Table 1.
Description of the main clinical and laboratory characteristics of patients with common variable immunodeficiency included in the study
| P | Sex | Age | Clinical history | CVID group | Igs at diagnosis | Cellular phenotype | PSCv | PTv | Genetic study | IgRT | Immunosuppressant and/or therapy for tumor (last dose date) | Vaccine | Anti-SARS-COV-2 vaccine response (humoral/cellular) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P1 | F | 47 | Autoimmunity. Solid organ tumor | A/L |
IgG: 597 (low) IgA: 84 IgM: 32 (low) |
-LB: 230 cells/µI. Decreased naive and class switched memory B cells. Increased CD21low B cells -LT: 937 cells/µI. Augmented EM phenotype in CD8 + T cells |
No | No | TNFRSF13B* (c.198C > A/p.Cys66Ter, AR/AD, HE) | No | Surgical resection (2020) | BNT162b2 | Yes/Yes |
| P2 | F | 64 | RTI. Solid tumor | A/L |
IgG: 562 (low) IgA: 49 (low) IgM: 90 |
-LB: 192 cells/µI. Increased CD21low B cells -LT: 876 cells/µI. Augmented EM phenotype in CD8 + T cells |
No | No | Negative | SCIG | Surgical resection (2016) | BNT162b2 | Yes/Yes |
| P3 | F | 58 | Giardia infections. RTI. Autoimmunity. Splenectomized | A/L |
IgG: 326 (low) IgA: < 6.6 (low) IgM: 120 |
-LB: 1171 cells/µI. Decreased class switched and marginal zone memory B cells. Increased CD21low B cells -LT: 2049 cells/µI. Augmented EM activated phenotype in CD8 + T cells |
No | No | Negative | SCIG | No | BNT162b2 | Yes/Yes |
| P4 | F | 22 | RTI. Solid organ tumor. Bronchiectasis. Hodgkin lymphoma | A/L |
IgG: 260 (low) IgA: 31 (low) IgM: 160 |
-LB: 18 cells/µI. Increased CD21low B cells. Low isohemagglutinins -LT:1478 cells/µI. Increased EM T cells at the expense of naive lymphocytes |
No | Yes |
CARD11 (c.1528G > A/p.Ala510Thr, AR/AD, HE) VUS |
IVIG |
Bleomycin (2017) Etoposide (2017) Doxorubicin (2017) Cyclophosphamide (2017) Vincristine (2017) Procarbazine (2017) Corticoids (2017) |
BNT162b2 | Yes/No |
| P5 | M | 41 | RTI. Autoimmunity. Splenomegaly. Lymphadenopathies. GLILD. MALT lymphoma | A/L |
IgG: 426 (low) IgA: 44 (low) IgM: 23 (low) |
-LB: 64 cells/µI B cell lymphopenia. Increased CD21low B cells -LT: 1450 cells/µI. Increased EM T cells |
No | No | Negative | SCIG |
Corticoids (2020) Rituximab (2020) |
BNT162b2 | No/Yes |
| P6 | F | 45 | RTI. UTI. C. Jejuni infections. Fungal infections. Otitis. Autoimmunity | A/L |
IgG: 448 (low) IgA: < 6.6 (low) IgM: 25 (low) |
-LB: 20 cells/µI. Low levels of free light-chains and isohemagglutinins -LT: 1427 cells/µI. Th17 bias at the expense of Th1-like T cells |
No | No | NA | No |
Azatioprine (2011) Leflunomide (2011) Etarnecept (2013) Rituximab (2018) Corticoids (currently) Sulfasalazine (currently) |
BNT162b2 | No/Yes |
| P7 | M | 70 | RTI. Splenomegaly. Lymphadenopathies | A/L |
IgG: 534 (low) IgA: < 6.6 (low) IgM: 32 (low) |
-LB: 146 cells/µI -LT: 927 cells/µI. CD4 + lymphopenia |
No | No | NA | IVIG | No | BNT162b2 | Yes/Yes |
| P8 | F | 59 | Bell's palsy. Soft tissue infections. Hepatosplenomegaly | A/L |
IgG: 379 (low) IgA: 56 (low) IgM: 9 (low) |
-LB: 85 cells/µI. Increased CD21low B cells -LT: 776 cells/µI. CD4 + T cell lymphopenia. No Quantiferon-CMV responder |
No | No | NA | IVIG | No | BNT162b2 | No/No |
| P9 | F | 33 | RTI | Inf |
IgG: 521 (low) IgA: 94 IgM: 13 (low) |
-LB: 82 cells/µI. Decreased memory B cells -LT: 743 cells/µI |
NA | NA | NA | IVIG | No | BNT162b2 | Yes/Yes |
