Information on CVID14
Basic details
Name: Immunodeficiency, common variable, 14 | Acronym: CVID14
Alt. names: IRF2BP2 haploinsufficiency
Gene: IRF2BP2 | MOI: Autosomal dominant | Mechanism of action: Haploinsufficiency
No. of cases in DB: 18 | First reported in: 2016
Last updated on: 2024-03-14 16:59:56 by Andrés Caballero-Oteyza
Description
Only a dozen patients have been reported to date with this condition. Keller et al. (2016) identified one family with 3 members affected by common variable immunodeficiency (CVID). Patients presented with a history of recurrent sinopulmonary infections since early childhood, hypogammaglobulinemia with undetectable IgG and IgA, impaired vaccine responses, and decreased levels of switched memory B cells. Two of these patients were also affected by autoimmune conditions such as type 1 diabetes and psoriasis, respectively. More recently, two additional studies reporting LOF mutations have been published (PMID: 34451894, 33864888). Palmroth et al. (2021) reported a patient with a similar but more inflammatory phenotype than those reported by Keller et al in 2016. This subject showed increased protein levels, constitutive phosphorylation of STAT5 in CD4 T cells, and increased constitutive activation of STAT1 with upregulated JAK-STAT signalling and expression of interferon-inducible genes. Baxter et al. (2022) reported a young girl with chronic diarrhea, severe eczema, anemia, failure to thrive, fevers, short stature, recurrent infections, cataracts, hypodontia, hypotrichosis alopecia, and hypogammaglobulinemia. In 2023, another study reported 5 additional cases, 3 of them diagnosed with CVID, who carried presumed LOF frameshift variants (PMID:37876937).
Management
Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial. Refs. PMIDs: 27016798
18 reported cases added to GenIA
| SubjectID | Sex | Fam.ID | AD | AFM | Validity | Country | Population | Reference & Pub.code |
|---|---|---|---|---|---|---|---|---|
102138 |
M | 214393 |
65 | 45 | U.S.A. | North American | PMID:27016798 [Fam.Patient:II.2(F)]; PMID:37876937 [Fam.A:II.1(A.3)] | |
| 102141 |
F | 214393 |
24 | 17 | U.S.A. | North American | PMID:27016798 [Patient(III.1)]; PMID:37876937 [Fam.A:III.1(A.1)] | |
| 102142 |
M | 214393 |
26 | 14 | U.S.A. | North American | PMID:27016798 [Fam.Patient:III.2(B)]; PMID:37876937 [Fam.A:III.2(A.2)] | |
| 104864 |
F | 215598 |
4 | Possible | PMID:33864888 [S125]; PMID:37876937 [Fam.B:II.1(B.1)] | |||
| 104923 |
M | 215620 |
33 | 8 | Germany | PMID:36193988 [Patient(II.1)]; PMID:37876937 [Fam.D:II.1(D.1)] | ||
| 105149 |
M | 215654 |
21 | 14 | China | Chinese (China) | PMID:37350971 [Patient(II.1)]; PMID:37876937 [Fam.E:II.1(E.1)] | |
| 105746 |
M | 215851 |
57 | 51 | Finland | Finnish | PMID:34451894 [Patient(II.2)]; PMID:37876937 [Fam.C:II.2(C.1)] | |
| 105761 |
F | 215851 |
71 | 60 | Finland | Finnish | PMID:34451894 [Fam.Patient:II.1(sister)]; PMID:37876937 [Fam.C:II.1(C.2)] | |
| 105791 |
F | 215877 |
45 | 22 | Definitive | Spain | Spanish | PMID:37876937 [Fam.1:II.1(1.1)] |
| 105793 |
M | 215877 |
70 | Definitive | Spain | Spanish | PMID:37876937 [Fam.1:I.2(1.2)] | |
| 105794 |
M | 215878 |
31 | Definitive | Spain | Spanish | PMID:37876937 [Fam.2:II.1(2.1)] | |
| 105839 |
M | 215888 |
26 | 14 | Possible | Spain | Romani | PMID:37876937 [Fam.3:II.1(3.1)] |
| 105844 |
M | 215889 |
15 | Definitive | Spain | Spanish | PMID:37876937 [Fam.4:II.1(4.1)] | |
| 105847 |
M | 215890 |
13 | 1 | Unclear | Spain | Spanish | PMID:37876937 [Fam.5:II.1(5.1)] |
| 106794 |
F | 216145 |
29 | Definitive | Germany | German | PMID:34619682 [P.263]; PMID:39059757 [Fam.1:II.2(P2)] | |
| 106807 |
F | 216145 |
27 | 14 | Definitive | Germany | German | PMID:34619682 [P.159]; PMID:39059757 [Fam.1:II.1(P1)] |
| 106811 |
M | 216157 | 36 | 25 | Definitive | Germany | German | PMID:39059757 [P3] |
| 106812 |
F | 216158 | 33 | 12 | Definitive | Germany | PMID:39059757 [P4] |
AD: Age at genetic diagnosis; AFM: age at first manifestation; PMID: PubMed ID; GRID: GenIA reference ID (ref. not in PubMed).
