Trying to analyze HLA-B27 and PGD

What is HLA-B27? Oooh there are many subtypes of HLA-b alleles.
HLA-B*2704 , B*2705, B*2709 etc... Scandinavian countries has high incidence of uveitis. Equatorial counties has fever incidence. Wait, does this have something to do with the sun? Vit D deficiency?

Nicholas J. Sheehan,  Rheumatology 2010;49:621–631. Http://rheumatology.oxfordjournals.org

In Taiwan Chinese, susceptibility to AS is determined by homozygosity for HLA-B*2704, whereas B*2705 may confer protection [23]. 

It has been suggested that B*2709 arose in the Mediterranean region by a single mutation from B*2705 on a haplotype associated with low susceptibility for AS and that it is the haplotype that is more important for disease predisposition than the immunobiological differences between B*2705 and B*2709 [19].

In contrast with an early report [40], a recent Finnish study showed that HLA-B27 homozygosity is associated with a moderately increased risk of AS compared with B27 heterozygosity [41]. 

AS develops at an earlier age in patients who are HLA-B27+ than in those who are HLA-B27(negative)[42, 43]. In a Chinese population, the earliest age of onset of AS is associated with the HLA-B*2715 subtype [43].


Wait ya... The alleles are getting more diverse. Not all ankylosing spondylitis patients are HLA-B27 positive. I saw another article citing ankylosing sponylitis HLA-B27 negative father and son. HLA-B27 being the most popular, other genes may also be the culprit. My genetic study might be a waste of resources. 

Genetics, to me, is getting complicated. Homozygous- means two genes are affected. While, heterozygous mean only one gene is affected. This reminds me of the Mendelian matrix again. Father x mother. During the fertilization, what is the chance that the embryo will get two HLA-B27 alleles from me? Am I homozygous or heterozygous HLA-B27 positive? What is the PGD standard operationg procedure? Discard all embryo with HLA-B27, even if that is heterozygous? Do I still need a geneticist consultation? This reminds me of my immunologist remarks: I am playing god. I said I am just embracing what technology has to offer. Ooops, few month ago, I wish to have PGD because my husband has genetic translocation. After the retest was done, it says normal chromosome. ai... PGD or not? Pray and trust God! 

Actually, I dont want to make my decision. I dont want to be guilty in the future. I have to opportunity to have PGD done and but I turned it down. What if, It so happen that my child does not have ankylosing spondylitis but he has Down syndrome? Advanced age moms are at high risk of bearing aneuploidy offspring.

My apical lung lesion ordeal

Who should I blame for the apical lesion scare? The radiologist or my immunologist who had amplified the findings?

A decade old letter from the rheumatologist says: she asked for xray baseline of my lungs because TNF-alpha and glucocorticoid may cause fibrosis. I went to visit my rheumatologist. Time travels so fast, unknowingly, 12 years has lapse since my last visit. This also means, that I am in remission. I asked her for her input on my xray films. She said x-ray film is clear. I said my immunologist said I have smoker's lungs and that lesion maybe a koch's lesion. I maybe put in immune suppresant. I need a pulmonary clearance from her. Was the scar caused by tnf-alpha or tuberculosis?

She said since I am in remission, it is not caused by TNF-alpha. It maybe caused by tuberculosis. Ok noted! I asked: Where is the lesion? Xray report says in the apical right lung. She replied, the radiologist is too good to see that small lesion. She feels it is clear. Ok noted again! Do I need to see a pulmonologist? She said the proper doctor to consult is an infectious disease doctor. So, he can rule out whether I had tuberculosis infection or not.

I then went to an infectious doctor. I told her I have an apical lung lesion, I suspect it is tuberculosis. What shall we do- what is tuberculin skin test? How do I know if the scar is new or old? Worst case scenario, if that were a Koch's lesion, what shall we do? I noticed she did not read my xray film. She just read the xray report. She suggested a tuberculin skin test. But, I will be going abroad I cannot come back after 48hours. I rescheduled the tubercullin skin test. I also told her I fear for a false positive. I told her I may have delayed cytotoxic hypersentivity reaction. She said it was meant to be that way.

Ring ring... Wow, I got a slot for consultation from by beloved immunologist. I tried my best to move him. I told him that I was bothered by his comment that I have smoker's lungs. And I am dying and yet he had not referred me to a pulmonologist. He laughed at my tuberculin skin test. What is the worst case scenario? He said he can put me on minimal immunosuppression + IvIg.

The pulmonologist said my xray is clear. I said the chest PA is clear but he needs to read the apico lordotic view. He laughed out loud and said it was clear. I showed him the xray report. He said my lungs are clear. No smoker's lungs also.

Bad immunologist! Same old comment: he is trying to kill a mosquito with a cannon ball. ^.^

I see this scenario as somebody sharing rumor about my trusted cashier in our store. When I secretly get feedback from her colleagues, I found out majority of the people can attest that the cashier is honest. But a selected few loyal staff will say otherwise. I am not zeroing out the possibility. I still trust to some extent. Deep in my heart, I believe the possibility that my immunologist theory is true. I close this issue for now.

No more Preimplantation genetic diagnosis

We have different belief with my obgyne and immunologist. What shall we do with the abnormal embryo? My answer is quite simple: discard the abnormal embryo!

My immunologist said I will not exist in this world if my parents did a preimplantation genetic diagnosis on me. I said I am not playing Hitler or God. I just want to embrace science.  He held my hands then I cried. I said I don't want a child with juenivile arthritis. His words reverberated til this morning.

