We have written many posts on helminthic therapy (worms) and they seem to be engendering a lot of interest in the research and scientific communities. Continue reading
We have posted before about curcumin and the possible benefits to our eyes.
A recent study at the Department of Cardiology, Union Hospital, Huazhong University of Science and Technology, China has looked at curcumin for autoimmune diseases. Continue reading
Qingkailing is a chinese medicine formula which has been used for cerebrovascular diseases and some inflammatory diseases including uveitis. At one stage, about five years ago, there was some work in the US looking at the possibilities of using this for uveitis. It is given as an injection and has a number of ingredients including some traditional roots and flowers.
There has been a recent trial at Shandong University of Traditional Medicine Eye Hospital where qingkailing was injected into rats with autoimmune uveitis (Birdshot is an autoimmune uveitis). It was found that it could offer immunomodulatory effects.
If this is the case (it will need to be trialled on people too), it could be a possible alternative to the rather toxic systemic medications we currently have to take.
Read the full story at
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.
The Birdshot Uveitis Society’s unique Christmas card, designed for us by Birdshot Uveitis Society member David Bethell are now available for people to purchase. All profit from the sale of these cards will support the work of the Birdshot Uveitis Society.
Cards measure 150mm x 150mm and are printed on a quality card. They come in packs of 10 with white envelopes and are priced at £3.95 per pack. The greeting inside the card is “Merry Christmas and a Happy New Year”.
To order your cards:
Please simply click add to cart button below, type in the number of packs of cards you wish to purchase, click update and follow the instructions using either a credit card or Pay Pal to pay for your order.
If your order is for more than 6 packs please order by emailing email@example.com and we will send you a Pay Pal invoice for you to pay which will include the higher rate of postage and packing of £4.95. Also if you wish to have cards sent to you overseas please email us with your request and we will invoice you with the correct amount to pay via Pay Pal and will dispatch them to you once we have received payment.
You may also order via the post by sending your order and cheque made payable to Birdshot Uveitis Society to BUS Box 64996. London SW20 2BL.
Postage and packing rates
|Up to £25||£25.01 & over|
|Eire & Europe||40% of purchase price, minimum £4|
|Rest of World||40% of purchase price, minimum £4|
Last date for UK orders to allow posting to you before Christmas: 13-Dec-12 Purchases after this date are delivered at your own risk of late delivery
If you want us to send cards overseas, please make sure you allow enough time for delivery.
A single-centre pilot study is being undertaken in the United States to investigate the safety, tolerability and potential efficacy of subcutaneous injections of ustekinumab for uveitis. The hope is, that if this drug works, it will have fewer side effects than the current protocol of steroids and immunosuppressants.
Ustekinumab is a human monoclonal antibody and is classed as a ‘biologic’ drug. It is currently used for people with psoriasis and some other conditions.
The study is due to complete in June 2013. If this drug is effective, we will have yet another potential drug for Birdshot, for those people who find it hard to tolerate steroids and immunosuppressants.
The Institute of Immunology and Infection Research at University of Edinburgh has published a paper on Helminth (worm) infections and host immune regulation. It looks at countries and areas where helminth parasites are endemic (i.e. many people carry these worms all their lives) and note that in these countries, there is a very low incidence of autoimmune diseases and allergies. This suggests that the helminth parasites may protect against your immune system becoming disregulated.
The paper points out that there is now much interest in investigating helminths as a therapy, in both laboratory models and in human trials. They believe that understanding and exploiting the way these parasites work are likely to highlight new strategies to control both infectious and immunological diseases.
See the full text at:
Two US filmmakers have produced a documentary on Hermansky-Pudlak syndrome (HPS), a rare disease. This film highlights the issues faced by all of us with rare diseases.
Like Birdshot, very few doctors have heard of HPS, and no-one knows how many people have it. Getting diagnosed is difficult, and finding some-one else with the syndrome is difficult, so it is a lonely path people tread. They also point out that there are no disease specific medications (just like for Birdshot). We Birdshotters at least have an organisation (BUS) that lets us connect with other Birdshotters!
The film points out that whilst each rare disease is uncommon, if you take all rare diseases together, they are very common. It also explores the way that patients, once diagnosed, connect with others. They highlight a similar development to BUS for each of the rare diseases, and how the internet has helped in this.
The most interesting part of this film follows a parent of a patient with HPS as she tries to find other patients to participate in a clinical trial to test a new drug.
It is a really moving film. To see the full article go to:
The Department of Ophthalmology at University Vita-Salute in Milan, Italy has published a paper on their experience of treating difficult, uncontrolled and severe cases of noninfectious posterior uveitis (Birdshot is a noninfectious posterior uveitis) with dexamethasone intravitreal implants on top of systemic steroids. They found that, of the 12 patients they studied, all had decreased uveitis activity, increased visual acuity and reduction in the macular thickness after 9 months. Three patients were able to reduce their steroids. Only 3 of the eyes had an increase in intraocular pressure. Their conclusion is that dexamethasone may be a promising additional treatment for patients with sever posterior noninfectious uveitis which does not respond to immunosuppressants.
See the full text at
Last week we sent out a very short follow-up quality of life questionnaire to participants of our 1st questionnaire who kindly gave us their email address to allow us to follow-up.
We’d really like to see how things may have changed for you since undertaking the 1st survey. We do hope that you will all complete this as soon as possible as it will provide helpful data to supplement the original data .
If you have not received the email with the link to the survey and you think you should have, please get in touch with me at firstname.lastname@example.org so that I can resend the link to you.
Many thanks to all who have already completed it. We do appreciate your continued help with this useful research.