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Abnormal natural killer cell physiology

MedGen UID:
868613
Concept ID:
C4023012
Pathologic Function
HPO: HP:0012177

Definition

A functional anomaly of the natural killer cell. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAbnormal natural killer cell physiology

Conditions with this feature

Familial hemophagocytic lymphohistiocytosis 5
MedGen UID:
416514
Concept ID:
C2751293
Disease or Syndrome
Familial hemophagocytic lymphohistiocytosis-5 with or without microvillus inclusion disease (FHL5) is an autosomal recessive hyperinflammatory disorder characterized clinically by fever, hepatosplenomegaly, pancytopenia, coagulation abnormalities, and other laboratory findings. Some patients have neurologic symptoms due to inflammatory CNS disease. There is uncontrolled and ineffective proliferation and activation of T lymphocytes, NK cells, and macrophages that infiltrate multiple organs, including liver, spleen, lymph nodes, and the CNS. The phenotype is variable: some patients may present in early infancy with severe diarrhea, prior to the onset of typical FHL features, whereas others present later in childhood and have a more protracted course without diarrhea. The early-onset diarrhea is due to enteropathy reminiscent of microvillus inclusion disease (see MVID, 251850). The enteropathy, which often necessitates parenteral feeding, may be the most life-threatening issue even after hematopoietic stem cell transplantation (HSCT). More variable features include sensorineural hearing loss and hypogammaglobulinemia. Treatment with immunosuppressive drugs and chemotherapy can ameliorate signs and symptoms of FHL in some patients, but the only curative therapy for FHL is HSCT. HSCT is not curative for enteropathy associated with the disorder, despite hematologic and immunologic reconstitution (summary by Meeths et al., 2010; Pagel et al., 2012; Stepensky et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL, HLH), see 267700.

Professional guidelines

PubMed

Albinger N, Pfeifer R, Nitsche M, Mertlitz S, Campe J, Stein K, Kreyenberg H, Schubert R, Quadflieg M, Schneider D, Kühn MWM, Penack O, Zhang C, Möker N, Ullrich E
Blood Cancer J 2022 Apr 13;12(4):61. doi: 10.1038/s41408-022-00660-2. PMID: 35418180Free PMC Article
Collins C, Sharpe E, Silber A, Kulke S, Hsieh EWY
J Clin Immunol 2021 Jul;41(5):881-895. Epub 2021 May 13 doi: 10.1007/s10875-021-01059-7. PMID: 33987750Free PMC Article
Thenappan T, Ormiston ML, Ryan JJ, Archer SL
BMJ 2018 Mar 14;360:j5492. doi: 10.1136/bmj.j5492. PMID: 29540357Free PMC Article

Recent clinical studies

Etiology

Hou R, Huang R, Zhou Y, Lin D, Xu J, Yang L, Wei X, Xie Z, Zhou Q
Fertil Steril 2023 Mar;119(3):492-503. Epub 2022 Dec 15 doi: 10.1016/j.fertnstert.2022.12.016. PMID: 36528108
Rossetti CL, Cazarin J, Hecht F, Beltrão FEL, Ferreira ACF, Fortunato RS, Ramos HE, de Carvalho DP
Front Endocrinol (Lausanne) 2022;13:1041676. Epub 2022 Dec 19 doi: 10.3389/fendo.2022.1041676. PMID: 36601011Free PMC Article
Wu X, Liu Y, Jin S, Wang M, Jiao Y, Yang B, Lu X, Ji X, Fei Y, Yang H, Zhao L, Chen H, Zhang Y, Li H, Lipsky PE, Tsokos GC, Bai F, Zhang X
Nat Commun 2021 Aug 17;12(1):4977. doi: 10.1038/s41467-021-25246-7. PMID: 34404786Free PMC Article
Wang J, Xu Y, Chen Z, Liang J, Lin Z, Liang H, Xu Y, Wu Q, Guo X, Nie J, Lu B, Huang B, Xian H, Wang X, Wu Q, Zeng J, Chai C, Zhang M, Lin Y, Zhang L, Zhao S, Tong Y, Zeng L, Gu X, Chen ZG, Yi S, Zhang T, Delfouneso D, Zhang Y, Nutt SL, Lew AM, Lu L, Bai F, Xia H, Wen Z, Zhang Y
Cell 2020 Dec 23;183(7):1867-1883.e26. Epub 2020 Nov 27 doi: 10.1016/j.cell.2020.10.048. PMID: 33248023
Thenappan T, Ormiston ML, Ryan JJ, Archer SL
BMJ 2018 Mar 14;360:j5492. doi: 10.1136/bmj.j5492. PMID: 29540357Free PMC Article

