Birdshot is an inflammatory disease, and if we can find out why we produce this inflammatory response, we may be well along the way to finding a cure. Continue reading
The next Birdshot Day will be held on 28 September, 2013 in Boston, United States. It is being hosted by Stephen Foster, whom many of you will know. Stephen has been an inspiration for all of us with Birdshot, and held the very first ever Birdshot Day in Boston in 2008. It was this meeting that inspired Annie and I to set up BUS. Continue reading
We are so grateful to Dr Graham Wallace for writing the attached article, which explains the immunological process that leads to Birdshot. Dr Wallace is a member of the Birdshot Research Network and is Senior Lecturer in Immunity and Infection at the University of Birmingham. For those of you who attended the Birdshot Day in March 2012, you will remember that he gave a fascinating talk on ‘The Science of Birdshot’. If you want to see his talk, we have posted it at:
Here is Dr Wallace’s article on ‘An Immunological Basis For Birdshot’
The major histocompatability complex (MHC) is found on chromosome 6 in humans, and contains several genes which are involved in the immune response. Of particular significance are the genes that encode the human leucocyte antigens (HLA) which are fundamental to the immune system. HLA can be separated into two families: class I (A, B and C) and class II (DR and DQ). As class II molecules are not implicated in Birdshot I will not mention them again in the report. Each individual has two copies of HLA-A, B, and C on all cells of the body; one from their mother and one from their father. It is because of this genetic transfer from parent to child, that HLA class I were identified originally as transplantation antigens that must be matched for a successful tissue graft. The reason for this is the function of HLA class I which can be separated into two mechanisms;
(1) HLA class I proteins present small pieces of proteins that have been broken up inside the cell on the surface and these are recognised by immune cells, called cytotoxic CD8 cells, which can kill other cells. This is particularly relevant for protection against viruses which enter human cells and replicate. Some virus proteins are broken down and presented by HLA class I. That virally infected cell can be eliminated and the virus destroyed.
(2) The second function of HLA class I is to protect normal cells from being eliminated by another group of cells called natural killer (NK) cells. NK cells are also cytotoxic but do not recognise protein particles presented by HLA class I, as CD8 cells do. Rather, expression of HLA class I on a cell is recognised by protein called killer immunoglobulin-like receptor (KIR) on the NK cell and this interaction sends a “do not kill” signal to the NK cell and it moves on to check other cells. This benefit of this system is that some viruses cause HLA class I molecules to be removed from the surface of an infected cell thereby preventing recognition of viral fragments by CD8 cells. However such down-regulation of HLA class I will now make these cells susceptible to elimination by NK cells.
As HLA class I is found constitutively on all cells in the body they are not eliminated by NK cells. Bw4 is a region found on several HLA-B molecules.
KIR belong to specific families encoded by genes on chromosome 19 in humans. However, combinations of KIR vary between individuals and different cells may express more than one KIR. Both the inhibiting (KIRL), and activating (KIRDS) can be found on the same cell and it is the complex interaction of these molecules that control NK cells activation. (Fig 1)
Figure 1 – inhibitory KIRL recognise HLA class I molecules on cells and inhibit killing. Activating ligands induced by challenge are recognised by KIRS molecules. The balance between these signal determines outcome.
The MHC class I molecule, HLA-A*29, is associated with Birdshot uveitis. KIR-HLA pairs implicated for weak inhibition such as KIR3DL1 + HLA-Bw4(T80)) in combination with activating KIR (KIR2DS2, KIR2DS3 and KIR2DS4) were found associated with increased risk in BCR HLA A*29 positive patients with BU. By comparison, association of strong inhibitory pairs such as KIR3DL1+HLA-Bw4(I80) in combination with KIR3DS1 was observed in HLA-A*29-negative controls. These results suggest that a profound effect of activating KIR (KIR2DS2/S3/S4) in the absence of strong inhibition may enhance the activation of natural killer cells and T-cell subsets against intraocular self-antigens, thereby contributing to pathogenesis of BCR.
To confirm the role of HLA-A2902 in the disease the gene inducing the protein was obtained from a patient with Birdshot and used to create a transgenic mouse. These animals did develop ocular disease that was similar to Birdshot, but not until 12 months of age confirming the effect of ageing on the condition.
Figure 2 – the reason why certain combinations of HLA and KIR are maintained is because they are useful at protecting against infections, but in combination with other gene polymorphisms this can lead to autoimmune disease.
The challenge in Birdshot as in many other forms of disease is to determine what the effect of the various combinations have at a functional level. ie do cells from patients with certain combinations “kill” less efficiently and what does this mean for the patients. It will also be necessary to analsye other genes for variants that may give an additive effect to the HLA:KIR combination and lead to disease.
BUS was recently invited to participate in a debate on ‘How Can We Improve Earlier Access to Medicines for Patients in the UK?’ The debate was set up by Les Halpin, a very inspirational man who founded EMPOWER: Access To Medicine following his diagnosis of Motor Neurone Disease and realising that there were few medications licensed for this disease and that if research was undertaken on new medications, it would take many months or even years before the medicine was available for use.
This debate was held at the King’s Fund in London and brought together a range of leading and influential individuals including:
▪ Lois Rogers, leading health journalist and contributor to publications including The Sunday Times, The Economist and New Statesman and consultant to the Department of Health and other government agencies
▪ Dr Richard Barker, Director of the Centre for Accelerating Medical Innovations, Oxford University and former head of the ABPI
▪ Yogi Amin, human rights and medical ethics lawyer, Irwin Mitchell
▪ Alastair Kent, Director of Genetic Alliance UK
▪ Professor Sir Peter Lachmann, Emeritus Sheila Joan Smith Professor of Immunology in the University of Cambridge and a fellow of Christ’s College
BUS has received a thank you letter for its input into the debate, which is copied below and gives information on how you can become involved in this campaign and how you can access the film of Les Halpin talking about the campaign:
Empower: Access to Medicine
I would like to personally thank you for attending the Empower: Access to Medicine debate at the King’s Fund last week. We appreciate your interest in and support for such an important subject.
