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Sarcoidosis: surface marker allows new diagnostic approaches
A team of scientists at the Helmholtz Zentrum München together with colleagues of the Ludwig Maximilians University Munich recently developed a new strategy to determine monocyte subsets involved in diseases. The results published in the journal ‘Blood’ could help facilitating the diagnosis of sarcoidosis and may improve the respective patient management.
Monocytes are white blood cells that are crucial to human immune defense. They are precursor cells of macrophages and dendritic cells and are circulating in the blood until they invade their respective target tissue where they defend the body against exogenous structures. So far, scientist categorized subtypes of monocytes only with regards to the surface markers CD14 and CD16* – however, this might change in the future.
Surface molecule as new marker
In the current study, the team headed by Prof. Loems Ziegler-Heitbrock was able to show that the analysis of an additional marker molecule called slan allows a more precise determination of monocyte subgroups. The results of the researchers show that this classification might also lead to a better understanding of certain diseases.
To this end Dr. Thomas Hofer and Dr. Marion Frankenberger, scientists of the Comprehensive Pneumology Center (CPC) at Helmholtz Zentrum München, analyzed blood samples of patients suffering from sarcoidosis. This disease, which often leads to damage of the patients’ lungs, is caused by a strong immune reaction and a concomitant formation of nodules in the tissue. The underlying mechanisms are still unclear but scientists are convinced that monocytes play a critical role. “Our data clearly indicate which subtype of the monocytes is involved in the disease”, explains Hofer. “In the patients’ blood we found significant numbers of monocytes, which were positive for CD16 and negative for slan.” According to Hofer, these cells might play a major role in sarcoidosis.
Also a role in brain disease
Moreover, in further experiments the scientist found that the marker slan might also serve to gain insights into a brain disease: “To test the predictive value of our new diagnostic tool, we also analyzed samples of patients suffering from HDLS**, a disease which leads to destruction of neurons of the brain”, said Frankenberger. “Our results show that a clearly definable subgroup of monocytes (CD16 positive/slan positive) was almost absent in the blood of these patients. Therefore we presume that these cells are important for normal brain function”, explains the Co-author.
“With this novel approach we now have a new diagnostic tool and we expect this to have an impact in many areas of medicine”, concludes principle investigator Ziegler-Heitbrock. “In the future we are planning to investigate whether slan might also lead to new insights with regards to other diseases.”
* The number of CD16 positive monocytes is increased in many infectious diseases. Since 2010 these proinflammatory cells can be subdivided according to cell surface markers: Classical monocytes (CD14++CD16−), Intermediate monocytes (CD14++CD16+) and Non-classical monocytes (CD14+CD16++). The results of the current study allow for a clear classification of these cells.
** HDLS stands for hereditary diffuse leukoencephalopathy with spheroids. This adult-onset disease affects the brain by degrading the myelin sheath of neurons and leads to the formation of so called spheroids. This leads to a progressive cognitive and motor dysfunction.
The study is the result of a co-operation of the Helmholtz researchers with the Department of Internal Medicine IV, Saarland University Medical Center, with the Asklepios Fachklinik in Muenchen-Gauting and with the Department of Neurology of the Ludwig Maximilians University in Munich.
Hofer, T. et al. (2015). Slan-defined subsets of CD16-positive Monocytes: Impact of granulomatous Inflammation and M-CSF-Receptor Mutation, Blood, DOI: 10.1182/blood-2015-06-651331
The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches to the prevention and therapy of major common diseases such as diabetes and lung disease. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. The Helmholtz Zentrum München is a partner in the German Center for Diabetes Research.
The Comprehensive Pneumology Center (CPC) is a joint research project of the Helmholtz Zentrum München, the Ludwig-Maximilians-Universität Clinic Complex and the Asklepios Fachkliniken München-Gauting. The CPC's objective is to conduct research on chronic lung diseases in order to develop new diagnosis and therapy strategies. The CPC maintains a focus on experimental pneumology with the investigation of cellular, molecular and immunological mechanisms involved in lung diseases. The CPC is a site of the Deutsches Zentrum für Lungenforschung (DZL).
Scientific contact at Helmholtz Zentrum München:
Dr. Thomas Hofer, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Comprehensive Pneumology Center, Ingolstädter Landstr. 1, 85764 Neuherberg - Phone +49 89 3187 1888 - E-mail