Diagnosis

Regan L, Rai R, Saravelos S, Li TC; Royal College of Obstetricians and Gynaecologists
BJOG 2023 Nov;130(12):e9-e39. Epub 2023 Jun 19 doi: 10.1111/1471-0528.17515. PMID: 37334488
Rossetti CL, Cazarin J, Hecht F, Beltrão FEL, Ferreira ACF, Fortunato RS, Ramos HE, de Carvalho DP
Front Endocrinol (Lausanne) 2022;13:1041676. Epub 2022 Dec 19 doi: 10.3389/fendo.2022.1041676. PMID: 36601011Free PMC Article
Bozkurt B, Kamat I, Hotez PJ
Circulation 2021 Aug 10;144(6):471-484. Epub 2021 Jul 20 doi: 10.1161/CIRCULATIONAHA.121.056135. PMID: 34281357Free PMC Article
Thenappan T, Ormiston ML, Ryan JJ, Archer SL
BMJ 2018 Mar 14;360:j5492. doi: 10.1136/bmj.j5492. PMID: 29540357Free PMC Article
Gerfaud-Valentin M, Jamilloux Y, Iwaz J, Sève P
Autoimmun Rev 2014 Jul;13(7):708-22. Epub 2014 Mar 19 doi: 10.1016/j.autrev.2014.01.058. PMID: 24657513

Therapy

Regan L, Rai R, Saravelos S, Li TC; Royal College of Obstetricians and Gynaecologists
BJOG 2023 Nov;130(12):e9-e39. Epub 2023 Jun 19 doi: 10.1111/1471-0528.17515. PMID: 37334488
Pan S, Guan J, Xianyu B, Tan Y, Li T, Xu H
Adv Mater 2023 Jun;35(23):e2211370. Epub 2023 Apr 27 doi: 10.1002/adma.202211370. PMID: 36917826
Bozkurt B, Kamat I, Hotez PJ
Circulation 2021 Aug 10;144(6):471-484. Epub 2021 Jul 20 doi: 10.1161/CIRCULATIONAHA.121.056135. PMID: 34281357Free PMC Article
Liu S, Galat V, Galat Y, Lee YKA, Wainwright D, Wu J
J Hematol Oncol 2021 Jan 6;14(1):7. doi: 10.1186/s13045-020-01014-w. PMID: 33407739Free PMC Article
Wang J, Xu Y, Chen Z, Liang J, Lin Z, Liang H, Xu Y, Wu Q, Guo X, Nie J, Lu B, Huang B, Xian H, Wang X, Wu Q, Zeng J, Chai C, Zhang M, Lin Y, Zhang L, Zhao S, Tong Y, Zeng L, Gu X, Chen ZG, Yi S, Zhang T, Delfouneso D, Zhang Y, Nutt SL, Lew AM, Lu L, Bai F, Xia H, Wen Z, Zhang Y
Cell 2020 Dec 23;183(7):1867-1883.e26. Epub 2020 Nov 27 doi: 10.1016/j.cell.2020.10.048. PMID: 33248023

