Diagnosis of Primary Mast Cell Disorders in Anaphylaxis: Value of KIT D816V in Peripheral Blood

Puysseleyr, Leander P. De; Ebo, Didier G.; Elst, Jessy; Faber, Margaretha A.; Poorten, Marie-Line M. van der; Gasse, Athina L. Van; Bridts, Chris H.; Mertens, Christel; Houdt, Michel van; Hagendorens, Margo M.; Verlinden, Anke; Vermeulen, Katrien; Maes, Marie-Berthe; Berneman, Zwi; Sabato, Vito

doi:10.1016/j.jaip.2021.04.062

Cited by 9 publications

(20 citation statements)

References 34 publications

(56 reference statements)

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“…One patient presented with MIS and had a positive KIT DV816V mutation in PB but refused the BM biopsy. This patient was included in the CMCD patients without anaphylaxis group because the adult onset of MIS and the presence of KIT D816V mutation in peripheral blood (PB) (24). Three of the 27 patients had no signs of a CMCD after full diagnostic work-up but had only an elevated bST.…”

Section: Methods Study Populationmentioning

confidence: 99%

“…KIT D816V mutation in PB and BM was determined, as described earlier (24), using digital droplet PCR (Bio-Rad, Hercules, USA). Quantification of the KIT D816V allele burden in the BM cells was available in 14 patients with a CMCD with wasp venom anaphylaxis and 13 patients with a CMCD patients without anaphylaxis with a sensitivity of at least 0.01% positive alleles.…”

Section: Baseline Serum Tryptase Allergy Work-up and Kit D816v Mutationmentioning

confidence: 99%

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Overexpression of FcεRI on Bone Marrow Mast Cells, but Not MRGPRX2, in Clonal Mast Cell Disorders With Wasp Venom Anaphylaxis

et al. 2022

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BackgroundUncertainties remain about the molecular mechanisms governing clonal mast cell disorders (CMCD) and anaphylaxis.ObjectiveThis study aims at comparing the burden, phenotype and behavior of mast cells (MCs) and basophils in patients with CMCD with wasp venom anaphylaxis (CMCD/WVA+), CMCD patients without anaphylaxis (CMCD/ANA-), patients with an elevated baseline serum tryptase (EBST), patients with wasp venom anaphylaxis without CMCD (WVA+) and patients with a non-mast cell haematological pathology (NMHP).MethodsThis study included 20 patients with CMCD/WVA+, 24 with CMCD/ANA-, 19 with WVA+, 6 with EBST and 5 with NMHP. We immunophenotyped MCs and basophils and compared baseline serum tryptase (bST) and both total and venom specific IgE in the different groups. For basophil studies, 13 healthy controls were also included.ResultsHigher levels of bST were found in CMCD patients with wasp venom anaphylaxis, CMCD patients without anaphylaxis and EBST patients. Total IgE levels were highest in patients with wasp venom anaphylaxis with and without CMCD. Bone marrow MCs of patients with CMCD showed lower CD117 expression and higher expression of CD45, CD203c, CD63, CD300a and FcεRI. Within the CMCD population, patients with wasp venom anaphylaxis showed a higher expression of FcεRI as compared to patients without anaphylaxis. Expression of MRGPRX2 on MCs did not differ between the study populations. Basophils are phenotypically and functionally comparable between the different patient populations.ConclusionPatients with CMCD show an elevated burden of aberrant activated MCs with a significant overexpression of FcεRI in patients with a wasp venom anaphylaxis.

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Section: Methods Study Populationmentioning

confidence: 99%

Section: Baseline Serum Tryptase Allergy Work-up and Kit D816v Mutationmentioning

confidence: 99%

Overexpression of FcεRI on Bone Marrow Mast Cells, but Not MRGPRX2, in Clonal Mast Cell Disorders With Wasp Venom Anaphylaxis

et al. 2022

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“…The difference might be explained by the inclusion of only one MMAS patient in the Danish cohort, 11 while sensitivity in the current and Belgian cohort was particularly low in MMAS patients. 12 The reduced sensitivity in MMAS patients could reflect a lower mast cell burden and/or lower multilineage KIT Lastly, this study evaluated the frequency of HAT and its potential added value in detecting CMD in this subpopulation. Although numbers were too low to draw conclusions, frequency in the normal bsT range is low 15,22 and HAT was found in both CMD and non-CMD patients.…”

Section: Discussionmentioning

confidence: 99%

“…Our findings on the KIT assay in PB confirmed findings of previous studies regarding the high specificity (100%). 11,12 Therefore it could have added value as additional screening method in patients with a low REMA score. Here and in previous reports several patients with low REMA scores who tested positive for KIT in PB are described.…”

Section: Discussionmentioning

confidence: 99%

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Detection of clonal mast cell disease in wasp venom allergic patients with normal tryptase

Onnes

Alheraky

Nawijn

et al. 2022

Clinical & Translational All

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Background: Clonal mast cell disease (CMD) is an underlying aggravating condition in wasp venom allergy (WVA) which requires a different treatment strategy. CMD is increasingly recognized in patients with normal basal serum tryptase (bsT). However, methods to identify at risk patients have not yet been assessed in large cohorts of WVA patients with normal bsT. Methods: This retrospective study evaluated the reliability of the REMA score in detecting CMD in a cohort of grade IV WVA patients with normal bsT and assessed the added value of other clinical parameters, KIT D816V mutation analysis in peripheral blood (PB) and the diagnosis of hereditary alpha tryptasemia (HAT). All patients had a conclusive bone marrow evaluation that demonstrated or excluded underlying CMD.Results: In total 35 CMD and 96 non-CMD patients were included. REMA score had a sensitivity of 72% (95% CI 56%-88%) and specificity of 79% (95% CI 70%-87%) in this cohort. Loss of consciousness during systemic reaction and bsT between 6.3 and 11.4 ng/ml were additional parameters independently associated with CMD.Sensitivity of KIT in PB was relatively low, 56% (95% CI 36%-75%), but had added value as screening method in patients with a low REMA score due to 100% specificity. Conclusion:The REMA score is a relatively reliable method to detect patients at risk of CMD among WVA patients with normal bsT. KIT mutation analysis in PB could serve as additional screening method in patients with low REMA scores. K E Y W O R D Sinsect venom, KIT D816V analysis in peripheral blood, mastocytosis, REMA score, tryptaseThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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IgE-mediated anaphylaxis to methylprednisolone succinate in a patient with indolent systemic mastocytosis

Mieghem

Beyens

Gasse

et al. 2022

Allergology International

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Diagnosis of Primary Mast Cell Disorders in Anaphylaxis: Value of KIT D816V in Peripheral Blood

Cited by 9 publications

References 34 publications

Overexpression of FcεRI on Bone Marrow Mast Cells, but Not MRGPRX2, in Clonal Mast Cell Disorders With Wasp Venom Anaphylaxis

Overexpression of FcεRI on Bone Marrow Mast Cells, but Not MRGPRX2, in Clonal Mast Cell Disorders With Wasp Venom Anaphylaxis

Detection of clonal mast cell disease in wasp venom allergic patients with normal tryptase

IgE-mediated anaphylaxis to methylprednisolone succinate in a patient with indolent systemic mastocytosis

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