunopathogenesis processes.
In the current study, patients were recruited from the dermatology outpatient clinic, Kasr Al Aini, Faculty of Medicine, Cairo University. The study was conducted on 30 patients with LP and 30 healthy controls. A 3 mm punch biopsy was taken from lesional and nonlesional skin of the patients

and one biopsy from the healthy controls, the levels of PD-1/PD-L1 were assessed by ELISA.
We found that PD-1 levels in lesional skin were significantly lower than in both nonlesional skin and healthy controls. Also, PD-L1 levels in lesional skin were significantly lower than in both nonlesional skin and healthy controls. Also, PD-1 and PD-L1 levels in nonlesional skin were significantly lower than in healthy controls. There was statistically significant positive correlation between PD-1 and PD-L1 in lesional and nonlesional skin. There was statistically significant positive correlation between lesional PD-1 and nonlesional PD-1. In addition, there was statistically significant positive correlation between lesional PD-L1 and nonlesional PD-L1.
The results imply that PD-1/PD-L1 may be involved in the pathogenesis of LP.
In conclusion, it is suggested that PD-1 and PD-L1 might have a role in LP pathogenesis. Thus, there may be a therapeutic implication for PD-1 agonists in LP and other autoimmune diseases that will need wider scale studies before clinical implementation.

