Clonal mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. diseases such as systemic mastocytosis (SM) may be more common among patients with anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis. than previously recognized, according to a screening analysis published recently in The Journal of Allergy and Clinical Immunology.
Clonal mast cell diseases are a group of disorders where a disease originates from a single mutated mast cell. They are typically driven by a KIT D816V mutation and cause abnormal mast cell growth and activation.
About 5% of patients with anaphylaxis have been estimated to have underlying clonal mast cell diseaseMast cell disease A group of conditions in which mast cells behave abnormally by building up in excess, releasing chemicals too easily or both. Includes mastocytosis, mast cell activation syndrome and hereditary alpha-tryptasemia., most commonly bone marrow mastocytosis or monoclonal mast cell activation syndrome.
In contrast, of the study patients with anaphylaxis who received thorough bone marrow testing, nearly three-quarters — 29 out of 40 — were found to have clonal mast cell disease.
In addition to the anaphylaxis findings, the study also found that the REMA score (short for Red Española de Mastocitosis, or Spanish Network on MastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults.) was more sensitive than blood-based KIT D816V mutation testing in identifying patients with clonal mast cell disease. The score uses clinical features and baseline serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. levels to estimate the likelihood of clonal mast cell disease and can help determine who may need additional testing.
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The study’s investigators evaluated 57 adults with anaphylaxis at the Institute of Mastocytosis Studies of Castilla-La Mancha in Spain. Hereditary alpha-tryptasemia — a genetic trait that raises the risk of anaphylaxis — was identified in 19 of the patients (33.3%). The most common anaphylaxis triggers were insects, drugs and food. A REMA score of at least 2, indicating a high probability of clonal mast cell disease, occurred in 38 patients (67%).
Read more about SM causes and risk factors
Among 40 patients who underwent bone marrow assessment, 29 had clonal mast cell disease, including 22 with bone marrow mastocytosisBone marrow mastocytosis A subtype of indolent SM that occurs when the excess mast cells accumulate in the bone marrow, but not the skin or other organs. and seven with monoclonal mast cell activationMast cell activation Describes when mast cells release histamine and other mediators into the blood stream in response to an allergen or other trigger. This leads to symptoms like fatigue, rash and, in severe cases, anaphylaxis. syndrome. No cases of indolent SMIndolent SM A subtype of nonadvanced SM caused by the abnormal accumulation of mast cells in the bone marrow and other organs. Indolent SM accounts for around 90% of SM cases. were identified. The minimum confirmed clonal mast cell disease prevalence among all screened patients was 51%, although only a subset underwent bone marrow confirmation. Investigators cautioned that the referral center population may have been enriched for patients with severe or recurrent anaphylaxis.
The REMA score was the most effective of three methods at identifying people with clonal mast cell disease, correctly detecting 83% of those who had the disease, compared with 34% for an allele-specific oligonucleotide quantitative PCR test and 10% for a droplet digital PCR test. KIT D816V was undetectable in peripheral blood by either assay in 12 of the 22 patients with bone marrow mastocytosis. In seven of those patients, the mutation was detected only after mast cells were purified from bone marrow samples, underscoring why negative blood testing does not necessarily exclude clonal mast cell disease or SM.
For patients, the findings could mean fewer missed diagnoses and more appropriate follow-up after unexplained or severe anaphylaxis.
“Inability to detect KIT D816V in [peripheral blood] with [droplet digital] PCR and [allele-specific oligonucleotide quantitative PCR] should not be interpreted as absence of cMCD [clonal mast cell disease],” the investigators wrote.
The authors noted that more sensitive blood tests and continued use of clinical tools such as the REMA score could help determine which patients need more extensive evaluation. This may become increasingly important as targeted treatments such as avapritinib are developed for KIT D816V-associated disease.
