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Autoinflammatory syndrome with immunodeficiency(AISIMD)

MedGen UID:
1784363
Concept ID:
C5543547
Disease or Syndrome
Synonym: AUTOINFLAMMATORY SYNDROME, FAMILIAL, WITH OR WITHOUT IMMUNODEFICIENCY
 
Gene (location): SOCS1 (16p13.13)
 
Monarch Initiative: MONDO:0800130
OMIM®: 619375

Definition

Familial autoinflammatory syndrome with or without immunodeficiency (AISIMD) is characterized by onset of various autoimmune features usually in the first decades of life, although later onset has been reported. Typical features include autoimmune cytopenia, hemolytic anemia, thrombocytopenia, and lymphadenopathy. More variable features may include autoimmune thyroiditis, psoriasis or eczema, nephritis, hepatitis, and symptoms of systemic lupus erythematosus (SLE; see 152700). Some patients may have recurrent infections or exacerbation of the disease with acute infection. Laboratory studies show variable findings, often decreased numbers of naive B cells, lymphopenia with skewed subsets, hypogammaglobulinemia, presence of autoantibodies, and a hyperinflammatory state. The disorder shows autosomal dominant inheritance with incomplete penetrance (summary by Hadjadj et al., 2020). [from OMIM]

Clinical features

From HPO
Classic Hodgkin lymphoma
MedGen UID:
9283
Concept ID:
C0019829
Neoplastic Process
Classic Hodgkin lymphoma is a lymph node cancer of germinal center B-cell origin. Hodgkin lymphoma tumors consist of a minority of malignant cells, known as 'Reed-Sternberg' (RS) cells, mixed with reactive lymphocytes and other benign inflammatory cells. A defining feature of RS cells is the presence of 2 nuclei (summary by Salipante et al., 2009).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Coombs-positive hemolytic anemia
MedGen UID:
105458
Concept ID:
C0520736
Disease or Syndrome
A type of hemolytic anemia in which the Coombs test is positive.
Spondylitis
MedGen UID:
11560
Concept ID:
C0038012
Disease or Syndrome
Inflammation of the vertebrae (vertebral bodies) or spine.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Celiac disease
MedGen UID:
3291
Concept ID:
C0007570
Disease or Syndrome
Celiac disease is a systemic autoimmune disease that can be associated with gastrointestinal findings (diarrhea, malabsorption, abdominal pain and distension, bloating, vomiting, and weight loss) and/or highly variable non-gastrointestinal findings (dermatitis herpetiformis, chronic fatigue, joint pain/inflammation, iron deficiency anemia, migraines, depression, attention-deficit disorder, epilepsy, osteoporosis/osteopenia, infertility and/or recurrent fetal loss, vitamin deficiencies, short stature, failure to thrive, delayed puberty, dental enamel defects, and autoimmune disorders). Classic celiac disease, characterized by mild to severe gastrointestinal symptoms, is less common than non-classic celiac disease, characterized by absence of gastrointestinal symptoms.
Glomerulonephritis
MedGen UID:
6616
Concept ID:
C0017658
Disease or Syndrome
Inflammation of the renal glomeruli.
Systemic lupus erythematosus
MedGen UID:
6146
Concept ID:
C0024141
Disease or Syndrome
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by production of autoantibodies against nuclear, cytoplasmic, and cell surface molecules that transcend organ-specific boundaries. Tissue deposition of antibodies or immune complexes induces inflammation and subsequent injury of multiple organs and finally results in clinical manifestations of SLE, including glomerulonephritis, dermatitis, thrombosis, vasculitis, seizures, and arthritis. Evidence strongly suggests the involvement of genetic components in SLE susceptibility (summary by Oishi et al., 2008). Genetic Heterogeneity of Systemic Lupus Erythematosus An autosomal recessive form of systemic lupus erythematosus (SLEB16; 614420) is caused by mutation in the DNASE1L3 gene (602244) on chromosome 3p14.3. An X-linked dominant form of SLE (SLEB17; 301080) is caused by heterozygous mutation in the TLR7 gene (300365) on chromosome Xp22. See MAPPING and MOLECULAR GENETICS sections for a discussion of genetic heterogeneity of susceptibility to SLE.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Thyroiditis
MedGen UID:
21548
Concept ID:
C0040147
Disease or Syndrome
Inflammation of the thyroid gland.
Antinuclear antibody positivity
MedGen UID:
101792
Concept ID:
C0151480
Laboratory or Test Result
The presence of autoantibodies in the serum that react against nuclei or nuclear components.
Autoimmune thrombocytopenia
MedGen UID:
116621
Concept ID:
C0242584
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Decreased proportion of marginal zone B cells
MedGen UID:
892659
Concept ID:
C4072922
Finding
A reduction in the normal proportion of marginal zone B cells (CD19+/CD27+/IgM+/IgD+) in circulation relative to the total number of B cells.
Decreased proportion of class-switched memory B cells
MedGen UID:
892709
Concept ID:
C4072925
Finding
A reduction in the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM+/IgD+) relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA.
Anti-U1 ribonucleoprotein antibody positivity
MedGen UID:
1770556
Concept ID:
C5421559
Laboratory or Test Result
The presence autoantibodies in the serum that react to proteins (70 Kd, A, C) that are associated with U1 RNA and form U1snRNP.
Anti-dsDNA antibody positivity
MedGen UID:
1782602
Concept ID:
C5539409
Laboratory or Test Result
The presence of autoantibodies (immunoglobulins) in the serum that react against double-stranded DNA.

Professional guidelines

PubMed

Grim A, Veiga KR, Saad N
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Recent clinical studies

Etiology

Zhang J, Lee PY, Aksentijevich I, Zhou Q
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Diagnosis

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Spoor J, Farajifard H, Rezaei N
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Papa R, Lachmann HJ
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Therapy

Grim A, Veiga KR, Saad N
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Prognosis

de Valence B, Delaune M, Nguyen Y, Jachiet V, Heiblig M, Jean A, Riescher Tuczkiewicz S, Henneton P, Guilpain P, Schleinitz N, Le Guenno G, Lobbes H, Lacombe V, Ardois S, Lazaro E, Langlois V, Outh R, Vinit J, Martellosio JP, Decker P, Moulinet T, Dieudonné Y, Bigot A, Terriou L, Vlakos A, de Maleprade B, Denis G, Broner J, Kostine M, Humbert S, Lifermann F, Samson M, Pechuzal S, Aouba A, Kosmider O, Dion J, Grosleron S, Bourguiba R, Terrier B, Georgin-Lavialle S, Fain O, Mekinian A, Morgand M, Comont T, Hadjadj J; French VEXAS Group
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Clinical prediction guides

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Recent systematic reviews

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