Btw, what is the mechanism of the inflammation- how does HLA-B27 promote inflamation? If I look the other side of the coin, seronagativity to HLA-B27 does not mean you will not have ankylosing spondylitis. Seropositivity to HLA-B27 does not necessarily mean a person will have spondyloarthropathy. I need to consider recessive and dominant trait also. Grrr... What is HLA-B27, a dominant or recessive allele? This reminds me of the Mendelian Matrix from high school biology. I somewhat understand his point. I am trying to digest its meaning.

I just detected an inflammatory marker-- HLA-B27 , the allele. I never did the genome sequence in the past. I need to know the gene sequence to probe in my embryos. I guess this is a polymerase chain reaction.

He said I begin to think with the same wavelength. As of this moment, I feel I don't want to do PGD yet. I maybe throwing away life. Ai... Need to reconsider this.

If the belief of doctors here in Philippines that life starts at embryo stage, I guess I will not be able to schedule a geneticist appointment. I told her secretary I want to do PGD in Taiwan. By the way, PGD is banned in the Philippines.

Visited obgyne again

I feel unease. I feel there is a need to get a pulmonary clearance. I feel she thinks my apical lung lesion is a Koch's lesion. Btw, why did she not give me an action plan. I asked her today whether I need to go to pulmonologist , rheumatologist or immunologist first.

Pre implantation genetic diagnosis

About half year ago, my husband's first chromosome karyotype says he had a reciprocal translocation. But, it failed to establish that he has more than one cell line. And what does this mean? Huhuhu, I cried. I checked the net with 46,xx balanced translocation the chance of conception is less than 20 percent.  I don't want abnormal kids.

I went to consult a geneticist. She then suggested that my husband and me to have karyotyping in the state hospital. This is to rule out mosaicism for both of us. She then asked why did I not have my karyotype tested together with my husband? My naive answer was: whether my chromosome is good or bad, it will not prevent me from trying to conceive. Whew! Luckily our karyotype results were normal.

I though our genetic issue is over. I don't have to be put into maximum dose ovarian stimulation. Thank god, I thought I dont need a very aggressive therapy.

I confess that I did not share my entire autoimmunity story to my doctors. On my last consultation, my immunologist said he needs to see a psychiatrist. He complained that I am driving him crazy. Why I am feeding him one small piece of info at a time? On my last consultation with my obgyne she also commented that I should have given to her my 'decade old letter' on day1. Bad me! I just do not want to be misdiagnosed because of my biased info.

Anyway, I tried to be very open in my new IVF inquiry yesterday. I partly regret me and my big mouth. I was required to go to Taichung, just to have some basic immunologic tests. I cannot send out my blood via courier. I need to personally go to Taichung. Grrrr... Then I tried my best to explain what is ankylosing spondylitis. It is a spondyloarthropaty caused by HLA-B27 gene. My main problem is TNF-alpha.

Oopss... What HLA-B27 gene? Do they heard it right? GENE? I need PGD pre implantation genetic diagnosis. Whatever... Now, PGD sounds like a brilliant idea to me. I should thank my big mouth!

Apical lungs lesion

What is lungs granuloma? What causes Apical lesion? Is my immune system attaching my lungs? It thought my lungs are foreign? Oh my god!

I am disturbed with my immunologist comments. My xray looks like a smoker's lungs. Anyhow, he gave me a go signal to under IVF already. He will not mind my skin reaction result of my LIT since my laboratory report shows I have 100% PRA already. TNF-alpha maybe responsible for the pustules.

Post 5th LIT consultation

I had developed pustules in the 3rd and 4th LIT. Is LIT really the ultimate treatment for my underlying immune problem? 5th LIT is a make or break. I should not exposed to any sick person- virus or bacteria. Should I be wearing a bunny suit to work? I told myself: after my 6th LIT, with or without my doctor's consent, I will push through with my IVF plan.

Sad enough, I had developed pustules again in my 5th LIT. My immunologist new task is to find out what is causing the infection. Chest X-ray, hepatitis test and pap smear were requested.

Chest X-ray: previous x-rays were PA view and lateral view. Recent test includes the apico oblique view. The impression was: I have small lesion in the apex of the lungs. This is usually not visible in the PA and lateral view. How can the radiologist conclude that it was an old lesion? It may be an active tuberculosis. Uhu Uhu Uhu... Uhu.

Hepatitis: negative

Pap smear: no result yet. The obgyne's remark was no sign of infection.

Uhu Uhu Uhu... I have tuberculosis. How can this be? I never did the apico oblique xray view of chest before. What if I had that lesion 2 years ago? But two years ago I had taken prednisone for my two bouts of uveitis. In theory, when my immune system was suppressed, it may have given the opportunity for tuberculosis to grow. I had prednisone again last year. Oh no, my tuberculosis is quite new. Uhu Uhu. Sorry, if I spread my tuberculosis germs while you were reading my blog. Uhu.

Out of no where, I found a decade old letter. My rheumatologist wrote a letter to the referring doctor. The letter mentioned I had taken several months of nsaids... and I had took methotraxate... I also mention tnf-alpha and infliximab. I says have ankylosing spondylitis. It says my rheumatologist requested and xray to serve as baseline since apical lungs lesion maybe a part of ankylosing spondylitis ... Suddenly, my immunologist changed his perception. He then commented I was driving him crazy. Why am I feeding him small fragment of info at a time?

Anyway, I thank that letter. My obgyne has also commented I should have submitted to her that letter on day1. I smiled and replied: I am stubborn. I may not believe in her until I tried.

Grr... granuloma sounds scarry.