Summary of clinical findings
[Considering only Definitive and Possible cases]
| Rank | Clinical term | Present | Absent | Unreported |
|---|---|---|---|---|
| 1 | Hypogammaglobulinemia |
16 (94.1%) | 0 (0.0%) | 1 (5.9%) |
| 2 | (unusual) Respiratory tract infection |
13 (76.5%) | 0 (0.0%) | 4 (23.5%) |
| 3 | Decreased proportion of switched memory B cells |
10 (58.8%) | 0 (0.0%) | 7 (41.2%) |
| 4 | Decreased IgG levels |
10 (58.8%) | 0 (0.0%) | 7 (41.2%) |
| 5 | Decreased IgA levels |
9 (52.9%) | 1 (5.9%) | 7 (41.2%) |
| 6 | Lung disease |
9 (52.9%) | 0 (0.0%) | 8 (47.1%) |
| 7 | Decreased IgM levels |
8 (47.1%) | 2 (11.8%) | 7 (41.2%) |
| 8 | Bronchiectasis |
5 (29.4%) | 0 (0.0%) | 12 (70.6%) |
| 9 | Enteropathy |
5 (29.4%) | 0 (0.0%) | 12 (70.6%) |
| 10 | Pneumonia |
5 (29.4%) | 0 (0.0%) | 12 (70.6%) |
| 11 | Reduced NK cell number |
4 (23.5%) | 1 (5.9%) | 12 (70.6%) |
| 12 | Recurrent upper respiratory tract infection |
4 (23.5%) | 0 (0.0%) | 13 (76.5%) |
| 13 | Common variable immunodeficiency |
4 (23.5%) | 0 (0.0%) | 13 (76.5%) |
| 14 | Autoimmunity |
4 (23.5%) | 2 (11.8%) | 11 (64.7%) |
| 15 | Immunodeficiency |
4 (23.5%) | 0 (0.0%) | 13 (76.5%) |
| 16 | Panhypogammaglobulinemia |
4 (23.5%) | 0 (0.0%) | 13 (76.5%) |
| 17 | Negative ab-response to vaccination |
3 (17.7%) | 0 (0.0%) | 14 (82.4%) |
| 18 | Reduced IgG2 levels |
3 (17.7%) | 0 (0.0%) | 14 (82.4%) |
| 19 | Endocrine system abnormality |
3 (17.7%) | 0 (0.0%) | 14 (82.4%) |
| 20 | Increased proportion of transitional B cells |
3 (17.7%) | 0 (0.0%) | 14 (82.4%) |
| 21 | Diarrhea |
3 (17.7%) | 0 (0.0%) | 14 (82.4%) |
| 22 | Acne inversa |
3 (17.7%) | 0 (0.0%) | 14 (82.4%) |
| 23 | Increased proportion of CD21low B cells |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 24 | Oral ulcer |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 25 | Sinusitis |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 26 | Colitis |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 27 | Recurrent lower respiratory tract infections |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 28 | Lymphopenia |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 29 | Psoriasiform dermatitis |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 30 | Type I diabetes mellitus |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 31 | Decreased proportion of plasmablasts |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 32 | Recurrent fevers |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 33 | Increased proportion of naive B cells |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 34 | Splenomegaly |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 35 | Abnormal lymphoproliferation |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 36 | Recurrent infections |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 37 | Neutropenia |
2 (11.8%) | 1 (5.9%) | 14 (82.4%) |
| 38 | Anemia |
2 (11.8%) | 1 (5.9%) | 14 (82.4%) |
| 39 | Pulmonary Emphysema |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 40 | Crohn's disease |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 41 | Bronchitis |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 42 | Arthritis |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 43 | Reduced proportion of naive CD8 T cells |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 44 | Decreased proportion of marginal zone B cells |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 45 | Increased circulating IL-6 |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 46 | Otitis media |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 47 | Reduced antigen-specific T cell proliferation |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 48 | Cataract |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 49 | Impaired Ig class switch recombination |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 50 | Reduced IgG4 levels |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 51 | Thrombocytopenia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 52 | Recurrent infections of the middle ear |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 53 | Lymphadenopathy |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 54 | Pectus carinatum |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 55 | Autoimmune neutropenia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 56 | Chronic idiopathic urticaria |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 57 | Osteopenia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 58 | Increased serum TNF-alpha |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 59 | Gastrointestinal lymphocytic infiltration |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 60 | Parapharyngeal abscess |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 61 | Spondyloarthritis |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 62 | Fever |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 63 | Joint laxity |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 64 | Umbilical hernia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 65 | Chronic rhinitis |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 66 | Reduced proportion of CD8 T cells |
1 (5.9%) | 4 (23.5%) | 12 (70.6%) |
| 67 | Increased proportion of CD8 T cells |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 68 | Leukocytosis |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 69 | Increased number of B cells |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 70 | Reduced IgG1 levels |
1 (5.9%) | 2 (11.8%) | 14 (82.4%) |
| 71 | Reduced IgG3 levels |
1 (5.9%) | 2 (11.8%) | 14 (82.4%) |
