Auto-immune disease association with aHUS?

[Elizabeth Farrell]

My question - is there a possibility? I read somewhere that if genetic testing came back negative that auto immune deficiency should be investigated. We only recently had the results of our daughter's genetic tests (which were negative) and when I mentioned the auto-immune avenue to our consultant he was happy to go down the route of investigation. There is a high incidence of auto-immune disease in my family and I would love to know if this could be a trigger or facilitator of aHUS. Is there any evidence out there?

[Kerri Grey]

Hi Elizabeth,
My son's genetic testing came back negative also. If you find out any more info please let us know because it would be great to have a definite answer about this disease.
Cheers Kerri

[Elizabeth Farrell]

Hi Kerri
I know how you feel about wanting a definite answer! It does your head in doesn't it? I would be happy to let you know Amy's results when we get them, but the genetic testing seemed to take forever, so I don't know how quickly these results will come through.Hopefully, will be posting soon. Liz

[Kerri Grey]

Thanks Liz, will look forward to hearing from you...

[Bill Biermann]

Two answers:
Atypical HUS can be "triggered" by a large number of events. That does not mean that the event "caused" the problem. Rather, the event set off a serires of events, and a weakness in the body (A-HUS protein) set off a series of cascading events.
The term "auto immune" is a somewhat broad category, but Atypical HUS is now classified as Complement Related. Now Complement is part of the body's immune system that operated in what is called the "alternate Pathway" . So really, the Complement related
The complement system is a biochemical cascade that helps, or “complements”, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by the adaptive immune system.

The complement system consists of a number of small proteins found in the blood, generally synthesized by the liver, and normally circulating as inactive precursors (pro-proteins). When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end-result of this activation cascade is massive amplification of the response and activation of the cell-killing membrane attack complex. Over 25 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. These proteins are synthesized mainly in the liver, and they account for about 5% of the globulin fraction of blood serum.
So in a broad sense, Atypical hus, based on what we know, is an immune disorder.

Now the good news: The Foundation will be funding a study that aims to identify these "missing" genes. MOre on that to follow

Hope that helps

Bill Biermann

[Linda Burke]

Phewww- thanks for taking such a complex issue and simplifying it for us all. Still, it rather makes one's head spin...or is it just me? 8-D

Bill Biermann said:

Two answers:
Atypical HUS can be "triggered" by a large number of events. That does not mean that the event "caused" the problem. Rather, the event set off a serires of events, and a weakness in the body (A-HUS protein) set off a series of cascading events.
The term "auto immune" is a somewhat broad category, but Atypical HUS is now classified as Complement Related. Now Complement is part of the body's immune system that operated in what is called the "alternate Pathway" . So really, the Complement related
The complement system is a biochemical cascade that helps, or “complements”, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by the adaptive immune system.

The complement system consists of a number of small proteins found in the blood, generally synthesized by the liver, and normally circulating as inactive precursors (pro-proteins). When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end-result of this activation cascade is massive amplification of the response and activation of the cell-killing membrane attack complex. Over 25 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. These proteins are synthesized mainly in the liver, and they account for about 5% of the globulin fraction of blood serum.
So in a broad sense, Atypical hus, based on what we know, is an immune disorder.

Now the good news: The Foundation will be funding a study that aims to identify these "missing" genes. MOre on that to follow

Hope that helps

Bill Biermann

[Elizabeth Farrell]

Hi Bill
Thanks for the info. Having now read it 3 times I think I get it! I have realised over the last 2 years that the saying "a little knowledge is a dangerous thing" is totally true, so my aim is to know and understand as much as I can about this disease/condition.Your explanation of the Complement system has been very helpful. It has also made me think thet maybe finding the cause of Amy's aHUS isn't as important as I thought.I guess knowing the cause, or trigger,would just be one less question on the list! Looking forward to the forthcoming research. Thank you.
Liz




Bill Biermann said:

Two answers:
Atypical HUS can be "triggered" by a large number of events. That does not mean that the event "caused" the problem. Rather, the event set off a serires of events, and a weakness in the body (A-HUS protein) set off a series of cascading events.
The term "auto immune" is a somewhat broad category, but Atypical HUS is now classified as Complement Related. Now Complement is part of the body's immune system that operated in what is called the "alternate Pathway" . So really, the Complement related
The complement system is a biochemical cascade that helps, or “complements”, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by the adaptive immune system.

