Evaluation of a tryptase depletion index for better pathologic identification of mast cell activation syndrome

Tomasz Zienkiewicz; Jürgen Homann; Martin Mücke; Holger Seidel; Hans-Jörg Hertfelder; Leonard B. Weinstock; Lawrence B. Afrin; Gerhard J. Molderings

doi:10.1055/a-1833-9226

Zeitschrift für Gastroenterologie, Inhaltsverzeichnis

Z Gastroenterol 2023; 61(03): 268-274
DOI: 10.1055/a-1833-9226

Originalarbeit

Evaluation of a tryptase depletion index for better pathologic identification of mast cell activation syndrome

Evaluierung eines Tryptase-Freisetzungsindex zur verbesserten pathologischen Identifizierung des Mastzellaktivierungssyndroms

Autor*innen

Tomasz Zienkiewicz

¹Institute of Pathology Bonn-Duisdorf, Bonn, Germany
Jürgen Homann

²Division of Internal Medicine, Gemeinschaftskrankenhaus Bonn, Bonn, Germany
Martin Mücke

³Institute for Digitalization in General Practice and Center for Rare Diseases Aachen (ZSEA), University Hospital Aachen, Aachen, Germany (Ringgold ID: RIN39058)
Holger Seidel

⁴Center for Bleeding Disorders and Transfusion Medicine (CBT), Bonn, Germany
Hans-Jörg Hertfelder

⁴Center for Bleeding Disorders and Transfusion Medicine (CBT), Bonn, Germany
Leonard B. Weinstock

⁵Departments of Medicine, Missouri Baptist Medical Center and Washington University School of Medicine, St. Louis, MO, United States
Lawrence B. Afrin

⁶AIM Center for Personalized Medicine, Purchase, NY, United States
Gerhard J. Molderings

⁷Institute of Human Genetics, University of Bonn, Bonn, Germany

Abstract

Background Laboratory evidence supporting diagnosis of the prevalent condition of mast cell activation syndrome (MCAS) currently includes elevated levels in blood or urine of mediators relatively specific to mast cells (MCs) and/or increased numbers of MCs in luminal gastrointestinal (GI) tract tissues. However, identification of elevated mediators is technically challenging and expensive, and controversy persists regarding the normal ranges of numbers/counts of MCs in various GI tract segments, let alone challenges in determining how many of the visualized MCs are activated. To aid diagnosis of MCAS, we developed a potential new approach for the pathologist to identify the extent of GI tract MC activation easily and inexpensively.

Participants and Methods Visualization of MCs in gastrointestinal biopsies from 251 patients vs. 95 controls using antibodies against CD117 and tryptase; MC counting per mm²; calculation of the difference between the CD117-positive MCs (identifying all MCs) vs. tryptase-positive MCs (identifying non-activated tryptase-containing MCs), which we define as the tryptase depletion index (TDI).

Results Mean total MC counts did not differ significantly between patients and controls, but mean TDIs differed significantly. Non-overlapping confidence intervals at the 99.9% level identified cut-offs of TDIs between patients vs. controls of 26, 45 and 32 MCs/mm² in gastric antrum, duodenum, and colon, respectively.

Conclusions The TDI may discriminate between MCAS patients vs. controls. If this preliminary work can be independently confirmed, the TDI may become a useful additional minor diagnostic criterion for MCAS.

Zusammenfassung

Hintergrund Laborwerte, die die Diagnose des häufig auftretenden Mastzellaktivierungssyndroms (MCAS) stützen, umfassen derzeit erhöhte Blut- oder Urinspiegel von Mediatoren, die relativ spezifisch für Mastzellen (MCs) sind und/oder eine erhöhte Anzahl von MCs in der Mukosa des Gastrointestinaltrakts (GIT). Der Nachweis erhöhter Mediatorspiegel ist jedoch technisch anspruchsvoll und teuer, und die Angaben für die normale Mastzelldichte in den verschiedenen GIT-Segmenten sind umstritten, ganz abgesehen von den Schwierigkeiten des Nachweises, wie viele der visualisierten MCs aktiviert sind. Um die Diagnose einer MCAS zu stützen, haben wir einen potenziellen neuen Ansatz für die pathologische Untersuchung entwickelt, der eine einfache und preiswerte Bestimmung der MC-Aktivität im GIT erlaubt.

Studienteilnehmer und Methodik Visualisierung der MCs in gastrointestinalen Biopsien von 251 MCAS-Patienten und 95 Kontrollpersonen mittels CD117- und Tryptase-Antikörper; Zellzählung pro mm²; Berechnung der Differenz der Mastzellzahl zwischen CD117- (Anfärbung aller MCs) und Tryptase-positiven MCs (Nachweis nicht aktivierter tryptasehaltiger MCs), die wir als Tryptasefreisetzungsindex (TDI) bezeichnen.

Ergebnisse Die mittleren Mastzelldichten der Patienten unterschieden sich nicht signifikant von denen der Kontrollgruppe, wohingegen sich die Mittelwerte der TDIs signifikant unterschieden. Die nicht überlappenden Konfidenzintervalle auf dem 99,9% Niveau erlaubten eine Definition von Grenzwerten für die TDIs zur Unterscheidung von Patienten und Kontrollpersonen von 26, 45 und 32 Mastzellen/mm² im Magenantrum, Duodenum bzw. Kolon.

Schlussfolgerungen Der TDI erlaubt eine Unterscheidung zwischen MCAS-Patienten und Kontrollpersonen. Wenn diese erstmalige Beobachtung in Studien anderer Untersuchergruppen bestätigt werden kann, könnte der TDI in der Diagnostik des MCAS ein nützliches zusätzliches Nebendiagnosekriterium werden.

Schlüsselwörter

Mastzellaktivierungssyndrom - Mastzelldichte - Mastzellaktivität - diagnostische Kriterien - CD117-Antikörperfärbung - Tryptase-Antikörperfärbung - Tryptasefreisetzungsindex

Keywords

mast cell activation syndrome - mast cell density - mast cell activation - diagnostic criteria - CD117-antibody staining - tryptase-antibody staining - tryptase depletion index

Volltext

Referenzen

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