اﻟﺤﺰاز اﻟﻤﺴﻄﺢ ھﻮ ﻣﺮض ﺟﻠﺪي ﻣﺰﻣﻦ ﻻ ﺗﺰال أﺳﺒﺎﺑﮫ اﻟﻤﺮﺿﯿﺔ ﻏﯿﺮ واﺿﺤﺔ. ﻟﻢ ﯾﺘﻢ ﺗﻮﺿﯿﺢ اﻵﻟﯿﺎت اﻟﻤﺸﺎرﻛﺔ ﻓﻲ اﻟﺘﺴﺒﺐ ﻓﻲ اﻟﻤﺮض ﺑﺸﻜﻞ ﻛﺎﻣﻞ. ﺗﻢ اﻓﺘﺮاض اﻟﻌﺪﯾﺪ ﻣﻦ اﻟﻨﻈﺮﯾﺎت اﻟﺘﻲ ﯾﻤﻜﻦ أن ﺗﻔﺴﺮ ظﮭﻮر ﻣﺮض اﻟﺤﺰاز اﻟﻤﺴﻄﺢ. اﻟﺤﺰاز اﻟﻤﺴﻄﺢ ﻻ ﯾﺰال ﯾﻤﺜﻞ ﻋﺒﺌًﺎ ﻛﺒﯿﺮا ﻋﻠﻰ اﻟﻤﺮﺿﻰ اﻟﻤﺼﺎﺑﯿﻦ ﺑﺴﺒﺐ ﺗﺄﺛﯿﺮه ﻋﻠﻰ ﻧﻮﻋﯿﺔ ﺣﯿﺎﺗﮭﻢ. ﯾﺘﻄﻮر اﻟﺘﺤﻤﻞ اﻟﻤﻨﺎﻋﻲ ﻣﻦ ﺧﻼل ﻧﻘﺎط اﻟﺘﻔﺘﯿﺶ اﻟﻤﻨﺎﻋﯿﺔ ﻣﺜﻞ ﻣﺴﺘﻀﺪ اﻟﺨﻼﯾﺎ اﻟﻠﻤﻔﺎوﯾﺔ اﻟﺘﺎﺋﯿﺔ 4 اﻟﺴﺎم ﻟﻠﺨﻼﯾﺎ وراﺑﻂ / ﻣﺴﺘﻘﺒﻞ اﻟﻤﻮت اﻟﻤﺒﺮﻣﺞ ، ﻣﻤﺎ ﯾﺆدي إﻟﻰ ﺗﺜﺒﯿﻂ اﻟﺨﻼﯾﺎ اﻟﻠﻤﻔﺎوﯾﺔ اﻟﻮظﯿﻔﯿﺔ )اﻟﺤﺴﺎﺳﯿﺔ.( ﺗﻤﺖ اﻟﻤﻮاﻓﻘﺔ ﻋﻠﻰ ﻋﺪة أﻧﻮاع ﻣﻦ اﻷﺟﺴﺎم اﻟﻤﻀﺎدة اﻟﻤﻮﺟﮭﺔ ﻟﻨﻘﺎط اﻟﺘﻔﺘﯿﺶ اﻟﻤﻨﺎﻋﯿﺔ اﻟﺘﻲ ﺗﺴﺘﮭﺪف ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ1- PD-1) ( اوﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ ﻟﻌﻼﺟﺎت اﻟﺴﺮطﺎن اﻟﻤﺨﺘﻠﻔﺔ وأﺻﺒﺤﺖ طﺮﯾﻘﺔ ﻋﻼﺟﯿﺔ واﻋﺪة ﻓﻲ ﻋﻼج اﻷورام. ﺗﻢ اﻹﺑﻼغ ﻋﻦ اﻟﻌﺪﯾﺪ ﻣﻦ اﻵﺛﺎر اﻟﻀﺎرة اﻟﺠﻠﺪﯾﺔ ﺑﻌﺪ اﺳﺘﺨﺪام اﻟﻤﺮﺿﻰ اﻟﺬﯾﻦ ﯾﺘﻠﻘﻮن اﻟﻌﻼج اﻟﻤﻀﺎد ﻟـ ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ اوﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ ﺑﻤﺎ ﻓﻲ ذﻟﻚ اﻟﺘﮭﺎب اﻟﺠﻠﺪ اﻟﺤﺰازي اﻟﺬي ﯾﺼﯿﺐ ﺣﻮاﻟﻲ 17 ٪ ﻣﻦ اﻟﻤﺮﺿﻰ ، وھﺬا ﯾﺸﯿﺮ إﻟﻰ أن اﻟﺘﻌﺒﯿﺮ اﻟﻀﻌﯿﻒ ﻋﻦ ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ اوﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ ﻓﻲ اﻟﺤﺰاز اﻟﻤﺴﻄﺢ ﻗﺪ ﺑﻜﻮن ﻟﮫ دور ﻓﻲ اﻟﺘﺴﺒﺐ ﻓﻲ اﻟﻤﺮض ، ﻣﻤﺎ ﯾﺰﯾﺪ ﻣﻦ اﺣﺘﻤﺎل دورﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ اوﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ ﻓﻲ
اﻟﺘﺴﺒﺐ ﻓﻲ ﻣﺮض اﻟﺤﺰاز اﻟﻤﺴﻄﺢ .
ﺗﻢ ﺗﻘﯿﯿﻢ اﻟﺘﻌﺒﯿﺮ ﻋﻦ ﺑﺮوﺗﯿﻦ ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ1- PD-1) ( ﻓﻲ أﻣﺮاض ﺟﮭﺎزﯾﺔ وﺟﻠﺪﯾﺔ ﻣﺨﺘﻠﻔﺔ ، ﺑﻤﺎ ﻓﻲ ذﻟﻚ اﻟﺼﺪﻓﯿﺔ واﻟﺒﮭﺎق واﻟﺘﻲ ﻟﮭﺎ اﺧﺘﻼﻓﺎت ﻓﯿﻤﺎ ﯾﺘﻌﻠﻖ ﺑﻜﯿﻔﯿﺔ ﺗﺤﻔﯿﺰ اﻟﺠﮭﺎز اﻟﻤﻨﺎﻋﻲ ﻣﻘﺎرﻧﺔً ﺑـﺎﻟﺤﺰاز
اﻟﻤﺴﻄﺢ ، ﻋﻠﻰ اﻟﺮﻏﻢ ﻣﻦ وﺟﻮد أوﺟﮫ ﺗﺸﺎﺑﮫ ﻛﺒﯿﺮة ﺑﯿﻨﮭﻤﺎ ﻓﻲ ﻋﻤﻠﯿﺎت اﻟﺘﻜ ﱡﻮن اﻟﻤﻨﺎﻋﻲ.
ﻓﻲ اﻟﺪراﺳﺔ اﻟﺤﺎﻟﯿﺔ ، ﺗﻢ ﺗﺠﻨﯿﺪ اﻟﻤﺮﺿﻰ ﻣﻦ اﻟﻌﯿﺎدة اﻟﺨﺎرﺟﯿﺔ ﻟﻸﻣﺮاض اﻟﺠﻠﺪﯾﺔ ، ﻗﺼﺮ اﻟﻌﯿﻨﻲ ، ﻛﻠﯿﺔ اﻟﻄﺐ
، ﺟﺎﻣﻌﺔ اﻟﻘﺎھﺮة. أﺟﺮﯾﺖ اﻟﺪراﺳﺔ ﻋﻠﻰ 30 ﻣﺮﯾﻀﺎ ﯾﻌﺎﻧﻮن ﻣﻦ اﻟﺤﺰاز اﻟﻤﺴﻄﺢ و 30 ﺷﺎھﺪ. ﺗﻢ أﺧﺬ ﺧﺰﻋﺔ
