Table 1.
Clinical and immunological phenotypes of ORAI1- and STIM1-deficient patients
| ORAI1 | STIM1 | |
|---|---|---|
| Gene defect | R91W/R91W | E136X/E136X |
| Chromosome and inheritance | 12q24 homozygous (AR) | 11p15 homozygous (AR) |
| No of Patients | Two (P1, P2) | Three (P3–P5) |
| Gene expression & Ca2+ channel function | ||
| mRNA/protein | Present/present | Absent/absent |
| SOCE/ICRAC | Absent/absent | Absent/not tested |
| Cell types tested | T cells, B cells, fibroblasts | Fibroblasts |
| Immunological manifestations | ||
| Immunodeficiency & infections | P1: BCG infection, rota virus enteritis, Interstitial pneumonia, gastrointestinal sepsis P2: none; HSCT at 4 m |
P3: Pneumonia, urinary tract infections, sepsis (Escherichia coli, Streptococcus pneumoniae); cytomegalo and varizella zoster virus P4: Epstein Barr virus, viral enteritis, enteroviral encephalitis P5: sepsis; HSCT at 15 m |
| Lymphocyte counts | Normal | Normal |
| Lymphocyte subsets | Normal | CD4+ CD25+ Foxp3+ Treg ↓ |
| T cell activation (in vitro) | Proliferation ↓↓ Cytokine production ↓↓ |
Proliferation ↓-↓↓ |
| Antibody production | Normal - ↑ Ig levels (infections), no specific Ab response | Normal Ig levels, no specific Ab response |
| Autoimmunity & lymphoproliferation | No | AIHA (P3, P4), Thrombocytopenia (P3–P5), splenomegaly & lymphadenopathy (P3, P4) |
| Extraimmunological manifestations | ||
| Congenital myopathy | Yes | Yes |
| Ectodermal dysplasia | Enamel dentition defect (Hypocalcified amelogenesis imperfecta) Anhydrosis |
Enamel dentition defect |
| Other | No | P4: Nephrotic syndrome |
| Outcome | P1: Death from sepsis (11 m) P2: Survival after HSCT (now 15 y) |
P3: Death from HSCT complications (9 y) P4: Death from encephalitis (18 m) P5: Survival after HSCT (now 6 y) |
| References | 78,107,110,115,116 | 75 |
Patients lacking STIM1 and functional ORAI1 suffered from similar clinical syndromes comprising immunodeficiency early in life, congenital myopathy, and an enamel calcification defect. STIM1-deficient patients in addition presented with autoimmunity and lymphoproliferation. Ab, antibody; AIHA, autoimmune hemolytic anemia; AR, autosomal recessive; BCG, Bacille Calmette-Guérin; CMV, cytomegalovirus; ICRAC, Ca2+ release-activated Ca2+ (CRAC) channel current; HSCT, hematopoietic stem cell transplantation; m, months; P, patient; SOCE, store-operated Ca2+ entry; y, years.