| P10 | M | 45 | RTI | Inf |
IgG: 371 (low) IgA: 43 (low) IgM: 121 |
-LB: 22 cells/µI -LT: 1014 cells/µI |
No | No | NA | IVIG | No | BNT162b2 | Yes/Yes |
| P11 | M | 30 | RTI. Zoster. Splenomegaly | Inf |
IgG: 491 (low) IgA: < 6.6 (low) IgM: 25 (low) |
-LB: 211 cells/µI. Decreased naive and class switched memory with increased transitional B cells -LT: 1736 cells/µI. Augmented activated EM phenotype in CD8 + T cells |
No | No | Negative | SCIG | No | BNT162b2 | Yes/Yes |
| P12 | F | 72 | RTI associated with sepsis | Inf |
IgG: 515 (low) IgA: 133 IgM: 26 (low) |
-LB: 249 cells/µI -LT: 1868 cells/µI |
No | No | NA | IVIG | No | mRNA-1273 | Yes/Yes |
| P13 | F | 36 | RTI. Hepatosplenomegaly Lymphadenopathies. Bronchiectasis | A/L |
IgG: 408 (low) IgA: 99 IgM: 15 (low) |
-LB: 208 cells/µI. Decreased class switched and marginal zone memory B cells. Increased transitional B cells. Increased CD21low B cells -LT: 828 cells/µI. Augmented EM phenotype in CD8 + T cell |
No | Yes | Negative | IVIG | No | mRNA-1273 | Yes/Yes |
| P14 | F | 24 | Autoimmunity. Lymphadenopathies | A/L |
IgG: 149 (low) IgA: < 6.6 (low) IgM: 360 (high) |
-LB: 170 cells/µI. Decreased class switched memory with increased CD21Low and transitional B cells -LT: 1001 cells/µI. CD4 + lymphopenia. Augmented EM phenotype in CD8 + T cells |
No | No |
2 ATM variants (c.4060C > A/ p.Pro1354Thr and c.5039C > T/ p.Pro1680Leu, AR, HE) VUS |
IVIG |
Rituximab (2010) Corticoids (currently) |
mRNA-1273 | Yes/Yes |
| P15 | F | 44 | Autoimmunity. Solid tumor | A/L |
IgG: 445 (low) IgA: 18 (low) IgM: 27 (low) |
-LB: 343 cells/µI. Absence of plasmablasts -LT: 948 cells/µI |
No | Yes |
PIK3R1 (c.889G > A/ p.Glu297Lys AR/AD,HE) VUS |
IVIG |
Surgical resection (2019) Corticoids (currently) |
mRNA-1273 | Yes/No |
| P16 | M | 56 | RTI | Inf |
IgG: 595 (low) IgA: 125 IgM: 31 (low) |
-LB: 224 cells/µI -LT: 1287 cells/µI. Augmented activated EM phenotype in CD8 + T cells |
Yes | Yes | NA | No | No | mRNA-1273 | Yes/Yes |
| P17 | F | 60 | RTI | Inf |
IgG: 345 (low) IgA: 115 IgM: 8 (low) |
-LB: 37 cells/µI -LT: 575 cells/µI. Augmented activated EM phenotype in CD8 + T cells |
No | Yes | NA | No | No | mRNA-1273 | Yes/Yes |
| P18 | M | 60 | RTI. Splenomegaly. Cytopenia | A/L |
IgG: 667 (low) IgA: < 6.6 (low) IgM: 15 (low) |
-LB: 63 cells/µI. Decreased naive and class switched memory B cells -LT: 696 cells/µI |
Yes | Yes | NA | SCIG | No | ChAdOx1 | Yes/Yes |
Immunoglobulins appointed in mg/dl. Normality gap: IgG 700–1600 mg/dl; IgA 70–400 mg/dl; IgM 40–230; LB 100–500 cells/µI; LT 850–2250 cells/µI. A/L autoimmune/lymphoproliferative (group); EM effector memory; F female; GLILD granulomatous-lymphocytic interstitial lung disease; HE heterozygosity; Igs immunoglobulin; IgRT immunoglobulin replacement treatment; Inf only infections (group); LB lymphocyte B; LT lymphocyte T; SCIG subcutaneous Immunoglobulin; IVIG intravenous Immunoglobulin; M male; MALT mucosa-associated lymphoid tissue; P patient; PSCv polysaccharide vaccination response; NA not assessed; PTv proteic vaccination response; RTI respiratory tract infections; UTI urinary tract infections; VUS variant of uncertain significance
*Among the genetic variants in this table, this is the only one described that has probably pathogenic according to previous publications [15, 16], online predictors [17], and genome databases [18]