Lupus Is A Chronic Autoimmune Disease. It Can Cause Inflammation Of Joints And Organs, Affect Exercise And Skin, And Lead To Fatigue. In Extreme Cases, Symptoms Can Even Make People Weak, And The Consequences Can Be Fatal. At Present, There Is No Cure For The Disease, And About 50000 People Are Affected In The UK.
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The Existing Treatment Methods Are Mainly Immunosuppressants, Whose Function Is To Suppress The Immune System To Improve Symptoms.
In A Study Published In Nature On April 27 Local Time, Scientists Sequenced The Whole Genome Of The DNA Of A Spanish Child Named Gabriela, Who Was Diagnosed With Severe Lupus At The Age Of 7. Such A Severe Case Of Early Onset Is Rare And Indicates A Single Genetic Cause.
In A Genetic Analysis Conducted By The Center For Personalized Immunology At The Australian National University, Researchers Found A Single Point Mutation In The TLR7 Gene. Through Referrals From The China Australia Personalized Immunology Center (cacpi) Of Renji Hospital In The United States And Shanghai, They Found Other Cases Of Severe Lupus, And The Genes Of These Cases Were Also Mutated.
To Confirm That The Mutation Caused Lupus, The Team Introduced It Into Mice Using CRISPR Gene Editing Technology. The Reason Why TLR7 Mutations Continue To Develop Is That TLR7 Mice Show Similar Symptoms. The Mouse Model And Mutation Are Named "Kika", And Gabriela Is The Core Of This Discovery.
Carola Vinuesa, Senior Author And Principal Researcher Of The Paper From The Australian Center For Personalized Immunology, Is The Co Director Of Cacpi And Now The Team Leader Of Crick University, "Finding An Effective Treatment For Lupus Has Always Been A Huge Challenge. The Immunosuppressants Currently Used May Have Serious Side Effects, Which Makes Patients More Vulnerable To Infection. In The Past 60 Years Or So, The FDA Has Only Approved A New Treatment. This Is The First Time To Prove That TLR7 Mutation Can Lead To Lupus, Which Provides Clear Evidence For A Way Of Producing This Disease," She Said
Professor Nan Shen, CO Director Of The Cacpi Paper, Added: "although Only A Few Lupus Patients May Have Mutations In TLR7 Itself, We Do Know That Many Patients Have Signs Of TLR7 Pathway Hyperactivity. By Identifying The Causal Relationship Between Gene Mutations And Disease, We Can Start Looking For More Effective Treatments."
The Mutations Found By The Researchers Made The TLR7 Protein More Likely To Bind To A Nucleic Acid Component Called Guanosine And Become More Active. This Increases The Sensitivity Of Immune Cells, Which Makes Them More Likely To Mistakenly Recognize And Attack Healthy Tissues As Foreign Or Damaged Tissues.
Interestingly, Other Studies Have Shown That Mutations That Make TLR7 Less Active Are Associated With Some Cases Of Severe Covid-19 Infection, Highlighting The Delicate Balance Of The Healthy Immune System.
This Work May Also Help Explain Why The Incidence Rate Of Lupus In Women Is About 10 Times Higher Than That In Men. Because TLR7 Is Located On The X Chromosome, Women Have Two Copies Of The Gene And Men Have One. Usually, One X Chromosome In Women Is Inactive, But In This Part Of The Chromosome, The Silence Of The Second Copy Is Often Incomplete. This Means That Women With Mutations In The Gene Can Have Two Valid Copies.
Dr Carmen De Lucas Collantes, Co-author Of The Study, Said That The Identification Of TLR7 As The Cause Of Lupus In This Extremely Serious Case Has Brought Hope For More Targeted Therapies For Gabriela And Other Lupus Patients Who May Benefit From This Finding.
Gabriela, Who Is Now A Teenager And Keeps In Touch With The Research Team, Said: "I Hope This Discovery Will Bring Hope To Patients With Lupus Erythematosus And Make Them Feel That They Are Not Fighting Alone. I Hope This Research Can Continue And Eventually Form A Specific Treatment To Benefit So Many Lupus Soldiers With This Disease."
Researchers Are Now Working With Pharmaceutical Companies To Explore The Development Or Reuse Of Existing Treatments That Target The TLR7 Gene. In Addition, They Hope That The Treatment Of This Gene Can Also Help Patients With Related Diseases.
Carola Added: "there Are Other Systemic Autoimmune Diseases, Such As Rheumatoid Arthritis And Dermatomyositis, Which Belong To The Same Broad Family As Lupus. TLR7 May Also Play A Role In These Diseases."
Further Research On The Downstream Pathogenesis Of Tl7 Has Begun With The Discovery Of A Key Mutation In The Laboratory Of Crick.