3 ﻣﻢ ﻣﻦ اﻟﺠﻠﺪ اﻟﻤﺼﺎب وﻏﯿﺮ اﻟﻤﺼﺎب ﻟﻠﻤﺮﺿﻰ وﺧﺰﻋﺔ واﺣﺪة ﻣﻦ اﺟﻠﺪ اﻟﺸﻮاھﺪ ، ﺗﻢ ﺗﻘﯿﯿﻢ ﻣﺴﺘﻮﯾﺎت ﻋﺎﻣﻞ
ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ1- PD-1) ( اوﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ1- ) PD-L1 ( ﺑﻮاﺳﻄﺔ ﺗﻘﻨﯿﺔ .ELISA
(PD-1) أﻗﻞ اﺣﺼﺎﺋﯿﺎً ﻓﻲ اﻟﺠﻠﺪ اﻟﻤﺼﺎب ﺑﺎﻟﺤﺰاز ﻣﻘﺎرﻧﺔ
أظﮭﺮت ﻧﺘﺎﺋﺠﻨﺎ أن ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ 1-
ﺑﺎﻟﺠﻠﺪ ﻏﯿﺮ اﻟﻤﺼﺎب ﻟﻠﻤﺮﺿﻰ واﻟﺸﻮاھﺪ، وﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ- 1 (PD-L1) أﻗﻞ اﺣﺼﺎﺋﯿﺎً ﻓﻲ اﻟﺠﻠﺪ اﻟﻤﺼﺎب ﺑﺎﻟﺤﺰاز ﻟﻠﻤﺮﺿﻰ ﻣﻘﺎرﻧﺔ ﺑﺎﻟﺠﻠﺪ ﻏﯿﺮ اﻟﻤﺼﺎب واﻟﺸﻮاھﺪ. وﻛﺬﻟﻚ اﺗﻀﺢ أن ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ
وﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ- 1 PD-L1) ( أﻗﻞ اﺣﺼﺎﺋﯿﺎً ﻓﻲ اﻟﺠﻠﺪ ﻏﯿﺮ ﻣﺼﺎب
اﻟﻤﺒﺮﻣﺞ 1- (PD-1)
ﻟﻠﻤﺮﺿﻰ ﻣﻘﺎرﻧﺔ ﺑﺠﻠﺪ اﻟﺸﻮاھﺪ ، اظﮭﺮت اﻟﻨﺘﺎﺋﺞ ارﺗﺒﺎط اﯾﺠﺎﺑﻲ ذو دﻻﻟﮫ اﺣﺼﺎﺋﯿﮫ ﺑﯿﻦ ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ
اﻟﻤﺒﺮﻣﺞ1 (PD-1) وﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ1 (PD-L1) ﻓﻲ اﻟﺠﻠﺪ اﻟﻤﺼﺎب ﺑﺎﻟﺤﺰاز ﻟﻠﻤﺮﺿﻰ و اﻟﺠﻠﺪ
ﻏﯿﺮ اﻟﻤﺼﺎب، اظﮭﺮت اﻟﻨﺘﺎﺋﺞ ارﺗﺒﺎط اﯾﺠﺎﺑﻲ ذو دﻻﻟﮫ اﺣﺼﺎﺋﯿﮫ ﺑﯿﻦ ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ(PD-1- 1 ﻓﻲ اﻟﺠﻠﺪ اﻟﻤﺼﺎب ﺑﺎﻟﺤﺰاز ﻟﻠﻤﺮﺿﻰ و اﻟﺠﻠﺪ ﻏﯿﺮ اﻟﻤﺼﺎب وﻛﺬﻟﻚ اظﮭﺮت اﻟﻨﺘﺎﺋﺞ ارﺗﺒﺎط اﯾﺠﺎﺑﻲ ذو دﻻﻟﮫ اﺣﺼﺎﺋﯿﮫ ﺑﯿﻦ ﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ- 1 PD-L1) ( ﻓﻲ اﻟﺠﻠﺪ اﻟﻤﺼﺎب ﺑﺎﻟﺤﺰاز ﻟﻠﻤﺮﺿﻰ و اﻟﺠﻠﺪ
ﻏﯿﺮ اﻟﻤﺼﺎب.
ﺗﺸﯿﺮ اﻟﻨﺘﺎﺋﺞ إﻟﻰ أن ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ1- PD-1) ( اوﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ - 1 (PD-L1)
ﻗﺪ ﯾﻜﻮن ﻣﺘﻮرطﺎ ﻓﻲ اﻟﺘﺴﺒﺐ ﻓﻲ اﻟﺤﺰاز اﻟﻤﺴﻄﺢ.
ﻓﻲ اﻟﺨﺘﺎم ، ُﯾﻘﺘﺮح أن ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ1- PD-1) ( اوﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ - (PD-1
L1) ﻗﺪ ﯾﻜﻮن ﻟﮭﻤﺎ دور ﻓﻲ اﻟﺘﺴﺒﺐ ﻓﻲ اﻟﺤﺰاز اﻟﻤﺴﻄﺢ. وﺑﺎﻟﺘﺎﻟﻲ ، ﻗﺪ ﯾﻜﻮن ھﻨﺎك ﺗﺄﺛﯿﺮ ﻋﻼﺟﻲ ﻟﻤﻨﺒﮭﺎت
وأﻣﺮاض اﻟﻤﻨﺎﻋﺔ اﻟﺬاﺗﯿﺔ اﻷﺧﺮى اﻟﺘﻲ

