Has there been much evidence of genetic link for Lupus

[Lizziequink]

Over the past several months I have been asked a number of times if any family members have Lupus as it is one of the identifying factors during diagnosis. Up to now I have been able to give a definitive answer. I recently made contact (via a genealogy search) with 3rd cousins (on my maternal grandmother's side of the family) in Canada, one of whom I have discovered today was diagnosed with Lupus in her 30s. My mother was mostly pretty unwell for many years before her death from cancer of the liver at 54, but my grandmother died of old age at 84. Is there any evidence that a genetic link going back further could be possible? My cousin's email today has got me really curious.

[Boudica1]

That's a very interesting question. I do know on my father's side of the family there are at least 2 AI diseases linked to skin and some type of skin problems. Also my father's grandmother had a undiagnosed facial rash and some problem with balance just before she suddenly died in her early 50s and her sister died in her late 20s. But as both ladies lived out in the sticks with a GP who trained in the army in the first world war the family never got to the real reason and with one of the deaths were very angry at the dr's reason.

All I can say is that I am now having annual blood tests for ANA and Complement c3 and c4 so someone somewhere suspects something just not keeping me fully in the loop.

Good luck with your quest.

X

[Lizziequink in reply to Boudica1]

Thanks so much for your reply. My husband pointed out today that it's more than likely previous generations weren't aware of Lupus by name, just as Diabetes wasn't fully understood until almost 100 years ago. Prior to that people with it just died. My dad was diagnosed with Type 1 in his 50s. That was in the early 1970s and he had to use animal insulin products using glass syringes that had to be sterilised in a metal dish. By the time my daughter was diagnosed in the early 1980s research had come a long way in less than 10 years, and within another 10 was using synthetic insulin and disposable syringes and 20 years further on abdominal inserts became available.

In think what I'm trying to say in a very long-winded way is that things are recognised and understood far more now than they ever were. I suspect that so many times we're being kept out of the loop because the so-called experts are learning as they go along. Hope you get some answers soon and I'll let you know if I get any answers to my questions. x

[Jmiller623 in reply to Lizziequink]

Type 1 diabetes has a clear genetic link to HLA-DR4 DQ8 or DQ2 allele. These code for recognition proteins on your immune cells so you don’t attack your own body. My father also got type 1 diabetes at age 34 long before the link was found. My paternal grandfather had hashimotos - also linked to DQ2/8 as is celiacs. Per my genome sequence, I inherited this as well. However, I do not think it causes lupus but can be one of many genes that interact together with other immune genetic defects to cause lupus by altering expression of key immune system genes.

[Jmiller623]

Hi Lizzie! There are plenty of publications linking some genes to susceptibility of lupus based on genome wide studies. All you need to do is plug in lupus genetics into Google scholar. Many genome wide studies have been done but there’s not typically one gene that tells all. Much of how lupus develops has to do with environment and a nidus for development. For me, I think it was EBV, maybe repeated flu vaccinations and then bacterial pneumonia. A new publication linking EBV to lupus development was just recently published.

ncbi.nlm.nih.gov/pmc/articl...

Although a little outside the realm of laymen research, I did 23andme (mail in genetics profile) and looked at my raw data. I have a polymorphism in a gene called CTLA4 which is a master regulator to help dampen the immune system. The polymorphism has been linked to lupus per SNPedia. I definitely think there are familial genetic components but there also must be a perfect storm of exacerbating factors for it to develop. This is why even if the abnormal version of a gene is present, it may not predict who gets lupus and who doesn’t.

I come from a family of nothing but autoimmune disorders. Runs strong on paternal side. My sister and dad have many of the same symptoms I do, just not as severe. On top of that, I am now developing some serious GI problems and my mom has Crohns so I may be in a perfect storm situation.

Hope this helps!

[Lizziequink in reply to Jmiller623]

Thanks for that. I'll have a look at the link you sent.

[Buckley123]

I think it’s autoimmune in General

My mum had ms and now I have uctd my Nan has sticky blood ect xx

[Lizziequink in reply to Buckley123]

Thanks you Buckley

[Jmiller623]

I am an internal medicine physician with an MD PhD earned from a very well respected university. I am well aware of the differences between type 1 and type 2 diabetes. There are clear HLA allele polymorphisms linked to type 1 diabetes. This was established long before type 2 diabetes links. These are not genetic mutations. They are single nucleotide polymorphisms which effect the expression of genes or functions of proteins once folded. Hashimotos and Celiacs are both linked to these polymorphisms which are also implicated in autoimmune polyendocrine syndromes which likens to the pathology behind Sjogrens. Sjogrens is usually caused by lymphocytic infiltrates whereas some polyendocrine syndromes are caused strictly by auto-antibodies.

Publication in support:

sciencedirect.com/science/a...

[Jmiller623]

Maybe. I think a lot of the information is meant to communicate in simplistic terms. Since there is no one gene or mutation that has been linked to lupus, it’s hard to say there is a clear genetic cause. I think it’s just easier to just say that there have been no clear genetic links. I have asked Paul Howard to comment on EBV link but there’s not much info beyond the glandular fever link.

Otherwise, if you cited specific genes that may play a role, you’ll have patients running to their docs asking for them to test them for certain mutations that don’t have approved methods of testing. It’s easy to type people with regard to HLA alleles. It’s done millions of times a day with bone marrow donors and recipients so the accuracy and efficiency of such testing has been well vetted.

I’d love to help with some literature on here. However, I am from the US and administrators on here are employed. Unfortunately, it would fall outside my boundaries to suggest edits for a charitable UK forum. I am always more than happy to discuss on forum as you can see. ☺️

[Jmiller623]

Apologies.

