HLA Question

jeffmarquez

0 Posts
Reply HLA Question Posted on: Apr 3, 2011 at 5:14am
Hi Dr. Braverman. I’ve been following you for a while and had a couple questions for you. We are patients of the Alan E Beer center. We’ve been under their care for 16 months. We’ve had 2 m/cs. We think caused by our immunology.

Some stats:

Pre-treatment, now
Elevated NK Activity 50:1 = 37, now after doing IVIg 14
Elevated CD3CD56 = 17, now 8.7
Cytokine: TNF-a/IL10 = 40, down to 25 after Humira, now back at 39
LAD Bcells IGG = 10, 95 in July, now 70, we did LIT 4 weeks ago and will get tested soon
t-reg: 0.4, now 0.6

She’s MTHFR hetero, PAI-1 hetero, slight AOAs (she tested positive, but when measured level it was on the lower side), no antiphospholipids thankfully, no ANA

We are a DQ Alpha match. We are both 201 and the dreaded 501.

We’ve done 5 LITs, 4 IVIgs, 2 two shot doses of Humira. Her body responds reasonably well.

Back in feb of last year, we got pregnant after 2 rounds of LIT. Her LAD Bcell IGG was 35 and her NK activity was slightly elevated (50:1 -> 21). CD3CD56 was 10. She also formed a blood clot right next to the embryo so it’s possible that caused the M/C. Week 7, heartbeat. Examination of the DNC was good: no elevated NKs at site, evidence of t-regs.

We got pregnant again last Oct. Immune numbers were good going into cycle but her 50:1 spiked to 30 upon pregnancy. Poor little embryo only lasted 5.5 weeks. No heartbeat.

We’ve done 2 IVFs (11/09, 6/10), both unsuccessful. Both times we got pregnant it was natural. She’s taking DHEA now that we think has contributed to better egg quality. Both IVFs were done without doing DHEA. Both pregnancy she was taking DHEA for at least 3 months.

Our treatment is to be as aggressive as possible. We’ve been TTC the last 2 months. Did Humira in January, and started TTC in feb. LIT works well in lowering NK activity, so we have gone twice in the last 2 months. in cycle 1 (Feb), her NK activity 50:1 was down to 9 and her cytokines 25. We also did IVIg right at potential implantation just to be safe. This second cycle (March) we did LIT at CD6 and again IVIg at CD 21 (her 50:1 was 14 and cytokines went up to 39 (!)).

So anyway, my questions:

You have some literature on HLA. The Alan E Beer center stopped testing for DQ Alpha match, but since we are THE EXACT DQ Alpha match I wonder if it caused the NK activity to spike so much in our second pregnancy. Looks like the DQ Alpha itself isn’t enough and that you need HLA DRB1 03 as well. Can you recommend the HLA tests that we should take? Also, what is the treatment besides staying aggressive with LIT and IVIg? (We have no yet tried Intralipids).

Since we have a DQ Alpha match, we have a 25% chance that the embryo will be 4.1/4.1, which in theory is a big problem. I also read that the embryo having the same combo as the mom is a problem. So a 201/501 is 50% chance. So the only good pair is 201/201. Is that right? That sucks!

If we were to do IVF and we passed more than 1 embryo, is it possible that the 501/501 could mess it up for the entire batch of embryos? Meaning, if her NK activity increases with the presence of 501/501, then the other non 501/501 get attached as well?

I appreciate your help.

-Dad2B

Dr. Braverman

1998 Posts
Re: HLA Question Posted on: Apr 3, 2011 at 7:05pm
Your information was quite extensive and on the surface i do agree there are immune issues at work here. There is certainly more to HLA than DQalpha and we have many documented couples with dQalpha matches but clean on all the other HLA's and have successful pregnancies, you certainly need the remainder of the HLAs screened to at least rule out "syngenic" pregnancy as a cause of your issues. Its too simplitic to look at this in terms of the DQalpha as you know dqalpha is not even present on the surface of the invading trophoblast, it may be the function of the other HLAs at play here. I would really need to spend a little time with you and go over your entire history to give you a worthwhile opinion at which time we could discuss other therapies that we have been using here with great success. I do beleive you have to be just as careful not treating sometimes as treating and meticulously follow the paramters of many fot he cellular components throughout the treatment.
Feel free to call my office and schedule a consultation with me, ask for Kim she will arrange all for you.
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.

Dad2Be

0 Posts
Re: HLA Question Posted on: Apr 11, 2011 at 10:07pm
Thanks Dr. B. We will try to schedule something with you.

Hope it's okay that I ask another question. Our RE wants us to consider ZIFT. He believes we have an egg quality issue (she's positive for AOAs, we had 6 eggs last IVF) and thinks that we should have the eggs out of the body for as little time as possible. I have read a lot about DQ Alpha match and avoiding a multiple embryo transfer. I understand that DQ Alpha match is just one component and that there are other HLA factors to consider. I also read that with ZIFT there are dying embryos mixed with great embryos. Dying embryos give off Reactive Oxygen Species which can cause inflammation. Also, the increase in number of embryos can increase the immune response to all of the embryos.

What is your opinion on ZIFT? Cheers.

Dr. Braverman

1998 Posts
HLA question Posted on: Apr 15, 2011 at 4:30am
I no longer see a good reason to use Zift. you are correct about ROS and its antagonstic affect on implantation and fertlization. DQalpha matching is only a small component of the necessary HLA screening that should be performed and you cant draw conclusions with just the DQalpha information(see my discussion on HLA screening on the website).
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.

Dad2Be

0 Posts
Re: HLA Question Posted on: Apr 28, 2011 at 1:53pm
Hello.

Do you mind telling me what HLA genes you test for? The scripts I've seen test for HLA A, B, C, DQ and DR. But from your site it looks like there are others that are important.

HLA A
HLA B
HLA C
HLA G
HLA E
HLA F
HLA DR
HLA DQ
HLA DP

Thank you.

Dr. Braverman

1998 Posts
Re: HLA Question Posted on: May 3, 2011 at 11:41am
they are all important , some denote conditions that are compatible with RPL and others show compatibility at greater detail than just the small numbers of HLA that many test for.
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.

Dad2Be

0 Posts
Re: HLA Question... Consult scheduled Posted on: Jun 30, 2011 at 6:14am
Hello, we have a consult scheduled for July 19. We are really looking forward to speaking with you. We had our 3rd miscarriage last week. To our surprise the embryo was chromosomally normal. Our RE was convinced (before we got the test results) that it was a chromosome issue based on the ultrasound. Also we are a 100% DQ Alpha match. I would love to test all other relevant HLAs before our consult to save some time and have more information to discuss. Is that possible? Can you fax me a script? We have a lot of experience sending blood all over the country! I will send all medical and immune documents and completed form to your office.

Thanks in advance for all your help. You are our last stop before adoption.

Dr. Braverman

1998 Posts
Re: HLA Question Posted on: Jul 3, 2011 at 2:12pm
I beleive we handled the HLA request for you. It is certainly necessary to see all of the HLA testing as the DQalpha alone is not relevant. I look forward to speaking with you. Im sorry for your last loss, I really feel I can correct this.
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.