Researchers characterise rare immune disorder
18 February 2011
A study of patients in Newcastle - funded by the blood cancer charity Leukaemia & Lymphoma Research, the MRC and the Wellcome Trust - identified four individuals with what the scientists have labelled 'DCML deficiency syndrome'. By looking at the different populations of immune cells in these patients, they found that the determining feature of the syndrome is that they have almost no dendritic cells or monocytes - vital cells of the immune system that originate in the bone marrow and help to fight infection.
The research was published in the prestigious 'Journal of Experimental Medicine' on 14 February; it is the first time that dendritic cell deficiency has been described in humans. Without treatment, patients may die of lung disease, leukaemia or infections. This can be prevented by a bone marrow stem cell transplant to correct the body's immune system and prevent the risk of leukaemia.
Stacey Sheppard, 23, from Sunderland, was among the first patients in the world to be diagnosed with and treated for this syndrome. She was rushed to Newcastle's Freeman Hospital at the end of 2009 with breathing difficulties and was eventually diagnosed with pulmonary alveolar proteinosis, a rare lung problem caused by the deficiency syndrome. Having spent months in hospital with continual lung infections, Stacey eventually became oxygen dependent and had to sleep with the aid of a ventilator. Stacey said of her condition at the time: "I was so breathless that I could hardly move. Simple little things became impossible, my weight dropped and I had no quality of life."
Tests of Stacey's bone marrow taken in July 2010 revealed that she had DCML deficiency, offering doctors a chance to tackle what could be the root cause of her symptoms. She underwent a bone marrow transplant three months later, in an attempt to replace the missing cells of her immune system and repair her lungs.
Stacey said: "I was told that the transplant was not guaranteed to be successful and that I may not survive, but if I didn't have it I was given a life expectancy of one year. The transplant has quite simply given me my life back - I can now walk short distances, I still require oxygen but it's considerably reduced and I no longer need a ventilator at night time. I've got a three-year-old girl so it's been wonderful to be home with her and able to do activities with her that I've missed out on. The difference is incredible."
Professor Matthew Collin, Stacey's consultant and the scientist who led the research at the Institute of Cellular Medicine at Newcastle University, said: "The identification of this immune deficiency syndrome is important because it gave us the confidence to perform a bone marrow stem cell transplant and offer a real chance of a cure. It is also important for Stacey to remove the risk of leukaemia and other cancers in the same way that bone marrow transplantation is already used to save the lives of many people affected by blood cancers."
Stacey's father died from lung problems at the age of 35. His own father (Stacey's grandfather) had died of leukaemia in his 30s, as had his father's sister. Although this study does not solve the genetic basis of the disorder, the insight it brings offers the hope of treatment to the future generations of families that are affected.
Dr David Grant, Scientific Director at Leukaemia & Lymphoma Research, said: "Identifying this new hereditary syndrome will allow us to take action early on and prevent people from developing leukaemia, a blood cancer from which up to half of all patients still do not survive."
Image: An immature dendritic cell migrating over a fibronectin substrate (the actin-rich podosomes that mediate this migration show up as red dots). Dendritic cells are immune surveillance cells that migrate around the body, presenting antigens to other cells of the immune system. Credit: Professor Gareth Jones, Wellcome Images.
Reference
Bigley V et al. (2011) The human syndrome of dendritic cell, monocyte, B, and NK lymphoid deficiency. Journal of Experimental Medicine, 208: 227-34.
