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Wednesday, January 25, 2012

HLA and autoimmune disease association : a quick summary

Celiac disease :
  • CELIAC1 : heterodimers "DQ2" (DQA1*05-DQB1*02) or "DQ8" (DQA1*03-DQB1*03:02). Gradient of RR : DQB1*02/*02 or DQB1*02/*0302 > DQ2 > DQ8 > DQB1*02 (DQA1*05 negativo) >> DQ2/DQ8/DQB1*02 negative
  • DQ2/DQ8/DQB1*02 found in 30% of population => poor positive predictive value (1/30), very high negative predictive value
  • other predisposing genes : CELIAC2, CELIAC3/CTLA4, CELIAC4/MYO9B
  • the risks of celiac disease autoimmunity and celiac disease by the age of 5 years were 11% and 3%, respectively, among children with a single DR3–DQ2 haplotype, and 26% and 11%, respectively, among those with two copies (DR3–DQ2 homozygosity). In the adjusted model, the hazard ratios for celiac disease autoimmunity were 2.09 (95% confidence interval [CI], 1.70 to 2.56) among heterozygotes and 5.70 (95% CI, 4.66 to 6.97) among homozygotes, as compared with children who had the lowest-risk genotypes (DR4–DQ8 heterozygotes or homozygotes). Residence in Sweden was also independently associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.90; 95% CI, 1.61 to 2.25) (ref)
Type 1 diabetes mellitus :
  • haplotypes DRB1*03:01-DQA1*05:01-DQB1*02:01 or DRB1*04:01-DQA1*03:01-DQB1*03:02
  • RR in double heterozygotes = 20-40 > DR3 homozygotes  or DR4 homozygotes
  • odds ratio (OR) according to "diplotypes" (i.e. combinations of haplotypes) :

  • non DR-DQ HLA alleles predispose (A*24, B*39, B*18) or protect (B*27, A*01, A*11, A*31) (typing not recommended)
  • other genes : INS/IDDM2 VNTR, PTPN22/Lyp, CTLA4, IL2RA, IFIH1, CLEC16A, PTPN2, CYP27B1
Rheumatoid arthritis  :
  • prevalence = 0.5-1% worldwide (commonest autoimmune disease); M:F ratio 1:3
  • position 70-74 in HVR3 of HLA-DRB1 alleles : predisposing shared epitope (*01:01, *01:02, *04:01, *10:01, *14:02)) or   protective (*01:03, *04:02, *11:02, *11:03, *13:01, *13:02)
  • DRB1*03 correlates with lack of anti-CCP autoAb
  • other predisposing genes :  PTPN22/Lyp C1858T,  CTLA4, PADI4, MIF, TRAF1-C5, 6q23
Juvenile idiopathic arthritis (JIA) :
  • A*02 predisposes to early-onset JIA
  • B27 predisposes to enthesitis-associated JIA
  • DRB1*01, *08, *11, *13, DPB1*02 and DQB1*04 predispose to oliogoarticular JIA, while DRB1*04 and *07 protect from it
  • DRB1*08 and DPB1*03 predispose to polyarticular RF-negative JIA
  • DRB1*04, DQA1*03 and  DQB1*03 predispose to polyarticular RF-positive JIA
  • DRB1*01 and DQA1*0101 predispose to psoriatic JIA
  • non-HLA genes : TNFA-857A/G, MIF, SLC11A1, PTPN22
Ankylosing spondylitis / Bechterew disease and reactive arthritis :
  • all B27 alleles other than *27:06 (Sardinia) and *27:09 (South-East Asia) (OR > 100; PPV : 5%), B60 (OR 3.6), and DRB1*01
  • non-HLA genes : IL-1 family, CYP2D6, CARD15/NOD2, ANKH, ARTS1 and IL23R.
Uveitis :
  • acute anterior uveitis : B27 (expecially HLA-B*2705)
  • Behçet disease : B51
  • birdshot-like chorioretinopathy : A29 (RR = 50-250)
  • glaucomacyclitic crisis (Posner-Schlossman syndrome) : B54
  • pars-planitis : DR15
  • juvenile arthritis-related uveitis : DPB1*0202
  • tubulointerstitial nephritis and uveitis : DRB1*01:02 and DQA1*01
  • Vogt-Koyanagi-Harada syndrome : DR1 and DR4 in Caucasians and DRB1*04:05 in Asia
Behçet disease : B*510101 (RR = 6-10)
Multiple sclerosis :
  • "HLA-DR15" haplotype :
  1. DRB1*15:01, DRB5*01:01, DQA1*01:02, DQB1*06:02) and B18 (OR 2.6 or OR 6.2)
  2. DRB1*03:01 (OR = 1.4)
  • HLA-A*02:01; B*44:02; C*05:01 is a protective haplotype (OR : 0.2)
Myasthenia gravis : B8, B7, DR3 in Caucasians
  • DR9, DR13, DQ3, B12 and A10 in Japanese
  • HLA-DRB1*16,-DRB1*14 and -DQB1*05 with MuSK-MG (ref)
  • HLA A1-B8-DR3 haplotype in female patients with thymus hyperplasia and early onset MG, while HLA B7-DR2 haplotype was found in late onset MG (ref1, ref2). HLA-DQB polymorphism has also been linked to MG in earlier studies (ref). More recently, associations betweenHLA-DRB1*14, HLA-DRB1*16 and DQ5 have been observed with the small MuSK-MG subgroup in two different studies (ref1, ref2).
Löfgren's syndrome : DRB1*03

