Details of Disease

General Information of Disease (ID: DISCMFL6)

• Disease Name: Immunodeficiency 32B
• Synonyms: Epstein-Barr VIRUS, susceptibility to chronic infection by; CAEBV infection; chronic active Epstein-Barr virus infection; chronic active Epstein-Barr disease; CEBV; monocyte and dendritic cell deficiency, autosomal recessive; IRF8 deficiency, autosomal recessive; IMD32B; immunodeficiency 32B; immunodeficiency 32B, monocyte and dendritic cell deficiency, autosomal recessive; chronic Epstein-Barr virus infection syndrome; CAEBV syndrome; immunodeficiency 32B, monocyte, Dendritic cell, and natural Killer cell deficiency, autosomal recessive; chronic EBV infection syndrome
• Definition: A rare progressive disease that begins as a primary Epstein-Barr virus (EBV) infection. In this type of infection, the body makes too many lymphocytes (lymphoproliferative disease) for a period of more than 6 months duration. Lymphocytes are a type of white blood cell. They are an importantpart ofthe immune system because they help fight off diseases and protect the body from infection byproducing antibodies against viruses or bacteria and regulating immune responses. In CAEBV there are many antibodies againstEBV in the blood.Most people (about 95% of adults) get infected with EBV at some point in their lives, and never have any health problems.However, EBV can cause infectiousmononucleosis and other illnesses, and has a role in various autoimmune diseases and some types of cancer. While most infections occurring during childhood do not cause any symptoms,EBV infection in adolescents or young adults can often result in mononucleosis.After an EBV infection, the virus becomes latent (inactive) in the body, and, in some cases, the virus may reactivate. This does not always cause symptoms, but people with weakened immune systems are more likely to develop symptoms if EBV reactivates.In rare cases, people infected with EBV develop chronic active EBV virus infection(CAEBV) without apparent immunodeficiency. Most cases of CAEBV have been reported from Japan. These patientshave some of the complications found in otherwise-healthy patients with acute EBV infection, but unlike healthy patients, these complications persist and progress. Symptoms of CAEBV most often include fever, liverdysfunction, an enlarged spleen (splenomegaly), swollen lymph nodes (lymphadenopathy), and low numbers of platelets (thrombocytopenia) as well as high EBV-DNA load in the blood. Other features that appear in more than 10% of patients include enlarged liver (hepatomegaly), anemia, hypersensitivity to mosquito bites, rash, oral ulcers, hemophagocytic syndrome, coronary artery aneurysms, liver failure, lymphoma, and interstitial pneumonia. While the cause is yet unknown, researchers have identified defects in T cells or natural killer (NK) cells activity which results in a decreased defense against the EBV in people with CAEBV.It is important to note that the fatigue and malaise from acute infectious mononucleosis (IM)varies from mild symptoms lasting only a few weeks, to more severe symptoms of fatigue that can persist for several months, or even up to a year or more in up to 10% of patients (which may be considered a less severe form of chronicEBV infection). The persistence of fatigue that is seen in some patients after acute IM would lead some people to believe that EBV may also cause cases of chronic fatigue syndrome (CFS). However, no convincing link has been found between EBV and CFS.Hematopoietic stemcell transplantation has shown promise in the treatment of CAEBV.
• Disease Hierarchy:
  DISYKSRF: Genetic disease
  DISU6QAV: Post-viral disorder
  DISFYSIV: Virus infection
  DISCMFL6: Immunodeficiency 32B
• Disease Identifiers:
  MONDO ID: MONDO_0009194
  UMLS CUI: C4016741
  OMIM ID: 226990
  MedGen ID: 865178
  Orphanet ID: 2566

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
IRF8	TTHUBNK	Strong	Autosomal recessive	[1]
IRF8	TTHUBNK	Strong	Biomarker	[2]

This Disease Is Related to 1 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
IRF8	OT8YSNI4	Strong	Autosomal recessive	[1]

References

• [1] IRF8 mutations and human dendritic-cell immunodeficiency. N Engl J Med. 2011 Jul 14;365(2):127-38. doi: 10.1056/NEJMoa1100066. Epub 2011 Apr 27.
• [2] Biallelic mutations in IRF8 impair human NK cell maturation and function.J Clin Invest. 2017 Jan 3;127(1):306-320. doi: 10.1172/JCI86276. Epub 2016 Nov 28.