Table 2.
Clinical and laboratory phenotype of human CARD11 deficiency.
| Mutation | p.Gln945* | p.Phe902_Glu946del Exon 21 del | p.Phe902_Glu946del Exon 21 del | p.Phe902_Glu946del Exon 21 del | p.Cys150* | p.Cys150*+ somatic p.Cys150Leu |
|---|---|---|---|---|---|---|
| Age | 6 months | 9 months | 3 months | 6 months | Birth | 6 months |
| Sex | F | F | F | M | M | F |
| Ethnicity | Central European | Palestinian | Palestinian | Palestinian | Turkish | Turkish |
| Consanguinity | + | + | + | + | + | + |
| Functional Impact | Loss | Loss | Loss | Loss | Loss | Loss then moderate restoration |
| Inheritance | AR | AR | AR | AR | AR | AR |
| Gene Expression | Normal | Truncated | Truncated | Truncated | ↓ | Normal |
| Protein Expression | Truncated | None | None | None | None | Restored |
| INFECTIONS | ||||||
| Pulmonary | + | + | ND | + | + | + |
| Pneumocystis jirovecii | + | + | ND | ND | + | – |
| CMV | – | – | ND | ND | + | + |
| Human metapneumovirus | – | – | ND | ND | – | + |
| Rhinovirus | – | – | ND | ND | – | + |
| Blood | – | – | ND | ND | + | + |
| Staphylococcus aureus | – | – | ND | ND | – | + |
| Enterococcus | – | – | ND | ND | + | + |
| Pseudomonas | – | – | ND | ND | – | + |
| Klebsiella | – | – | ND | ND | + | – |
| Eyes (retina) | – | – | – | – | – | + |
| CMV | – | – | – | – | – | + |
| Meningitis | – | + | – | + | – | – |
| CLINICAL MANIFESTATIONS | ||||||
| Failure to thrive | – | – | + | ND | – | – |
| Eczema | – | – | ND | ND | – | + |
| Erythroderma | – | – | ND | ND | – | + |
| Lymphadenopathy | – | – | ND | ND | – | + |
| Hepatosplenomegaly | – | – | ND | ND | – | + |
| Dyspnea | – | + | ND | ND | – | – |
| Tachypnea | + | – | ND | ND | – | – |
| Microcephaly | – | – | ND | ND | + | + |
| Developmental delay | – | – | ND | ND | + | + |
| Congestive heart failure | – | – | ND | ND | – | + |
| Seizures | – | – | ND | ND | + | – |
| THERAPY | ||||||
| Transplantation | + | + | – | – | – | – |
| Successful | + | + | N/A | N/A | N/A | N/A |
| IVIG | – | + | ND | ND | + | + |
| Anti-microbial prophylaxis | + | + | ND | ND | ND | ND |
| TMP/SMX | + | + | ND | ND | ND | ND |
| IMMUNOSUPPRESSION | ||||||
| Pre-transplantation | + | ND | – | – | – | – |
| Treosulfan | + | ND | – | – | – | – |
| Fludarabine | + | ND | – | – | – | – |
| Alemtuzumab | + | ND | – | – | – | – |
| Post-transplantation | + | ND | – | – | – | – |
| Cyclosporine | + | ND | – | – | – | – |
| Mycophenolate mofetil | + | ND | – | – | – | – |
| Outcome | Alive | Alive | Dead | Dead | Dead | Dead |
| Cause of death | N/A | N/A | Respiratory failure | Respiratory failure | Sepsis | Interstitial pneumonia |
| LYMPHOCYTES | ||||||
| Total CD19 B cells | Normal | Normal | ND | ND | Normal | ↓ then normal |
| Naive | ↓ | ↑ | ND | ND | ND | ND |
| Transitional | ↑ | ↑ | ND | ND | ↑ | ND |
| (Class-switched) memory | ↓ | ↓ | ND | ND | ↓ | ND |
| Total CD3 T cells | Normal | ND | ND | ND | ↑ | ↓ then ↑↑↑ |
| CD4 | Normal | Normal | ND | ND | Normal | ↓ then ↑↑↑ |
| CD4 CD45RA | ↑ | Normal | ND | ND | Normal | Normal then ↓ |
| CD8 | Normal | Normal | ND | ND | ↑ | ↓ then ↑↑↑ |
| CD8 CD45RA | ↑ | Normal | ND | ND | ND | ND |
| Treg | ↓ | ↓ | ND | ND | ↓ | ↓ |
| PROLIFERATION | ||||||
| PHA | ↓ | ↓ | ND | ND | ↓ | ↓ |
| ConA | ↓ | ND | ND | ND | ND | ND |
| PWM | Normal | ND | ND | ND | ND | ND |
| CD3 | ↓ | ND | ND | ND | ND | ND |
| CD3+CD28 | ND | ↓ | ND | ND | ↓ | ↓ |
| IMMUNOGLOBULINS | ||||||
| IgG | ↓ | ↓ | ND | ↓ | ↓ | ↓ |
| IgA | ↓ | ↓ | ND | ↓ | ↓ | ↓ |
| IgM | ↓ | ↓ | ND | ↓ | ↓ | ↓ |
| IgE | ND | ND | ND | ND | Normal | ↑ |
| Specific antibodies | ||||||
| Tetanus | ND | ND | ND | ND | Negative | Negative |
| Pertussis | ND | ND | ND | ND | Negative | Negative |
| Diphtheria | ND | ND | ND | ND | Negative | Negative |
| Haemophilus influenzae B | ND | ND | ND | ND | Negative | Negative |
| References | (18) | (17) | (17) | (17) | (19) | (19) |
Key molecular, immunological, infectious, and pathological findings for all patients with CARD11 deficiency described to date. ND, no data; ↑, increased levels relative to normal range; ↓, decreased levels relative to normal range; +, present; −, absent;
*
premature stop; AR, autosomal recessive; CMV, cytomegalovirus; IVIG, intravenous immunoglobulin; TMP/SMX, trimethoprim/sulfamethoxazole; PHA, phytohemagglutinin; ConA, concanavalin A; PWM, pokeweed mitogen.