Regards

[DaftCat]

My cousin had lupus. I think there must be a link.

[Lizziequink in reply to DaftCat]

Thanks DaftCat. I'm getting so much response to my question and the more I read the more I'm convinced there must be a link.

[Treetop33]

Yes I understand there is. My aunt died of Lupus and my mum had clear signs of it but was never diagnosed (mood-regulation problems, hair falling out, facial flushing, exhaustion, UTIs etc etc). I actually can't get her to take it seriously now, either. My sister has ulcerative colitis.

Even though it takes a few years to get taken seriously now (yes, yes, oh docs, we are hysterical...of course!!!) at least we are diagnosed and there are some treatments. I am educating my nine-year-old daughter on how to stay healthy on the premise she may carry a predisposition and should avoid doing things that might trigger it.

[Lizziequink in reply to Treetop33]

Hi Treetop. I find it so hard to understand why consultants are so closed and defensive about our health when it's us who are suffering from it. I'm pretty sure if it was then they'd be more understanding.

[Heatheric]

My dad had lupus, his rheumatologist at the time (1970s) had an interest in lupus - no specialist centres then! I remember him being told that whilst there was no evidence that it was hereditary, there did seem to be a familial tendency. As it happens, I was diagnosed with lupus 10 years ago (I'm 65 now) and both my brothers developed rheumatoid arthritis in their early 60s. Funny old thing the immune system, isn't it! Heather

[Lizziequink in reply to Heatheric]

Hi Heather, thanks for that. I think that maybe supports my reply to Bessy01.

[Bessy01]

I have SLE & fibromyalgia diagnosed since 2010 then in 2017 my daughter was diagnosed with the very same. I asked if it was genetic, her consultant said yes mine said no.

[Lizziequink in reply to Bessy01]

Makes you wonder doesn't it. I suspect sometimes if that might be down to a difference in the ages of your consultants. I believe that the younger the are, the more current their training and the more open they are to all possibilities.

[Salzer]

Such an interesting question! I've thought a lot about this recently as in recent years my son has developed type 1 diabetes, I've just got a provisional UCTD diagnosis and AI hypothyroid is likely on its way and my husband has developed vitiligo! There isn't a history of autoimmune in my family at all and only thing on his side is a great grandmother with late onset type 1 diabetes (LADA). My son's endocrinologist said that was so far back it's unlikely to have been very relevant to my son's diagnosis. So where is this all coming from? I have wondered if it's environmental or maybe as others have said, there were undiagnosed AI conditions there in the family history. Having no known family history has certainly made getting a diagnosis more difficult for me though 🤔

[Lizziequink in reply to Salzer]

Hi Salzer. My husband was adopted and we've been unable to follow up on his parentage. I've seen how frustrated he gets having to tell medics he has absolutely no idea of natural parents' health history so can understand how Difficult it must be for you.

[Buckley123]

For my understanding which is not a lot of you have the 🧬 gene it is most often activated by emotional stress like when my mother died i became ill and my mums was most certainly having a child

And my Nan was over worked had angina lost a few babies so that emotional stress also xx

[Babs511]

Hi I thought you might find my family health of interest in regard to your question. I have lupus SLE and Raynaud’s and sjogrens. At first I thought I was the only one. But after making contact with various members of the family I can trace everything back to my Grandfather. I have a cousin with hashimotos disease, several with Raynaud’s and fibromyalgia and a lot of relatives with blood tests showing inflammation in their results. So I think speaking for me and mine and as does my rheumatologist there’s a very strong genetic link.

[Lizziequink in reply to Babs511]

Thanks Babs. I've been inundated with responses to my question, the majority of them backing up the theory of genetics. They've given me so many pointers I need now to research. Thanks again.

[Buckley123]

I’m told I have ptsd from watching my mum and caring for her from a child up until last year xxx

[Lizziequink]

Very interesting Pippa. I had glandular fever in my 20s but had completely forgotten till you mentioned it. I'll certainly do some research into that. Many thanks

[junemc]

I am aware there is a genetic link to auto-immune diseases in general. My mother has rheumatoid arthritis. I have coeliac disease, I had sarcoidosis and I may have lupus. I read that 25% of people with one auto-immune disease will develop another. Some people have multiple auto-immune diseases. Even the useless rheumatologist that I saw acknowledged there could be "clusters". Still didn't help me to get a definite diagnosis for lupus though! As other members have mentioned, it is quite difficult to go back into family history due to lack of knowledge about auto-immune diseases in the past.

[Lizziequink in reply to junemc]

Thanks you, that kind of backs up my theory that there has to be a genetic link. I have RA, Sjogren's, Reynaud's and all the symptoms of Lupus and a number of other conditions that may or may not be caused by auto-immune issues such as bronchiectasis and liver problems that were diagnosed prior to the RA diagnosis so were never take into account. Someone on the site also fed back that a link to glandular fever which I had in my 20s but had completely forgotten about has also been raised, so who knows what else my original question might raise. Just remembered my mum mentioning that she'd had rheumatic fever when she was young, so there may also be a link there too.

[Lizziequink]

I knew some of the story but not all of it. Thank you for sharing it with me.

[Lizziequink]

Hi again Pippa, that has been suggested to me outside this forum. I had a really nasty fall a year ago resulting in broken shoulder blade and a mangled elbow that had to be replaced and many of the additional problems I have started after that. Looking on the bright side though it did give me the opportunity to set the alarms off going through security when flying back from Rome in September. I really should either learn to speak Italian or holiday in the UK in future