ﻓﻲ اﻟﺤﺰاز اﻟﻤﺴﻄﺢ

ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ1- PD-1) (

ﺳﺘﺤﺘﺎج إﻟﻰ دراﺳﺎت ﻋﻠﻰ ﻧﻄﺎق أوﺳﻊ ﻗﺒﻞ اﻟﺘﻨﻔﯿﺬ اﻟﺴﺮﯾﺮي.

وﻟﺠﯿﻦ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ - 1 (PD-

ﻓﺄن اﺧﺘﻼل ﻋﻤﻞ ﻋﺎﻣﻞ ﻣﻮت اﻟﺨﻠﯿﺔ اﻟﻤﺒﺮﻣﺞ 1- (PD-1)

وﻋﻠﯿﮫ

L1) ﻗﺪ ﯾﻜﻮن ﻟﮭﻤﺎ دوراً ھﺎﻣﺎً ﻓﻲ ﺗﻜﻮن اﻟﺤﺰاز اﻟﻤﺴﻄﺢ.وﻻن ﻟﮭﻤﺎ دور ﻣﮭﻢ ﻣﻦ اﻟﻤﻤﻜﻦ اﺳﺘﺨﺪاﻣﮭﺎ ﻛﻮﺳﯿﻠﮫ
ﻟﻌﻼج اﻟﺤﺰاز اﻟﻤﺴﻄﺢ واﻻﻣﺮاض اﻟﻤﻨﺎﻋﯿﮫ اﻻﺧﺮى وﻟﻜﻦ ﺗﺤﺘﺎج اﻟﻰ ﺗﺠﺎرب ﺳﺮﯾﺮﯾﮫ اﻛﺒﺮ ﻗﺒﻞ ﺗﻄﺒﯿﻘﮭﺎ
ﻋﻤﻠﯿﺎ.

Issued also as CD

Text in English and abstract in Arabic & English.