Takayasu's arteritis : B*52
Narcolepsy : 
  • DQA1*01:02-DQB1*06:02 haplotype (in combination with DRB1*15:01 in Caucasians); more severe in homozygous
  • DQB1*03:01 worsens
  • DQB1*05:01 and *06:01 protect
  • non-HLA genes : hypocretin/orexin
Psoriasis :
  • B13, B57, B37, B39, C*06:02 (RR = 2-5 in homozygous), DR7 and DR4
  • psoriatic arthritis : B27 (interphalangeal), B38 and B39 (peripheral joints), DR4 (symmetric) and DR7
Fetal neonatal alloimmune thrombocytopenia (FNAIT) :  the immune-dominant antigen leading to severe FNAIT is the human PLT antigen (HPA)-1, whose polymorphism constitutes an epitope for human leukocyte antigens (HLAs) DRB3*0101 and DRB4*01:01

Moyamoya angiopathy (MMA) : HLA-DRB1*03, DRB1*13

Parkinson's disease (PD) : HLA-DRB1*04

Primary biliary cirrhosis (PBC) :
  • HLA-DRB1*08 (P=1.59 × 10−11), HLA-DRB1*14, and  the DPB1 association (DPB1*03:01; P=9.18 × 10−7) are predisposing risk alleles
  • HLA-DRB1*11 is protective (P=1.42 × 10−10) (ref)
ANCA-associated vasculitis (AAV) : HLA-DRB1*0405 might be an independent risk factor for the poor response to treatment and the deterioration of renal function, whereas DPB1*0402 might be an independent risk factor for all-cause mortality (ref).

Immune-mediated bone marrow aplasia : HLA-DR15 allele in patients with MDS appeared to be associated with a good response to immune-suppressive therapy, suggesting that this allele may be a specific predisposing factor for the development of immunemediated bone marrow failure (ref). Secondary graft failure rate at 2 years was lower in patients who were HLA DR15+ (hazard ratio = 0.46, P = .01) (ref).

Chronic beryllium disease (CBD) / beryllium sensitization (BeS) : HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69). Results suggest that the less-frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater risk of CBD (ref).

Acute lymphoblastic leukemia (ALL) : HLA-DPB1*01:01 (ref).

Pemphigus vulgaris : DRB1*04–DQB1*03 or HLA-DRB1*14–DQB1*05 (ref)

Endemic pemphigus foliaceus (EPF) : rs3087456 in the CIITA gene promoter is associated with susceptibility (OR =2.6 and OR=2 for genotypes G/G and G/A)

Autoimmune thrombotic thrombocytopenic purpura (TTP) : DRB1*11 (ref)

Insulin autoimmune syndrome (IAS) / Hirata disease : HLA DRB1*04:06 (expecially in Japanese) and DRB1*04:03 (expecially in Caucasians) (ref)

Idiopathic membranous nephropathy (IMN) : HLA-DQA1 (ref)
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19 comments:

  1. AMEILA TYLERMarch 5, 2019 at 1:30 AM

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  5. Joyce HillaryOctober 16, 2019 at 10:26 PM

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  6. RUTH MARISJanuary 5, 2020 at 8:41 AM

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  7. Suntran MatthewJanuary 25, 2020 at 7:43 PM

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  8. John MyersMarch 17, 2020 at 9:55 AM

    My symptoms started at the age of 47. My fingers on my left hand were stiff and were difficult to move. People noticed that my walk was not normal. I was often asked did I hurt.I noticed nothing different about my walk. It was difficult getting up from a chair and getting out of a car. I was diagnosed a year later, it was the onset of tremors starting in my right hand that caused my other symptoms to be recognized as Parkinson's.I am now 59. With the new herbal medicine i purchase from totalcureherbalfoundation@gmail .com or totalcureherbalfoundatio n.blogspot .com was my only way to get fast relief from this PD,their herbal supplement effectively reverse my Parkinson's disease condition and alleviate all my symptoms. 

