Table 1.
Clinical and immunological features of CARMIL2 patients.
| F1P1 | F1P2 | F1P3 | F2P1 | F2P2 | F3P1 | F3P2 | Normal range | |
|---|---|---|---|---|---|---|---|---|
| Age (years) | 13 | 9 | 29 | 34 | 28 | 12 | 4 | |
| Sex | F | M | M | F | F | M | M | – |
| Onset of illness | 3 years | 5 years | 1 year | 2 years | 9 years | 3 months | 2 weeks | – |
| Age at diagnosis | 10 | 8 | 28 | 34 | 28 | 11 | 3 | – |
| Eczema | Y | Y | Y | No | Y | Y | Y | – |
| Recurrent skin abscesses | Y | Y | Y | Y | Y | Y | Y | – |
| Chest infection | No | No | Y | Y | Y | Y | Y | – |
| Bronchiectasis | No | No | Y | Y | Y | Y | No | – |
| Chronic diarrhea | No | No | No | No | No | No | Y | – |
| Other clinical presentations | Dysphagia, esophageal stenosis, chronic active esophagitis, and candidiasis | Dysphagia and chronic active esophagitis | Dysphagia, chronic active esophagitis, Schatzki ring, and hiatus hernia | Dysphagia and Candida esophagitis | Pneumonectomy | Not done | Dysphagia and eosinophilic esophagitis Severe colitis and crypt abscesses |
|
| EBV PCR (copies/ml) | ND | ND | 57,260 | 35,460 | ND | ND | ND | |
| Other infections | Skin Staphylococcus aureus Candida albicans esophagitis |
Skin S. aureus | Skin S. aureus | C. albicans esophagitis | Dental | Skin S. aureus Warts Scalp fungal infection (Aspergillus niger) Chronic suppurative otitis Media anterior Nasal vestibulitis Cervical lymphadenitis |
Chronic suppurative otitis media Warts Scalp fugal infection |
|
| Other clinical presentations | Suspected hydatid cyst (negative biopsy) | Food allergy, asthma, and allergic rhinitis | Asthma and food allergy | |||||
| WBC (109/L) | 6.6 | 6.46 | 8.6 | 6.23 | 4.07 | 17.5 | 17.1 | a |
| Neutrophils (109/L) | 3.2 | 1.95 | 6.02 | 4.48 | 2.2 | 6.3 | 5.9 | a |
| Lymphocytes (109/L) | 2.6 | 3.82 | 1.98 | 1.13 | 1.38 | 6.5 | 7.2 | a |
| Eosinophils (109/L) | 0.31 | 0.25 | 0.49 | 0 | 0 | 3.2 | 2.2 | a |
| Monocytes (109/L) | 0.39 | 0.45 | 0.03 | 0.57 | 0.46 | 1.5 | 1.6 | a |
| Hemoglobin (g/L) | 115 | 114 | 121 | 100 | 130 | 140 | 114 | b |
| Platelet | 259 | 346 | 331 | 265 | 203 | 434 | 808 | 150–450 109/L |
| CD3+ | 1,839 | 3,758 | 1,689 | 1,202 | 1,530 | 2,578 | 2,944 | c |
| CD3+/CD4+ | 1,161 | 2,131 | 761 | 623 | 876 | 1,307 | 2,234 | c |
| CD3+/CD8+ | 547 | 1,440 | 740 | 552 | 605 | 1,088 | 655 | c |
| CD19+ | 367 | 843 | 423 | 46 | 10 | 947 | 1,506 | c |
| CD16+/CD56+ | 333 | 194 | 21 | 31 | 21 | 87 | 527 | c |
| CD3 CD45RA % | 56 | 71 | ND | 48 | 39 | ND | ND | – |
| CD4 CD45RA % | 44 | 47 | ND | 31 | 23 | ND | ND | – |
| CD3 CD45R0 % | 12 | 7 | ND | 34 | 43 | ND | ND | – |
| CD4 CD45RO % | 8 | 5 | ND | 22 | 36 | ND | ND | – |
| IgG (g/L) | 15.3 | 10.4 | 14.9 | 6.8 | 10.4 | 11.1 | 5.83 | d |
| IgA (g/L) | 2.87 | 1.6 | 5.17 | <0.50 | 2.77 | 3.25 | 2.21 | d |
| IgM (g/L) | 2.52 | 1.48 | 1.69 | 0.29 | 3.74 | 1.72 | 1.00 | d |
| IgE (KU/L) | <2 | 44 | 1,153 | <2 | <2 | >5,000 | <2 | d |
| Tetanus toxoid IgG (mg/L) (prevaccination) | 2.17 | ND | 8 | ND | 0.59 | 0.48 | 0.85 | |
