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Reduced natural killer cell activity

MedGen UID:
333452
Concept ID:
C1839969
Finding
HPO: HP:0012178

Definition

Reduced ability of the natural killer cell to function in the adaptive immune response. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVReduced natural killer cell activity

Conditions with this feature

Wiskott-Aldrich syndrome
MedGen UID:
21921
Concept ID:
C0043194
Disease or Syndrome
The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes caused by pathogenic variants in WAS. WAS-related disorders usually present in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; eczema; and recurrent bacterial and viral infections, particularly of the ear. At least 40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, rheumatoid arthritis, vasculitis, and immune-mediated damage to the kidneys and liver. Individuals with a WAS-related disorder, particularly those who have been exposed to Epstein-Barr virus (EBV), are at increased risk of developing lymphomas, which often occur in unusual, extranodal locations including the brain, lung, or gastrointestinal tract. Males with XLT have thrombocytopenia with small platelets; other complications of Wiskott-Aldrich syndrome, including eczema and immune dysfunction, are usually mild or absent. Males with XLN have congenital neutropenia, myeloid dysplasia, and lymphoid cell abnormalities.
X-linked severe combined immunodeficiency
MedGen UID:
220906
Concept ID:
C1279481
Disease or Syndrome
The phenotypic spectrum of X-linked severe combined immunodeficiency (X-SCID) ranges from typical X-SCID (early-onset disease in males that is fatal if not treated with hematopoietic stem cell transplantation [HSCT] or gene therapy) to atypical X-SCID (later-onset disease comprising phenotypes caused by variable immunodeficiency, immune dysregulation, and/or autoimmunity). Typical X-SCID. Prior to universal newborn screening (NBS) for SCID most males with typical X-SCID came to medical attention between ages three and six months because of recurrent infections, persistent infections, and infections with opportunistic organisms. With universal NBS for SCID, the common presentation for typical X-SCID is now an asymptomatic, healthy-appearing male infant. Atypical X-SCID, which usually is not detected by NBS, can manifest in the first years of life or later with one of the following: recurrent upper and lower respiratory tract infections with bronchiectasis; Omenn syndrome, a clinical phenotype caused by immune dysregulation; X-SCID combined immunodeficiency (often with recurrent infections, warts, and dermatitis); immune dysregulation and autoimmunity; or Epstein-Barr virus-related lymphoproliferative complications.
Familial hemophagocytic lymphohistiocytosis 3
MedGen UID:
332383
Concept ID:
C1837174
Disease or Syndrome
Secretion of the contents of cytolytic granules at the immunologic synapse is a highly regulated process essential for lymphocyte cytotoxicity. This process requires the rapid transfer of perforin (170280)-containing lytic granules to the target cell interface, followed by their docking and fusion with the plasma membrane. Familial hemophagocytic lymphohistiocytosis is a genetically heterogeneous condition characterized by defective cytotoxicity. For a more detailed description of FHL, see 267700.
Hermansky-Pudlak syndrome 2
MedGen UID:
374912
Concept ID:
C1842362
Disease or Syndrome
Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. Ocular findings include reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in variable bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects occur primarily in individuals with pathogenic variants in AP3B1 and AP3D1.
Ectodermal dysplasia and immunodeficiency 1
MedGen UID:
375787
Concept ID:
C1846008
Disease or Syndrome
Ectodermal dysplasia with immunodeficiency-1 (EDAID1) is an X-linked recessive disorder that characteristically affects only males. Affected individuals have onset of recurrent severe infections due to immunodeficiency in early infancy or in the first years of life. There is increased susceptibility to bacterial, pneumococcal, mycobacterial, and fungal infections. Laboratory studies usually show dysgammaglobulinemia with low IgG subsets and normal or increased IgA and IgM, consistent with impaired 'class-switching' of B cells, although immunologic abnormalities may be subtle compared to the clinical picture, and B- and T-cell numbers are usually normal. There is a poor antibody response to polysaccharide vaccinations, particularly pneumococcus; response to other vaccinations is variable. Patients also have features of ectodermal dysplasia, including conical incisors, hypo/anhidrosis, and thin skin or hair. Severely affected individuals may also show lymphedema, osteopetrosis, and, rarely, hematologic abnormalities. The phenotype is highly variable, likely due to different hypomorphic mutations, and may be fatal in childhood. Intravenous immunoglobulins and prophylactic antibiotics are used as treatment; some patients may benefit from bone marrow transplantation. Although only males tend to be affected with immunodeficiency, many patients inherit a mutation from a mother who has mild features of IP or conical teeth (summary by Doffinger et al., 2001, Orange et al., 2004, Roberts et al., 2010, Heller et al., 2020). Genetic Heterogeneity of Ectodermal Dysplasia and Immune Deficiency Also see EDAID2 (612132), caused by mutation in the NFKBIA gene (164008).
Familial hemophagocytic lymphohistiocytosis 2
MedGen UID:
400366
Concept ID:
C1863727
Disease or Syndrome
Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia. There is increased production of cytokines, such as gamma-interferon (IFNG; 147570) and TNF-alpha (191160), by hyperactivation and proliferation of T cells and macrophages. Activity of cytotoxic T cells and NK cells is reduced, consistent with a defect in cellular cytotoxicity. Bone marrow, lymph nodes, spleen, and liver show features of hemophagocytosis. Chemotherapy and/or immunosuppressant therapy may result in symptomatic remission, but the disorder is fatal without bone marrow transplantation (summary by Dufourcq-Lagelouse et al., 1999, Stepp et al., 1999, and Molleran Lee et al., 2004). For a general phenotypic description and a discussion of genetic heterogeneity of FHL, see 267700.
Wiskott-Aldrich syndrome 2
MedGen UID:
482631
Concept ID:
C3281001
Disease or Syndrome
Wiskott-Aldrich syndrome-2 (WAS2) is an autosomal recessive immunologic disorder characterized by onset of recurrent infections in infancy. Other features include thrombocytopenia with normal platelet volume and eczema. Laboratory studies show decreased CD8+ T cells, variably increased Ig, particularly IgE, low B cells, aberrant function of T and NK cells, and impaired T-cell migration. The cellular abnormalities are thought to result from defective F-actin polymerization. Death in early childhood may occur; hematopoietic stem cell transplantation is curative (summary by Lanzi et al., 2012). For a discussion of genetic heterogeneity of Wiskott-Aldrich syndrome, see WAS (301000).
Autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD
MedGen UID:
816258
Concept ID:
C3809928
Disease or Syndrome
Autoimmune lymphoproliferative syndrome type III is an autosomal recessive disorder of immune dysregulation. The phenotype is variable, but most patients have significant lymphadenopathy associated with variable autoimmune manifestations. Some patients may have recurrent infections. Lymphocyte accumulation results from a combination of impaired apoptosis and excessive proliferation (summary by Oliveira, 2013). For a general description and a discussion of genetic heterogeneity of ALPS, see 601859.
Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity
MedGen UID:
816672
Concept ID:
C3810342
Disease or Syndrome
Immunodeficiency-20 is a rare autosomal recessive primary immunodeficiency characterized by functional deficiency of NK cells. Patient NK cells are defective in spontaneous cell cytotoxicity, but retain antibody-dependent cellular cytotoxicity. Patients typically present early in childhood with severe herpes viral infections, particularly Epstein Barr virus (EBV), and human papillomavirus (HPV) (summary by Grier et al., 2012).
Periodic fever-infantile enterocolitis-autoinflammatory syndrome
MedGen UID:
863504
Concept ID:
C4015067
Disease or Syndrome
Autoinflammation with infantile enterocolitis is an autosomal dominant disorder characterized by onset of recurrent flares of autoinflammation in early infancy. Affected individuals tend to have poor overall growth and gastrointestinal symptoms in infancy associated with laboratory evidence of activated inflammation. This initial presentation is followed by recurrent febrile episodes with splenomegaly and sometimes hematologic disturbances, arthralgias, or myalgias. The disorder results from overactivation of an arm of the immune response system (Romberg et al., 2014; Canna et al., 2014).
X-linked lymphoproliferative disease due to SH2D1A deficiency
MedGen UID:
1770239
Concept ID:
C5399825
Disease or Syndrome
X-linked lymphoproliferative disease (XLP) has two recognizable subtypes, XLP1 and XLP2. XLP1 is characterized predominantly by one of three commonly recognized phenotypes: Inappropriate immune response to Epstein-Barr virus (EBV) infection leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis. Dysgammaglobulinemia. Lymphoproliferative disease (malignant lymphoma). XLP2 is most often characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease. HLH resulting from EBV infection is associated with an unregulated and exaggerated immune response with widespread proliferation of cytotoxic T cells, EBV-infected B cells, and macrophages. Dysgammaglobulinemia is typically hypogammaglobulinemia of one or more immunoglobulin subclasses. The malignant lymphomas are typically B-cell lymphomas, non-Hodgkin type, often extranodal, and in particular involving the intestine.
Immunodeficiency 14b, autosomal recessive
MedGen UID:
1787468
Concept ID:
C5543301
Disease or Syndrome
Autosomal recessive primary immunodeficiency-14B (IMD14B) is characterized by onset of recurrent infections in early childhood. Most patients have respiratory infections, but some may develop inflammatory bowel disease or osteomyelitis. Laboratory studies tend to show hypogammaglobulinemia and decreased levels of B cells. Although NK cell and T cell numbers are normal, there may be evidence of impaired immune-mediated cytotoxicity and defective T-cell function (summary by et al., 2018 and et al., 2019).
Immunodeficiency 81
MedGen UID:
1788669
Concept ID:
C5543540
Disease or Syndrome
Immunodeficiency-81 (IMD81) is an autosomal recessive complex disorder with onset of recurrent infections, including fungal infections, in early infancy, associated with T-cell, neutrophil, and NK dysfunction. B cells may also show maturation abnormalities. Other features include autoimmune hemolytic anemia and abnormal platelet aggregation, indicating a complex disorder with a wide range of hematopoietic disturbances. The disorder is caused by a defect in intracellular signaling pathways (summary by Lev et al., 2021).