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  9. Sallow VillinApril 23, 2020 at 12:28 AM

    Hello viewers in the world am here to share my experience on how I got cured from Herpes through the help of Dr Adigba who use his roots and herbs to cure my Herpes today am healthy and strong once again all thanks to you Dr. may you live long to continue the good work you started, as many of you out there looking for solution to your problems I will like you to give dradigba@gmail.com A try today add him on whatsapp +2348077875210

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  10. martinsMay 28, 2020 at 6:20 PM

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    ReplyDelete
  11. fredrik palmOctober 16, 2020 at 6:41 PM

    I’m recommending Dr Godday to everyone who have herpes virus to get the cure from him. I was diagnose of genital herpes in 2015 and i have been searching and asking questions to see if i could get something to cure the disease because i did not believe what the doctors say that no cure is found yet. I came across a comment on Youtube and the person testify how she was cured from herpes and hpv after using Dr Godday herbal medicine. I quickly contact Dr email and explain my problem to him and he prepare the herbs and send it to me through courier and gave me instructions on how to use it and tell me to go for checkup after usage which i did after two weeks of taken the herbal medicine and my result was NEGATIVE. I waited another month and retested the result was still NEGATIVE and my doctor told me that am completely free from herpes. Am so happy and grateful to Dr Godday for what he has done for me and i will continue to share this for people out there to know that there is cure for herpes. You can contact Dr Godday on email and WhatsApp to get the cure from him. Email:goddayspiritualhome@gmail.com Or Call/What’s-app +1{919}4956404.



    ReplyDelete
  12. Ose WhiteOctober 19, 2020 at 1:09 PM

    I want to share my happiness to the world on how i was cured from (HERPES VIRUS) by Dr Oseremen herbal , i visited different hospital but they gave me list of drugs like Famvir, Zovirax, and Valtrex which is very expensive to treat the symptoms, but i did not have that kind of money to buy the drugs.the one i used before did not cured me. on one faithful day, a friend of my in united kingdom told me about Dr Oseremen herbal, he told me that,it is the herbal treatment that cure is husband from hepatitis B and she told me that he have cure so many people from herpes virus with is herb medicine,then she told me to contact him that he we cure me with is herb . when i contacted Dr Oseremen, he gave me hope and say that i we be cure once i get his herbal, he send the Herbal medicine to me and i take it for two weeks and it seriously worked for me, i went to the hospital to check, my HERPES result came out negative. I am so happy as i am sharing this testimony. My advice to you all who thinks that there is no cure for herpes that is Not true, just contact him and get cure from Dr Oseremen healing herbs, he also have the herb to cure any kind of hepatitis B,C A. AND DIFFERENT KIND OF SICKNESS Remember delay in treatment leads to death.. contact Dr Oseremen on is email at (Dr.Oseremenvadi@gmail.com) or whatsapp him on is Number :+2349056394313 and he we cure you with is HEALING HERB MEDICINE , thanks to Dr  Oseremen for cure me is healing herbs medicine

    ReplyDelete
  13. Success JamesOctober 31, 2020 at 9:39 PM



    I am so Happy to be writing this article in here, i am here to explore blogs forum about the wonderful and most safe cure for HERPES SIMPLEX VIRUS.I was positive to the Virus called HERPES and i lost hope completely because i was rejected even by my closet friends. i searched online to know and inquire about cure for HERPES and i saw testimony about DR Ebhota online on how he cured so many persons from Herpes Disease so i decided to contact the great herbalist because i know that nature has the power to heal everything. i contacted him to know how he can help me and he told me never to worry that he will help me with the natural herbs from God! after 2 days of contacting him, he told me that the cure has been ready and he sent it to me via FEDEX or DHL and it got to me after 4 days! i used the medicine as he instructed me (MORNING and EVENING) and i was cured! its really like a dream but i'm so happy! that's the reason i decided to also add more comment of Him so that more people can be saved just like me! and if you need his help,contact his Email: (drebhotasoltion@gmail.com) You can contact him on WhatsApp +2348089535482 He also have the herb to cure difference cure for any sickness (1) HERPES,
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    (5) HEPATITIS B,
    (6) IMPOTENCE,
    (7) BARENESS/INFERTILITY
    (8) DIARRHEA
    (9) ASTHMA..

    ReplyDelete
  14. james BensonNovember 16, 2020 at 10:21 AM

    I GOT CURED FROM HERPES VIRUS I was diagnosed of HERPES virus and i have tried all I can to get cured but all to no avail,,until I saw a post in a health forum about a herbalist man who prepare herbal medications to cure all kind of diseases including #HERPES virus,at first I doubted if it was real but decided to give it a try,when I contacted this herbalist via his email and he prepared a #HERPES herbal cure and sent it to me via DHL delivery company service, when I received this herbal medicine, he gave me step by direction on how to apply it,after applying the way I was instructed,I was totally cured of this deadly disease called HERPES, all thanks to Dr OGODO Email this great herbal doctor via his email Ogodoherbalhomesolution@gmail.com
    You can also WhatsApp him on +2349044680467
    HE CAN ALSO CURE SICKNESS LIKE
    {1}HIV/AIDS
    {2}DIABETES
    {3}EPILEPSY
    {4} BLOOD CANCER
    {5} HPV
    {6} ALS
    {7} HEPATITIS
    {8}LOVE SPELL
    {9} SICKLE AND ANEMIA
    Only DR OGODO Can Help You I Love You Father.

