Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for Therapy
The last 2 decades have seen great progress in understanding the pathogenesis of cold agglutinin disease (CAD) and development of effective therapies. Cold agglutinins can cause hemolytic anemia as well as peripheral circulatory symptoms such as acrocyanosis. We distinguish CAD, a well-defined clini...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Hemato |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-6357/3/4/40 |
| _version_ | 1797457402685030400 |
|---|---|
| author | Sigbjørn Berentsen Shirley D’Sa Ulla Randen Agnieszka Małecka Josephine M. I. Vos |
| author_facet | Sigbjørn Berentsen Shirley D’Sa Ulla Randen Agnieszka Małecka Josephine M. I. Vos |
| author_sort | Sigbjørn Berentsen |
| collection | DOAJ |
| description | The last 2 decades have seen great progress in understanding the pathogenesis of cold agglutinin disease (CAD) and development of effective therapies. Cold agglutinins can cause hemolytic anemia as well as peripheral circulatory symptoms such as acrocyanosis. We distinguish CAD, a well-defined clinicopathologic entity, from secondary cold agglutinin syndrome. This review addresses the histopathologic, immune phenotypic, and molecular features that allow CAD to be classified as a distinct clonal lymphoproliferative disorder of the bone marrow, recently recognized in the WHO classification. We discuss recent data on the possible overlap or distinction between CAD and Waldenström’s macroglobulinemia. Two major steps in the pathogenesis of CAD are identified: clonal B-cell lymphoproliferation (leading to monoclonal IgM production) and complement-mediated hemolysis. Each of these steps constitutes a target for treatment. Established as well as novel and experimental therapies are reviewed. |
| first_indexed | 2024-03-09T16:21:40Z |
| format | Article |
| id | doaj.art-5cd89b739fbe4aef947c9a3f6fbd6fa5 |
| institution | Directory Open Access Journal |
| issn | 2673-6357 |
| language | English |
| last_indexed | 2024-03-09T16:21:40Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Hemato |
| spelling | doaj.art-5cd89b739fbe4aef947c9a3f6fbd6fa52023-11-24T15:12:39ZengMDPI AGHemato2673-63572022-09-013457459410.3390/hemato3040040Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for TherapySigbjørn Berentsen0Shirley D’Sa1Ulla Randen2Agnieszka Małecka3Josephine M. I. Vos4Department of Research and Innovation, Haugesund Hospital, Helse Fonna Hospital Trust, NO-5504 Haugesund, NorwayUCLH Centre for Waldenström and Associated Conditions, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UKDepartment of Pathology, Akershus University Hospital, NO-1478 Nordbyhagen, NorwayDepartment of Haematology and Department of Pathology, Oslo University Hospital, NO-0318 Oslo, NorwayDepartment of Hematology, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsThe last 2 decades have seen great progress in understanding the pathogenesis of cold agglutinin disease (CAD) and development of effective therapies. Cold agglutinins can cause hemolytic anemia as well as peripheral circulatory symptoms such as acrocyanosis. We distinguish CAD, a well-defined clinicopathologic entity, from secondary cold agglutinin syndrome. This review addresses the histopathologic, immune phenotypic, and molecular features that allow CAD to be classified as a distinct clonal lymphoproliferative disorder of the bone marrow, recently recognized in the WHO classification. We discuss recent data on the possible overlap or distinction between CAD and Waldenström’s macroglobulinemia. Two major steps in the pathogenesis of CAD are identified: clonal B-cell lymphoproliferation (leading to monoclonal IgM production) and complement-mediated hemolysis. Each of these steps constitutes a target for treatment. Established as well as novel and experimental therapies are reviewed.https://www.mdpi.com/2673-6357/3/4/40cold agglutinin diseaseautoimmune hemolytic anemialymphoproliferativemonoclonal gammopathyWaldenström’s macroglobulinemiacomplement |
| spellingShingle | Sigbjørn Berentsen Shirley D’Sa Ulla Randen Agnieszka Małecka Josephine M. I. Vos Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for Therapy Hemato cold agglutinin disease autoimmune hemolytic anemia lymphoproliferative monoclonal gammopathy Waldenström’s macroglobulinemia complement |
| title | Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for Therapy |
| title_full | Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for Therapy |
| title_fullStr | Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for Therapy |
| title_full_unstemmed | Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for Therapy |
| title_short | Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for Therapy |
| title_sort | cold agglutinin disease improved understanding of pathogenesis helps define targets for therapy |
| topic | cold agglutinin disease autoimmune hemolytic anemia lymphoproliferative monoclonal gammopathy Waldenström’s macroglobulinemia complement |
| url | https://www.mdpi.com/2673-6357/3/4/40 |
| work_keys_str_mv | AT sigbjørnberentsen coldagglutinindiseaseimprovedunderstandingofpathogenesishelpsdefinetargetsfortherapy AT shirleydsa coldagglutinindiseaseimprovedunderstandingofpathogenesishelpsdefinetargetsfortherapy AT ullaranden coldagglutinindiseaseimprovedunderstandingofpathogenesishelpsdefinetargetsfortherapy AT agnieszkamałecka coldagglutinindiseaseimprovedunderstandingofpathogenesishelpsdefinetargetsfortherapy AT josephinemivos coldagglutinindiseaseimprovedunderstandingofpathogenesishelpsdefinetargetsfortherapy |