| Tetanus toxoid IgG (mg/L) (postvaccination) | 2.8 | ND | 10 | ND | 0.7 | 0.68 | 0.35 | |
| Tetanus toxoid IgG1 (mg/L) (prevaccination) | <0.67 | ND | 6.5 | <0.67 | <0.67 | ND | ND | |
| Tetanus toxoid IgG1 (mg/L) (postvaccination) | <0.67 | ND | 9.2 | <0.67 | <0.67 | ND | ND | |
| Pneumococcal cap polysaccharide IgG (mg/L) (prevaccination) | 90 | ND | 90 | 12.3 | 160 | 46.9 | <3.3 | – |
| Pneumococcal cap polysaccharide IgG (mg/L) (postvaccination) | >270 | 124 | >270 | 8.7 | >270 | 202 | 10.3 | |
| Pneumococcal cap polysaccharide IgG2 (mg/L) (prevaccination) | ND | ND | 35 | 8.1 | 82 | ND | ND | |
| Pneumococcal cap polysaccharide IgG2 (mg/L) (postvaccination) | ND | 51 | >90 | 4.87 | >90 | ND | ND | |
| PHA (proliferation index) | 4,560–86,042 (3–64%) | 14,696 (11%) | 4,114 (2%) | 33,735 (29%) | 1,700 (2%) | 62,748 (34%) | ND | 94,935–171,149 CPM |
| Con A (proliferation index) | 20,476–117,727 (17–151%) | 30,642 (37%) | 31,984 (26%) | 51,923 (60%) | 6,665 (8%) | 22,916 (22%) | ND | 78,011–133,442 CPM |
| Tetanus toxoid (proliferation index) | 1,018 (1%) | ND | 337 (1%) | 272 (1%) | ND | ND | ND | – |
| Candida (proliferation index) | 883 (10%) | ND | 1,397 (16%) | 902 (3%) | ND | ND | ND | – |
| CARMIL2 mutation | L846Sfs*36 | L846Sfs*36 | L846Sfs*36 | L846Sfs*36 | L846Sfs*36 | R50T | R50T | |
| Diagnosis method | WES | Targeted PCR | Targeted PCR | Genotyping and PCR | Genotyping and PCR | Genotyping and PCR | Genotyping and PCR |
aNormal references for white blood cells counts (109/L): for children 4–8 years, WBC: 5–14.5, neutrophils: 1.6–7.8, lymphocytes: 1.4–6.9, eosinophils: 0–0.43, and monocytes: 0.43–0.86, for children 9–12 years, WBC: 4.5–13.5, neutrophils: 1.4–8.2, lymphocytes: 1.2–6.4, eosinophils: 0–0.4, and monocytes: 0.40–0.8, for children 13–18 years, WBC: 4.5–13, neutrophils: 1.5–8.3, lymphocytes: 1.1–5.8, eosinophils: 0–0.39, and monocytes: 0.39–0.7, and for adults, WBC: 4.5–11, neutrophils: 1.6–7.2, lymphocytes: 1–4.8, eosinophils: 0–0.33, and monocytes: 0.33–0.6.
bNormal references for hemoglobin (g/L): 2–6 years: 115–155, 6–12 years: 115–155, 12–18 years: 130–160, and adults: 135–175.
cNormal references for lymphocytes markers for children 6–13 years of age: CD3: 1,700–1,900/mm3, CD3+/CD4+: 800–1,700/mm3, CD3+/CD8+: 700–1,000/mm3, and CD19+: 400–800/mm3, and CD16+/CD56+: 200–400/mm3. For 18–44 years of age: CD3: 782–2,834/mm3, CD3+/CD4+: 322–1,750/mm3, CD3+/CD8+: 338–1,086/mm3, CD19+: 67–555/mm3, and CD16+/CD56+: 200–400/mm3.
dNormal references for immunoglobulins: IgG (g/L): 1–6 years: 3.5–12.5, 6–12 years: 6.1–15.7, and 12 years adult: 7–16. For IgA (g/L): 3–6 years: 0.2–1, 6–12 years: 0.5–2, and 12 years adult: 0.4–2.3. For IgM (g/L): 3–9 years: 0.43–2.1, 9–12 years: 0.52–2.4, and 12 years adult: 0.4–2.3. For IgE (KU/L): 4–6 years: 8–250, 7–18 years: 8–350, adult: 5–500.
Proliferation index calculated as compared with two healthy control samples.
WBC, white blood cell count; EBV: Epstein–Barr virus; ND, not done; PHA, phytohemagglutinin T cell activation.