Professional guidelines

PubMed

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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
Wrona E, Borowiec M, Potemski P
Int J Mol Sci 2021 May 31;22(11) doi: 10.3390/ijms22115899. PMID: 34072732Free PMC Article

Recent clinical studies

Etiology

Spiegel D
Br J Health Psychol 2014 Sep;19(3):465-85. Epub 2013 Aug 26 doi: 10.1111/bjhp.12061. PMID: 23980690
Maity R, Nair SR, Caspi RR, Nelson LM
Am J Reprod Immunol 1997 Nov;38(5):360-5. doi: 10.1111/j.1600-0897.1997.tb00312.x. PMID: 9352028
Ratcliffe LT, Mackenzie CR, Lukey PT, Ress SR
Scand J Immunol Suppl 1992;11:167-70. doi: 10.1111/j.1365-3083.1992.tb01643.x. PMID: 1514034
Araga S, Kagimoto H, Funamoto K, Takahashi K
Acta Neurol Scand 1991 Sep;84(3):259-63. doi: 10.1111/j.1600-0404.1991.tb04948.x. PMID: 1950471
Miller EB, Hiserodt JC, Hunt LE, Steen VD, Medsger TA Jr
Arthritis Rheum 1988 Dec;31(12):1515-23. doi: 10.1002/art.1780311208. PMID: 3196366

Diagnosis

Kim CK, Choi YM, Bae E, Jue MS, So HS, Hwang ES
PLoS One 2018;13(2):e0193299. Epub 2018 Feb 21 doi: 10.1371/journal.pone.0193299. PMID: 29466462Free PMC Article
Mathews HL, Konley T, Kosik KL, Krukowski K, Eddy J, Albuquerque K, Janusek LW
Brain Behav Immun 2011 Jul;25(5):830-9. Epub 2010 Dec 10 doi: 10.1016/j.bbi.2010.12.002. PMID: 21146603Free PMC Article
Witek-Janusek L, Gabram S, Mathews HL
Psychoneuroendocrinology 2007 Jan;32(1):22-35. Epub 2006 Nov 7 doi: 10.1016/j.psyneuen.2006.09.011. PMID: 17092654Free PMC Article
Nelson LM
J Soc Gynecol Investig 2001 Jan-Feb;8(1 Suppl Proceedings):S55-7. doi: 10.1016/s1071-5576(00)00110-6. PMID: 11223375
Pisani RJ
Mayo Clin Proc 1993 Apr;68(4):386-92. doi: 10.1016/s0025-6196(12)60137-2. PMID: 8455400