    ReplyDelete
  15. fredrik palmNovember 25, 2020 at 3:56 AM

    I’m recommending Dr Godday to everyone who have herpes virus to get the cure from him. I was diagnose of genital herpes in 2015 and i have been searching and asking questions to see if i could get something to cure the disease because i did not believe what the doctors say that no cure is found yet. I came across a comment on Youtube and the person testify how she was cured from herpes and hpv after using Dr Godday herbal medicine. I quickly contact Dr email and explain my problem to him and he prepare the herbs and send it to me through courier and gave me instructions on how to use it and tell me to go for checkup after usage which i did after two weeks of taken the herbal medicine and my result was NEGATIVE. I waited another month and retested the result was still NEGATIVE and my doctor told me that am completely free from herpes. Am so happy and grateful to Dr Godday for what he has done for me and i will continue to share this for people out there to know that there is cure for herpes. You can contact Dr Godday on email and WhatsApp to get the cure from him. Email:goddayspiritualhome@gmail.com Or Call/What’s-app +1{919}4956404

    ReplyDelete
  16. Becky DaleJanuary 22, 2021 at 9:05 AM

    My mom ALS started out with a foot drop on her left foot. From there her left leg lost all muscle tone and all the entire left leg muscles were almost gone. Also her fingers and thumbs "contract" at times. Left arm is losing muscle tone too,she have been suffering from amyotrophic laterals sclerosis (ALS) disease for the last seven years and had constant pain which really get us worried, especially in her knees, the only treatment for this ALS (amyotrophic lateral sclerosis) is natural organic treatments honestly ,Multivitamin Herbal Care has the perfect herbal remedy to Motor Neuron Disease including,getting into bed was also another thing she finds impossible. We had to find a better solution for her condition which has really helped her a lot,The biggest help we had was multivitamincare .org today  (or SMS): +1 -956- 758-7882. They walked us through the proper steps, I highly recommend these herbs to anyone suffering from ALS.

    ReplyDelete
  17. Tarsha MichelleMarch 7, 2021 at 7:13 PM

    Hello everybody, i don't just know the reason why some people is finding it difficult to believe that there is a cure for herpes, i have been suffering from herpes since last three years but today i am happy that am cure from it with the herbal medicine of Dr Omongbe the great healer,i was browsing the internet searching for help when i came across a testimony shared by someone on how Dr Omongbe cure his herpes i was so much in need of getting his treatment but after all Dr Omongbe brought a smile to my face with his herbal medicine. I am so happy today that we have someone like this great healer out there, so my people out there kindly visit this great healer on his website https://dromongbenaturalre.wixsite.com/dromongbenaturalreme email address: dromongbenaturalremedies@gmail.com please sir keep your good work cause there are people out there who is in need of your healing medicine.once more contact him now you can call him or whatsApp his number +2348050407265

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  18. JohnApril 11, 2021 at 9:34 AM

    it"s obvious some patients with Herpes Virus are being enslaved to the antiviral and other supplementary Orthodox medicine just to help suppress the virus and not a cure. I have been with the virus since 2015 until I was introduced by a blogger who also narrated her story online on how she was cured of HPV after using Dr ALUDA Herbal Medicine. This is a year and 2 weeks since I was delivered from Herpes VIRUS. All thanks to God for using this Great herbalist to heal me. I have promised to keep telling good things about Dr ALUDA. Please feel free to share Your problems with him and don’t forget to tell him I did refer you to Him. Thanks. Write him on whatsapp +2348145636867 or mail him @ Draludaharbalhome @gmail. com He deals with Alzheimer virus, Cancer, HIV, Herpes, Genital, warts, ALS, HBV, UTI, Virginal infection, Genital, Wart, HPV, Hepatitis A/B, Good luck, HSV,  Cold Sores, Diabetes 1 & 2, Pregnancy, Ex back.

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  19. Jones RosarySeptember 3, 2023 at 12:27 AM

    All Thanks to Dr Agumba for the ALS treatment and it works perfectly. Everyone has to understand there is no harm in trying. My dad is 100% fine after using dr agumba ALS product. I'm so happy about it. and I do believe in natural herbs right from the beginning because it's better and more ative. Anyone who needs ALS natural reversal or every other deadly disease to get cured, here is Dr Agumba Email dragumbasolutioncenter@gmail.com his whatsapp +2349032173881 .

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