Original Research ARTICLE
Natural Killer cell degranulation defect: a cause for impaired NK-cell cytotoxicity and hyperinflammation in Fanconi Anemia patients
- 1National Institute of Immunohaematology (ICMR), India
- 2Division of Immunology, Bai Jerbai Wadia Hospital for Children, India
- 3Bai Jerbai Wadia Hospital for Children, India
- 4Surya Hospitals, India
- 5King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, India
- 6National Institute of Virology (ICMR), India
Fanconi anemia (FA) is a rare inherited syndrome characterized by progressive bone marrow failure (BMF), abnormal skin pigmentation, short stature and increased cancer risk. BMF in FA is multifactorial and largely results from death of hematopoietic stem cells due to genomic instability. Also, inflammatory pathology in FA has been previously reported, however the mechanism is still not clear. In literature, decreased NK-cell count and/or impaired NK-cell activity along with other immunological abnormalities has been described in FA-patients (Myers et al. 2017). However, to the best of our knowledge, this is the first report showing defective degranulation mechanism leading to abnormal NK-cell cytotoxicity in FA-patients which may explain the development of hyperinflammatory response in these patients. This may predispose some patients to develop Hemophagocytic lymphohistiocytosis (HLH) which manifests with prolonged fever, progressive cytopenias and organomegaly. Early diagnosis and initiation of immunosuppressive therapy in these patients will help in better management of these patients. We also propose FA genes to be listed as a cause of familial HLH.
Keywords: Fanconi Anemia, NK cell degranulation defect, Familial Hemophagocytic Lymphohistiocytosis (FHL), HLH-targeted therapy, hyperinflammation
Received: 10 Sep 2018;
Accepted: 22 Feb 2019.
Edited by:Guzide Aksu, Ege University, Turkey
Reviewed by:Gunnur Deniz, Istanbul University, Turkey
Grover C. Bagby, Oregon Health & Science University, United States
Copyright: © 2019 SHABRISH, Kelkar, Chavan, Taur, Desai, Bargir, Gupta, Mehta, Chichra, S, Saxena, Vundinti and Madkaikar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Madhura Kelkar, National Institute of Immunohaematology (ICMR), Mumbai, India, firstname.lastname@example.org
Dr. Manisha Madkaikar, National Institute of Immunohaematology (ICMR), Mumbai, India, email@example.com