The complement system consists of a number of small proteins found in the blood, generally synthesized by the liver, and normally circulating as inactive precursors (pro-proteins). When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end-result of this activation cascade is massive amplification of the response and activation of the cell-killing membrane attack complex. Over 25 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. These proteins are synthesized mainly in the liver, and they account for about 5% of the globulin fraction of blood serum.
So in a broad sense, Atypical hus, based on what we know, is an immune disorder.

Now the good news: The Foundation will be funding a study that aims to identify these "missing" genes. MOre on that to follow

Hope that helps

Bill Biermann

[Theresa Pereira]

Olivia's results all came out negative. We had an appt with the nephrologist this week who explained trigger can be either auto immune or genetic. We pray it's auto immume that can be out grown or "self corrected" as opposed to genetic, well there is nothing you can change about that!!
There are excellent labs in France and Italy studying HUS. Discuss with your Dr to maybe send bloods there.

[Kerri Grey]

Ashley had his genetic testing sent to France and to UK...they apparently both test for different mutations...both came back negative!!!

Theresa Pereira said:

Olivia's results all came out negative. We had an appt with the nephrologist this week who explained trigger can be either auto immune or genetic. We pray it's auto immume that can be out grown or "self corrected" as opposed to genetic, well there is nothing you can change about that!!
There are excellent labs in France and Italy studying HUS. Discuss with your Dr to maybe send bloods there.

[Linda Burke]

Hi Kerri,
We had Hunter's blood sample sent to Dr. Remuzzi's lab in Italy (he and his team are credited with many important aHUS articles), then when the University of Iowa began its aHUS genetic testing program we sent both boys blood samples there for testing (see the Links box on this site's Home Page).

[Kerri Grey]

HI Linda,
Did you get the same results from both of the labs or did you get different results???

Linda Burke said:

Hi Kerri,
We had Hunter's blood sample sent to Dr. Remuzzi's lab in Italy (he and his team are credited with many important aHUS articles), then when the University of Iowa began its aHUS genetic testing program we sent both boys blood samples there for testing (see the Links box on this site's Home Page).

[Linda Burke]

The same results at both labs for Hunter, factor H with a mutation at the terminal end SCR 20, a 'hot spot' for aHUS mutations. Skyler was only screened at Iowa, sad to say with the same results: factor H, SCR 20.

Kerri Grey said:

HI Linda,
Did you get the same results from both of the labs or did you get different results???

Linda Burke said:

Hi Kerri,
We had Hunter's blood sample sent to Dr. Remuzzi's lab in Italy (he and his team are credited with many important aHUS articles), then when the University of Iowa began its aHUS genetic testing program we sent both boys blood samples there for testing (see the Links box on this site's Home Page).

[Kerri Grey]

Thanks Linda, i dont know whats worse to know or not to know. Are you saying that you think Ashley should have his genetic testing done somewhere else. Do these other labs that you have mentioned offer more extensive testing...i dont know much about the testing side of things all i was told is that the UK tested some when that came back negative more were sent to France and was told about 6 weeks ago that they also came back negative i know another a little girl who was diagnosed after ashley and she has tested positive to aHUS factor H she had plasmaphersis for about 8 months and has been completely fine...no longer has plasma, never had dialysis, and has had no flares.

Linda Burke said:

The same results at both labs for Hunter, factor H with a mutation at the terminal end SCR 20, a 'hot spot' for aHUS mutations. Skyler was only screened at Iowa, sad to say with the same results: factor H, SCR 20.

Kerri Grey said:

HI Linda,
Did you get the same results from both of the labs or did you get different results???

Linda Burke said:

Hi Kerri,
We had Hunter's blood sample sent to Dr. Remuzzi's lab in Italy (he and his team are credited with many important aHUS articles), then when the University of Iowa began its aHUS genetic testing program we sent both boys blood samples there for testing (see the Links box on this site's Home Page).