Therapy

Kim CK, Choi YM, Bae E, Jue MS, So HS, Hwang ES
PLoS One 2018;13(2):e0193299. Epub 2018 Feb 21 doi: 10.1371/journal.pone.0193299. PMID: 29466462Free PMC Article
Seifert S, Bub A, Franz CM, Watzl B
J Nutr 2011 May;141(5):978-84. Epub 2011 Mar 23 doi: 10.3945/jn.110.136440. PMID: 21430250
Witek-Janusek L, Gabram S, Mathews HL
Psychoneuroendocrinology 2007 Jan;32(1):22-35. Epub 2006 Nov 7 doi: 10.1016/j.psyneuen.2006.09.011. PMID: 17092654Free PMC Article
Frank MG, Hendricks SE, Johnson DR, Wieseler JL, Burke WJ
Neuropsychobiology 1999;39(1):18-24. doi: 10.1159/000026555. PMID: 9892855
Maity R, Nair SR, Caspi RR, Nelson LM
Am J Reprod Immunol 1997 Nov;38(5):360-5. doi: 10.1111/j.1600-0897.1997.tb00312.x. PMID: 9352028

Prognosis

Fabrazzo M, Cipolla S, Signoriello S, Camerlengo A, Calabrese G, Giordano GM, Argenziano G, Galderisi S
Eur Psychiatry 2021 Nov 25;64(1):e71. doi: 10.1192/j.eurpsy.2021.2249. PMID: 34819201Free PMC Article
Spiegel D
Br J Health Psychol 2014 Sep;19(3):465-85. Epub 2013 Aug 26 doi: 10.1111/bjhp.12061. PMID: 23980690
Sashihara T, Nagata M, Mori T, Ikegami S, Gotoh M, Okubo K, Uchida M, Itoh H
Appl Physiol Nutr Metab 2013 Dec;38(12):1228-35. Epub 2013 Jun 11 doi: 10.1139/apnm-2012-0490. PMID: 24195623
Pisani RJ
Mayo Clin Proc 1993 Apr;68(4):386-92. doi: 10.1016/s0025-6196(12)60137-2. PMID: 8455400
Neri A, Brugiatelli M, Ozger Topuz U, Astaldi G
Boll Ist Sieroter Milan 1981 Nov;60(5):394-407. PMID: 7041921

Clinical prediction guides

Kim CK, Choi YM, Bae E, Jue MS, So HS, Hwang ES
PLoS One 2018;13(2):e0193299. Epub 2018 Feb 21 doi: 10.1371/journal.pone.0193299. PMID: 29466462Free PMC Article
Spiegel D
Br J Health Psychol 2014 Sep;19(3):465-85. Epub 2013 Aug 26 doi: 10.1111/bjhp.12061. PMID: 23980690
Witek-Janusek L, Gabram S, Mathews HL
Psychoneuroendocrinology 2007 Jan;32(1):22-35. Epub 2006 Nov 7 doi: 10.1016/j.psyneuen.2006.09.011. PMID: 17092654Free PMC Article
Villa ML, Ferrario E, Bergamasco E, Bozzetti F, Cozzaglio L, Clerici E
Br J Cancer 1991 Jun;63(6):1010-4. doi: 10.1038/bjc.1991.219. PMID: 2069835Free PMC Article
Miller EB, Hiserodt JC, Hunt LE, Steen VD, Medsger TA Jr
Arthritis Rheum 1988 Dec;31(12):1515-23. doi: 10.1002/art.1780311208. PMID: 3196366

Recent systematic reviews

Fabrazzo M, Cipolla S, Signoriello S, Camerlengo A, Calabrese G, Giordano GM, Argenziano G, Galderisi S
Eur Psychiatry 2021 Nov 25;64(1):e71. doi: 10.1192/j.eurpsy.2021.2249. PMID: 34819201Free PMC Article
Spiegel D
Br J Health Psychol 2014 Sep;19(3):465-85. Epub 2013 Aug 26 doi: 10.1111/bjhp.12061. PMID: 23980690

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