Erstarrt – im Bann der Kälte (Agglutinine)

Zusammenfassung

Die Kälteagglutininkrankheit (CAD) ist klassifiziert [1] als eine eigene Entität und steht in Abgrenzung zum Lymphoplasmozytischen Lymphom (LPL) oder IgM MGUS (Monoklonale Gammopathie unklarer Signifikanz). Grundlage ist eine lymphoproliferative Erkrankung mit einem aberranten B-Zellklon [2, 3].

Insgesamt ist die primäre CAD selten, in der Regel liegt ein sogenanntes sekundäres CAS (Cold Agglutinin Syndrome) im Rahmen von Infektionen (z. B. durch Mycoplasmen, Lues, EBV und Hepatitis) und insbesondere bei Lymphomerkrankungen vor [4–8].

Es ist von entscheidender Bedeutung, ein CAS auszuschließen, da hieraus ein anderes therapeutisches Vorgehen folgt [9]. Die Diagnostik beinhaltet eine klare immunhämatologische Darstellung der kältewirksamen IgM Auto-Antikörper (>90,1% IgM, 4,5% IgG sowie gemischt 2,8%) [10, 11]. Die Schwierigkeit ist hierbei, eine suffiziente Präanalytik zu gewährleisten, da bei Routine-Einsendungen nur schwer hämolytisches Material zur Verfügung steht, aus dem ggf. kein Antikörper mehr detektiert werden kann.

Als klinische Manifestation stehen vor allem eine Komplement-vermittelte Autoimmunhämolyse bei unter 37°C Körpertemperatur sowie thromboembolische Ereignisse im Vordergrund. Seit 2022 ist Sutimlimab (Enjaymo) von der EMA (European Medicines Agency) für die Behandlung der CAD zugelassen [12, 13].

Abstract

Cold agglutinin disease (CAD) is recognized as a distinct clinical and pathological entity, clearly differentiated from lymphoplasmacytic lymphoma (LPL) and IgM monoclonal gammopathy of undetermined significance (MGUS) [1]. It is characterized by an underlying lymphoproliferative disorder involving an aberrant B-cell clone [2, 3].

Primary CAD is a rare condition. More commonly, secondary cold agglutinin syndrome (CAS) is observed, typically in association with infections (e. g., Mycoplasma pneumoniae, Syphilis, Epstein-Barr virus, Hepatitis) or as a secondary manifestation of lymphoproliferative malignancies [4–8]. Differentiating CAD from CAS is crucial, as the two entities necessitate distinct therapeutic strategies [9]. Diagnostic work-up includes immunohematological identification of cold-reactive autoantibodies, predominantly of the IgM class (>90.1% IgM, 4.5% IgG, and 2.8% mixed types) [10, 11]. A major diagnostic challenge lies in ensuring adequate pre-analytical conditions, as routine specimens often exhibit strong hemolysis, potentially compromising antibody detection.

Clinically, CAD primarily manifests as complement-mediated autoimmune hemolytic anemia at temperatures below 37°C, frequently accompanied by thromboembolic complications. Since 2022, the monoclonal antibody Sutimlimab (Enjaymo) has been approved by the European Medicines Agency (EMA) for the treatment of CAD [12, 13].

Schlüsselwörter

Kälteagglutininkrankheit - Autoimmunhämolytische Anämie - Komplementinhibitor - Lymphoproliferative Neoplasie - Sutimlimab

Keywords

Cold agglutinin disease - Autoimmune hemolytic anemia - Complement inhibitor - Lymphoproliferative disease - Sutimlimab

Publication History

Article published online:
12 August 2025

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