Prognosis

Liu DL, Wang YJ, Qian SY, Ma SS, Ding MJ, Dong M, Zhang JM, Zhang MZ, Chen QJ, Zhang XD
Hematology 2024 Dec;29(1):2307817. Epub 2024 Feb 6 doi: 10.1080/16078454.2024.2307817. PMID: 38319083
Rossetti CL, Cazarin J, Hecht F, Beltrão FEL, Ferreira ACF, Fortunato RS, Ramos HE, de Carvalho DP
Front Endocrinol (Lausanne) 2022;13:1041676. Epub 2022 Dec 19 doi: 10.3389/fendo.2022.1041676. PMID: 36601011Free PMC Article
Sun C, Sun HY, Xiao WH, Zhang C, Tian ZG
Acta Pharmacol Sin 2015 Oct;36(10):1191-9. Epub 2015 Jun 15 doi: 10.1038/aps.2015.41. PMID: 26073325Free PMC Article
Gerfaud-Valentin M, Jamilloux Y, Iwaz J, Sève P
Autoimmun Rev 2014 Jul;13(7):708-22. Epub 2014 Mar 19 doi: 10.1016/j.autrev.2014.01.058. PMID: 24657513
Giannouli S, Kanellopoulou T, Voulgarelis M
Curr Opin Rheumatol 2012 Jan;24(1):97-102. doi: 10.1097/BOR.0b013e32834db4ee. PMID: 22157417

Clinical prediction guides

Hou R, Huang R, Zhou Y, Lin D, Xu J, Yang L, Wei X, Xie Z, Zhou Q
Fertil Steril 2023 Mar;119(3):492-503. Epub 2022 Dec 15 doi: 10.1016/j.fertnstert.2022.12.016. PMID: 36528108
Rossetti CL, Cazarin J, Hecht F, Beltrão FEL, Ferreira ACF, Fortunato RS, Ramos HE, de Carvalho DP
Front Endocrinol (Lausanne) 2022;13:1041676. Epub 2022 Dec 19 doi: 10.3389/fendo.2022.1041676. PMID: 36601011Free PMC Article
Albinger N, Pfeifer R, Nitsche M, Mertlitz S, Campe J, Stein K, Kreyenberg H, Schubert R, Quadflieg M, Schneider D, Kühn MWM, Penack O, Zhang C, Möker N, Ullrich E
Blood Cancer J 2022 Apr 13;12(4):61. doi: 10.1038/s41408-022-00660-2. PMID: 35418180Free PMC Article
Wang J, Xu Y, Chen Z, Liang J, Lin Z, Liang H, Xu Y, Wu Q, Guo X, Nie J, Lu B, Huang B, Xian H, Wang X, Wu Q, Zeng J, Chai C, Zhang M, Lin Y, Zhang L, Zhao S, Tong Y, Zeng L, Gu X, Chen ZG, Yi S, Zhang T, Delfouneso D, Zhang Y, Nutt SL, Lew AM, Lu L, Bai F, Xia H, Wen Z, Zhang Y
Cell 2020 Dec 23;183(7):1867-1883.e26. Epub 2020 Nov 27 doi: 10.1016/j.cell.2020.10.048. PMID: 33248023
Xiong J, Zhao WL
J Hematol Oncol 2018 Dec 4;11(1):134. doi: 10.1186/s13045-018-0678-1. PMID: 30514323Free PMC Article

Recent systematic reviews

Woon EV, Day A, Bracewell-Milnes T, Male V, Johnson M
J Reprod Immunol 2020 Nov;142:103189. Epub 2020 Aug 22 doi: 10.1016/j.jri.2020.103189. PMID: 32889304
Yang X, Yang Y, Yuan Y, Liu L, Meng T
Biomed Res Int 2020;2020:4808072. Epub 2020 Mar 28 doi: 10.1155/2020/4808072. PMID: 32309433Free PMC Article
Eaton-Fitch N, du Preez S, Cabanas H, Staines D, Marshall-Gradisnik S
Syst Rev 2019 Nov 14;8(1):279. doi: 10.1186/s13643-019-1202-6. PMID: 31727160Free PMC Article
Tang AW, Alfirevic Z, Quenby S
Hum Reprod 2011 Aug;26(8):1971-80. Epub 2011 May 25 doi: 10.1093/humrep/der164. PMID: 21613313
Lyall M, Peakman M, Wessely S
J Psychosom Res 2003 Aug;55(2):79-90. doi: 10.1016/s0022-3999(02)00515-9. PMID: 12932505

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