In the delicate balance that allows our immune systems to function, something can tip the scales. In haemophagocytic lymphohistiocytosis (HLH), for example, it can happen that macrophages – the “scavenger” cells with the task of eliminating infected cells – are activated in an uncontrolled way, and begin to eliminate healthy cells too, generating hyper-inflammation that involves the whole organism and that in the absence of therapy can lead to death in a few weeks. About two children per 100,000 are affected by HLH, although very few cases of HLH are also described in adolescents and adults. Precisely because of this very low incidence it is considered an ultra-rare disease, and difficult to recognize: in part because, especially in the initial stages, its symptoms are not characteristic, and traditional laboratory tests are not able to identify it. Second, because HLH can often be confused with other autoinflammatory diseases. Today, however, the diagnosis is easier, thanks to a simple laboratory test that allows not only to specifically identify the disease, but also to predict its severity. The credit goes to the researchers of the Bambino Gesù Pediatric Hospital in Rome led by Fabrizio De Benedetti, head of the Hospital’s Rheumatology Unit, who published on Blood the results of their study.
A blood sample is enough
In particular, the sciemziati have focused on one of the two forms in which HLH can occur: there is in fact a primary, or familial form, which has a genetic cause, and a secondary form, which can derive from previous pathologies, such as infections. viral, cancers, metabolic diseases such as diabetes, immunodeficiencies, rheumatic or autoinflammatory diseases. The survey therefore turned to the latter form. The researchers took blood samples from 99 pediatric patients, about half of whom had secondary HLH, specifically examining their peripheral blood cells. Here, thanks to techniques of flow cytometry or flow cytometry – a laboratory technique thanks to which it is possible to obtain important data of the cell, such as size, vitality, complexity, etc. – the researchers have shown that in the blood of children affected by Secondary HLH there is a markedly higher number of activated T lymphocytes than in people with other autoinflammatory diseases, such as those with systemic juvenile idiopathic arthritis. This factor is already useful to more easily distinguish the different diseases. But the researchers went one step further: They identified a particular subpopulation of T lymphocytes (called CD4dimCD8 +) that, when present in high quantities, is associated with a more severe form of secondary HLH. In this sense, once the disease has been identified, it is also possible to predict its evolution.
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From the laboratory to the patient’s bed
«One of the most important aspects of the results obtained with this study – explains Dr. Giusi Prencipe, medical biotechnologist of the Bambino Gesù and coordinator of the study – is the immediate translation. In other words, it is possible, as we are already doing at our hospital, to immediately transfer the results into clinical practice for the benefit of children and their families “. Thanks to the researchers’ discovery, therefore, today a small blood sample and the use of flow cytometry are enough to diagnose the disease and its evolution with great reliability and in a very short time. And this allows you to quickly start the most appropriate treatments and thus improve the prognosis.
HLH, clinical news is coming
Currently the therapy consists of a transplantation of hematopoietic stem cells, an intervention which however must be anticipated by a medical therapy that aims to control the uncontrolled inflammatory response typical of the disease. For this aspect, new therapeutic possibilities have recently been available thanks to biological drugs. One of these is the monoclonal antibody emapalumab, directed against a molecule (interferon-gamma) that plays a key role in regulating the immune response and that is produced in excess in patients with HLH. Emapalumab has been successfully tested at the Hospital of the Capital, first on the primary form and, more recently, on the secondary form of HLH. In the first trial, the drug was able to block the hyper-inflammation and control the acute characteristics of the disease in over 60% of cases. The results of the latest trial will instead be previewed at the next European rheumatology congress EULAR 2022, which will be held from 1 to 4 June in Copenhagen, Denmark.
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