| 72 | Hepatic necrosis |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 73 | short stature |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 74 | Impaired memory B cell generation |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 75 | Granulomatous-lymphocytic interstitial lung disease |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 76 | Genital ulcers |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 77 | Abdominal distention |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 78 | Autoimmune cytopenia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 79 | Hyperthyroidism |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 80 | Encephalopathy |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 81 | Alopecia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 82 | Atopy |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 83 | Allergy |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 84 | Reduced T cell count |
1 (5.9%) | 3 (17.7%) | 13 (76.5%) |
| 85 | Recurrent bronchopulmonary infections |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 86 | Acute hepatic failure |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 87 | Failure to thrive |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 88 | Acne vulgaris |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 89 | Leukopenia |
1 (5.9%) | 3 (17.7%) | 13 (76.5%) |
| 90 | Varicella zoster virus infection |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 91 | Pancytopenia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 92 | (unusual) Viral infection |
1 (5.9%) | 1 (5.9%) | 15 (88.2%) |
| 93 | Inflammation of the large intestine |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 94 | Neutrophilia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 95 | Increased T cell count |
1 (5.9%) | 2 (11.8%) | 14 (82.4%) |
| 96 | Abnormal weight loss |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 97 | Hemolytic anemia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 98 | Autoimmune antibody positivity |
1 (5.9%) | 2 (11.8%) | 14 (82.4%) |
| 99 | Reduced proportion of CD4 T cells |
1 (5.9%) | 4 (23.5%) | 12 (70.6%) |
| 100 | Abdominal pain |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 101 | Hypertension |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 102 | Eczema |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 103 | Muscular hypotonia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 104 | Hypodontia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 105 | Increased NK cell number |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 106 | Sparse hair |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 107 | Infection of the gastrointestinal tract |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 108 | Polyarthritis |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 109 | Type II diabetes mellitus |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 110 | Decreased lymphocyte proliferation in response to mitogens |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 111 | Abnormal CD4:CD8 ratio |
0 (0.0%) | 3 (17.7%) | 14 (82.4%) |
| 112 | Behavioral abnormality |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 113 | Hepatopathy |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 114 | Cognitive impairment |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 115 | Rheumatoid factor positive |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 116 | Reduced number of B cells |
0 (0.0%) | 3 (17.7%) | 14 (82.4%) |
| 117 | Increased IgE levels |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 118 | Coombs Test Positive |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 119 | (unusual) Epstein-Barr virus infection |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 120 | Hepatitis |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 121 | Urinary incontinence |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 122 | Autoimmune hepatitis |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 123 | Encephalitis |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 124 | Cytomegalovirus infection |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 125 | Immune dysregulation |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
Summary of treatment outcomes
[Considering only Definitive and Possible cases]
| Treatment ⓘ | Responses & clinical indications |
|---|---|
| Immunosuppressive agents | Absent (2) for Polyarthritis; unspecified. Good (2) for Autoimmunity; Granulomatous-lymphocytic interstitial lung disease; unspecified. Mild (1) for Oral ulcer. Moderate (1) for unspecified. Unspecified (1) for Neutropenia |
| Infliximab | Good (1) for unspecified |
| Anti-TNF drug | Good (1) for unspecified |
| Corticosteroids | Mild (1) for Oral ulcer. Moderate (1) for unspecified. Good (1) for Granulomatous-lymphocytic interstitial lung disease. Unspecified (1) for Neutropenia |
| Azathioprine | Absent (1) for unspecified |
| Methotrexate | Absent (1) for Polyarthritis |
| Ustekinumab | Negative/Bad (1) for unspecified. Unspecified (1) for Crohn's disease |
| Prednisolone | Good (1) for Granulomatous-lymphocytic interstitial lung disease |
| Biological agents | Negative/Bad (1) for unspecified. Unspecified (1) for Crohn's disease |
| Monoclonal antibodies | Negative/Bad (1) for unspecified. Unspecified (1) for Crohn's disease |
| Mycophenolate mofetil | Unspecified (1) for Neutropenia |
| Intravenous immunoglobulin therapy | Unspecified (8) for Hypogammaglobulinemia; Immunodeficiency; Panhypogammaglobulinemia; unspecified. Good (6) for Chronic rhinitis; Decreased IgG levels & Recurrent lower respiratory tract infections; Decreased IgG levels & Recurrent upper respiratory tract infection; Hypogammaglobulinemia & Recurrent bronchopulmonary infections; Recurrent upper respiratory tract infection |
| Budesonide | Unspecified (1) for Chronic diarrhea |
| Antibiotics | Moderate (1) for Fever & Oral ulcer |
| Anti-Inflammatory agents | Unspecified (1) for Chronic diarrhea |
| Cyclophosphamide | Good (1) for Autoimmunity |
| Liver transplant | Negative/Bad (1) for Acute hepatic failure |