Table 1.
Characteristics of Patients with STIM1 Deficiency.*
| Characteristic | Patient V-1 | Patient V-4 | Patient V-7 |
|---|---|---|---|
| Year of birth | 1991 | 1994 | 2002 |
| Sex | Female | Female | Male |
| STIM1 mutation† | E136X (both alleles) | Not known | E136X (both alleles) |
| Clinical manifestations | |||
| Infection or related symptoms or therapy | Infection with Escherichia coli and Streptococcus pneu-moniae , resulting in sepsis; urinary tract infections; pneumonia; infection with CMV and VZV |
Infection with EBV, enteroviral encephalitis, prolonged diarrhea |
Undocumented sepsis; treatment with IV immune globulin since birth |
| Autoimmune disorder | Hemolytic anemia, thrombocytopenia | Hemolytic anemia, thrombocytopenia | Thrombocytopenia |
| Lymphoproliferative disorder | Lymphadenopathy, hepatosplenomegaly | Lymphadenopathy, hepatosplenomegaly | None |
| Other | Muscular hypotonia, partial iris hypoplasia, abnormal dental enamel |
Muscular hypotonia, partial iris hypoplasia, abnormal dental enamel, nephrotic syn drome |
Muscular hypotonia, partial iris hypo-plasia , abnormal dental enamel, hypoglycemia |
| Follow-up data | Died at 9 yr from HSCT complications | Died at 18 mo from encephalitis | HSCT performed at 15 mo; patient currently alive and well with muscular hypotonia |
| Immunologic features | |||
| Lymphocyte count — ×10−3/µl (normal range) | 2.2 (2.3–5.7) | 7.0 (3.9–9.0) | 3.9 (3.9–9.0) |
| T cell population — % (normal range) | |||
| CD3+ | 83 (56–76) | 55 (49–76) | 63 (49–76) |
| CD4+ | 48 (28–47) | 45 (31–56) | 50 (31–56) |
| CD8+ | 29 (16–35) | 8 (12–24) | 9 (12–24) |
| CD4+CD45RA+ | 24 (53–86) | NM | NM |
| CD4+CD45RA+CD31+ | 14 (43–55) | NM | NM |
| CD4+FOXP3+ | 0.3 (2.5–6.0) | NM | NM |
| Natural killer CD56+CD16+ cells — % (normal range) | NM | NM | 12 (3–15) |
| B-cell CD19+ cells — % (normal range) | 8 (6–35) | 37 (14–37) | 21 (14–37) |
| T-cell proliferation after stimulation — ×10−3 cpm (normal threshold)‡ | |||
| With PHA | 43 (>50) | NM | 7 (>50) |
| With PMA and ionomycin | 26 (>100) | NM | NM |
| With anti-CD3 antibody | 2 (>30) | NM | 0 (>30) |
| With anti-CD3 antibody and interleukin-2 | 46 (>50) | NM | NM |
| With VZV | 0 (>10) | NM | NM |
| With tetanus toxoid | NM | NM | 0.3 (>10) |
| Immunoglobulin — mg/dl (normal range)§ | |||
| IgG | 1700 (900–1480) | 46 (230–623) | 336 (230–623) |
| IgA | 71 (110–260) | 70 (20–86) | 109 (20–86) |
| IgM | 82 (88–180) | 23 (34–136) | 44 (34–136) |
All ranges and thresholds are adjusted for age. Values that are considerably outside the normal range are shown in bold. CMV denotes cytomegalovirus, cpm counts per minute, EBV Epstein–Barr virus, HSCT hematopoietic stem-cell transplantation, IV intravenous, NM not measured, PHA phytohemagglutinin, PMA phorbol 12-myristate 13-acetate, STIM1 stromal interaction molecule 1, and VZV varicella–zoster virus.
DNA samples from Patient V-4 were not available for genotyping. The “X” in “E136X” denotes a premature stop codon.
T cells obtained from Patients V–l and V–7 did not proliferate in response to stimulation with VZV and tetanus toxoid in vitro despite two episodes of chickenpox (in Patient V-l) and one round of vaccination against diphtheria, pertussis, and tetanus 1 month before the testing of the response to recall antigens (in Patient V–7).
The immunoglobulin levels of Patient V-4 were measured after the onset of the nephrotic syndrome.