Table 1.
Immunological parameters of patients with typical and atypical EV.
| Disease | Genetic etiology∗ | Clinical phenotypes (affected/total no. of patients) | Expression pattern | T cell counts | T cell function | Other immunological features | Reference |
|---|---|---|---|---|---|---|---|
| Typical EV | AR TMC6/EVER1 | EV | Broad (including keratinocytes and T cells) | Normal | Normal | None | Orth, 2006, 2008; Imahorn et al., 2017 |
| AR TMC8/EVER2 | EV | Broad (including keratinocytes and T cells) | Normal with slightly high proportions for skin-homing subsets | Normal | None | ||
| Atypical EV | AR RHOH deficiency (2 siblings) | Cutaneous viral infections, bronchopulmonary disease, Burkitt lymphoma, disseminated EV-like flat warts (histologically consistent with EV, HPV-3, -12, and -20 on Southern blotting and PCR) | Lymphoid lineage | Naïve CD4+ T-cell lymphopenia, high memory CD4+ and CD8+ T-cell counts, low proportions of skin-homing T-cell subsets | Mildly impaired antigen-induced T-cell proliferation, no anti-CD3-induced proliferation | Normal B cell number and function, normal NK cells | Crequer et al., 2012a |
| AR MST1 deficiency # (1 patient) | Recurrent respiratory infections, candidiasis, disseminated EV-like flat warts (HPV-5 and -15 positive by Southern blotting and PCR), cervical adenopathy, growth retardation | Broad (including keratinocytes and T cells) | Profound CD4+ T-cell lymphopenia (naïve low, memory high), modest naïve and central memory CD8+ lymphopenia, revertant memory CD8+ T-cell counts high | Impaired mitogen (PHA, PMA/Ionomycin)- and antigen (candida, tetanus toxoid, tuberculin)-induced proliferation | Normal B and NK cells, cANCA autoantibodies, high IgA and IgE levels, poor antibody response to several vaccines | Crequer et al., 2012b | |
| AR CORO1A deficiency # (2 siblings) | Bronchiectasis; fatal EBV-positive lymphoma (1/2); mucocutaneous immunodeficiency syndrome with molluscum contagiosum, oral-cutaneous herpetic (HSV-1) ulcers, disseminated EV-like HPV infection (HPV-5 and -17 positive by PCR) and tuberculoid leprosy (1/2) | Broad (including keratinocytes and T cells) | Complete deficiency of naïve CD4+ T cells, high level of double-negative (CD3+CD4-CD8-) gd T cells | Impaired mitogen-induced proliferation, normal antigen-induced proliferation (candida and tetanus toxoid) | T-B +NK+ SCID; absent memory B cells; low NK cell counts, elevated serum IgE, normal serum IgG | Stray-Pedersen et al., 2014 | |
| AR ARTEMIS # p.Leu123Ser (hypomorphic) (1 patient) | Recurrent respiratory and gastrointestinal infections, persistent disseminated flat warts (histologically consistent with EV, no HPV confirmation) | broad (including keratinocytes and T cells) | CD4+ T-cell lymphopenia, CD8+ T-cell counts normal | Impaired mitogen- and antigen-induced proliferation | T low B- leaky SCID, IgM levels normal, IgG levels high, IgA absent, normal NK cell counts | Tahiat et al., 2017 | |
| AR DOCK8 deficiency # (4 families) | Recurrent or severe viral infections associated with cancer, atopic dermatitis, recurrent respiratory or gastrointestinal tract infections, disseminated Molluscum contagiosum; disseminated flat-topped warts (histologically consistent with EV, HPV-5 positive by PCR), eczema, hyperpigmentation, and folliculitis | Broad (including keratinocytes and T cells) | CD4+ T-cell lymphopenia | Normal mitogen-induced proliferation | IgM levels low, IgE levels high, variably impaired specific antibody production, normal CD8+ T-cell and B-cell numbers | Sanal et al., 2012; Liu et al., 2017 | |
| AR RASGRP1 # deficiency (1 patient) | Recurrent ear infections, skin abscesses, chronic non-bloody diarrhea, disseminated warts (histologically consistent with EV, no HPV confirmation), severe failure to thrive, splenomegaly, diffuse lymphadenopathy, fatal EBV-positive B cell lymphoma | Broad (including keratinocytes and T cells) | CD4+ T-cell lymphopenia, CD8+ T-cell counts high | Impaired proliferation in response to mitogen (PHA) and antigen (candida and tetanus toxoid) | Normal NK cell number with reduced function, IgG levels low, IgM levels high | Platt et al., 2017 | |
| AR LCK # c.188-2A>G (3 siblings) | Recurrent bacterial pneumonia; pityriasis-versicolor-like lesions and flat warts on hands, abdomen, legs (histologically consistent with EV, HPV-5, -20, -38 positive by PCR) and histologically confirmed squamous cell carcinomas, fatal in 1 sibling; genital warts (HPV-6 positive by PCR) | Lymphoid lineage | CD4+ T-cell lymphopenia | Not tested | Not tested | Li et al., 2016 | |
| AR TPP2 deficiency (2 siblings) | Evans syndrome (immune thrombocytopenic purpura and autoimmune hemolytic anemia) (2/2); progressive leukopenia (2/2); mild viral infections (1/2); flat, hypopigmented warts (HPV-15 positive by PCR) (1/2), mild developmental delay (1/2) | Broad (including keratinocytes and T cells) | Normal or slightly low CD4+ T lymphocyte counts | Senescent CD8+ T cells (impaired proliferation, enhanced staurosporine-induced apoptosis) | Premature immunosenescence (T and B cells) and antinuclear antibodies; normal IgA and IgE levels; IgG and IgM levels high | Stepensky et al., 2015 |
∗Unless the specific mutation is listed, complete deficiency has been verified experimentally. #Other cases with the same genetic etiology but without EV-like symptoms and beta-HPV infections have been described. AR, autosomal recessive+; SCID, severe combined immunodeficiency.