I am very heartened by the response to this campaign. Whilst there are many separate discussions that are taking place on this issue, my main interest is in the voice of the patient which I believe has been least heard to date.
I am therefore delighted that patient advocacy groups from around the country have responded so positively. My key aim moving forward will be to support a unified patient voice so we can together deliver much needed change.
A longer and more comprehensive version of the film that was shown at the debate is now available online at www.accesstomedicine.co.uk and I would urge you to share this with colleagues and networks that may also be interested.
You can also join the conversation online through Twitter – find us on @empoweratm
The Empower team is now defining its campaign objectives as we continue to reach out to interested individuals and groups and we will keep you informed of our next steps.
In the meantime, if you have any questions or suggestions about the campaign, please contact Karen, James or Sarah at JBP on 0203 267 0074.
Founder, Empower: Access to Medicine
The Wall Street Journal published a really interesting article in August on how your eyes can reveal clues to your general health.
An ophthalmologist, Dr David Ingvoldstad from Midwest Eye Care in Omaha, Nebraska regularly alerts his patients to possible autoimmune diseases they may be at risk from or have, such as rheumatoid arthritis and lupus. He does this through their vision changes, or through the state of health of their eyes. He has even been able to monitor the progression of a patient’s diabetes through their eyes, and once alerted a patient to the fact that they had a brain tumour, based on the changes in their vision.
He is able to do this because the body’s systems are interconnected, and changes in the eye can reflect changes in the vascular, nervous and immune system.
The article suggests that, with regular monitoring, ophthalmologists can be the first to spot certain medical conditions and can ensure that patients receive early care and treatment.
We, with Birdshot, are regularly monitored! One benefit of having Birdshot.
Read the full article at:
We are thrilled to announce that tickets are now available for our first Winter Benefit – it promises to be a fun evening and a great excuse to get together, party and raise much-needed funds.
DATE: Saturday 3rd November
VENUE: The Rifles Club,52-56 Davies Street,London W1K
TICKETS: £80 each
The evening will commence at 7.30pm with a champagne & canapé reception, followed by a three course dinner with wine, and dancing until the early hours!
Fundraising activities during the night will include a silent auction and raffle. We are looking for companies to help sponsor the event and also for prizes, so if anyone has suggestions for either or if you would like to order tickets please contact either firstname.lastname@example.org or email@example.com
We look forward to seeing you there!
This website does exactly what it says – you can raise money for BUS every time you shop online and it won’t cost you anything, it’s that easy! Simply sign up at www.easyfundraising.org.uk and specify “Birdshot Uveitis Society” as the charity for which you are raising funds, then every time you make any purchase online you just need to do so via the easyfundraising website and the retailer will automatically make a donation to BUS. There is absolutely no cost to you, the site covers all of the major online retailers, and BUS benefits from a donation.
I recently booked the flights for a family holiday this way and we just got a donation of £17.85!
Please, if you do even a little shopping online, sign up today, we really do need your help!
The Medicines and Healthcare products Regulatory Agency (MHRA) is the agency that regulates all new medicines. They weigh up the risks and benefits of each new medicine, following the completion of phase III trials and then decide whether to license it or not. Some of us with Birdshot will know that we are unable to get some medications that may be licensed elsewhere (e.g. in the US) or that have been tested at phase III trials, but have to go through the sometimes lengthy procedure to be licensed.
The MHRA is now consulting on whether they should provide early access to medicines before they are formally licensed. The consultation period ends on 5 October, and if the MHRA goes ahead with this scheme, it may mean that those of us who have tried all the more traditional approaches to controlling our Birdshot without success can get hold of newer medications earlier.
There are a few provisos, of course! The scheme will be voluntary and limited to medicines that show a “significant advance in treatment in an area of unmet need”. The MHRA also expects to limit the scheme to only one or two medicines each year. Finally, the scheme will be limited to those medicines that have reached phase III trials (apart from exceptional cases – yet to be defined). If this scheme goes ahead, the MHRA will provide an opinion of the risks and benefits of the medicine on its web site to help clinicians and patients decide, and it would then be up to the funding body (your local clinical commissioning group made up of GPs in your area; or specialist commissioning group) to decide whether to fund the medicine or not.
So, even if the scheme is launched, there will still be hurdles to jump over, but at least it provides hope for those of us who are struggling to get hold of medicines on the NHS which are not licensed here.
It would be really, really helpful if our patient and professional members could give their comments to the MHRA
To read more about the proposed scheme, please click on the link below:
If you want to give your comment on this scheme, you can email firstname.lastname@example.org by 5 October 2012
The next meeting for Birdshot Friends in the London/SE area will be held on Saturday 9th June, from 10.30am – 1.00pm at St Thomas’s Hospital, Westminster Bridge Road, London SE1 7EH.
The meeting will take place in South Wing Lecture Theatre on the Ground Floor, near to the eye department. We might even go for lunch afterwards!
Joining us will be Professor Glen Jeffrey who has some new research to share with us and who is asking for our help – very exciting!!
There will also be some other guests on the day – watch this space!! – and plenty of opportunity to chat and catch up on all things Birdshot!
Everyone is welcome! If you are planning to come along please do e mail us at email@example.com
We look forward to seeing you there!
South East Team x