Table 2.
Patient characteristics
| Patient | Sex | ALPS Subtype | Age at First Abnormal CT (yr) | DlCO Corrected for Hb* (% predicted) | Lung Physiology | Lung CT Patterns | Pathology Findings | Presenting Symptoms | Treatment for Pulmonary Disease | Outcome (yr of follow-up) |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | M | ALPS-U | 21 | 96 | Obstructive† | Bronchiectasis, cyst, nodules not TIB, septal lines | NA | Asymptomatic | Continued on same dose of MMF | No change (18) |
| 2 | M | ALPS-U | 14 | 59 | No significant abnormality | Bronchiectasis, consolidation, GGO, nodules not TIB, septal lines, TIB | Interstitial lymphoplasmacytic infiltrate‡ (TTB) | Asymptomatic | None | No change (12) |
| 3 | M | ALPS-U | 11 | 58 | Restrictive | Bronchiectasis, GGO, nodules not TIB, septal lines, TIB | NA | Asymptomatic | None | No change (27) |
| 4 | M | ALPS-U | 17 | 68 | Restrictive | Bronchiectasis, cyst, GGO, nodules not TIB, septal lines, TIB | Patchy lymphocytic infiltrate‡ (TBB, BAL) | Asymptomatic | Continued on same dose of MMF, given pulse dose steroids | CT-based improvement (27) |
| 5 | F | ALPS-U | 10 | 61 | Restrictive | Bronchiectasis, consolidation, GGO, nodules not TIB, septal lines, TIB | Organizing pneumonia with BOOP-like changes‡ (TBB) | Asymptomatic | Prednisone, azathioprine, MMF | Persistent diffusion defect, 6MWT and CT-based improvement (6) |
| 6 | M | ALPS-U | 15 | 57 | Restrictive† | Bronchiectasis, cavitation, consolidation, GGO, nodules not TIB, septal lines, TIB | Follicular bronchiolitis‡ (TBB) | Asymptomatic | Continued on same dose of MMF and methotrexate, given pulse dose steroids | No change in symptoms, progressive decline in DlCO (24) |
| 7 | F | ALPS-U | 7 | NA | NA | GGO, TIB, nodules not TIB | Follicular bronchiolitis, pneumonitis characterized by inflammation and lymphocytes in bronchioles, BOOP-like changes, EBER-negative‡ (TTB) | Asymptomatic | None | Pulmonary outcome unknown; patient deceased (4) |
| 8 | F | ALPS-FAS | 39 | 72 | No significant abnormality | Bronchiectasis, consolidation, cyst, GGO, nodules not TIB, septal lines, TIB | Granulomatous and chronic inflammation (TTB) | Asymptomatic | None | No change (53) |
| 9 | M | ALPS-FAS | 36 | NA | NA | Cyst, GGO | NA | Asymptomatic | None | No change (47) |
| 10 | M | ALPS-U | 14 | 70 | No significant abnormality | GGO, TIB, nodules not TIB, bronchiectasis | NA | Asymptomatic | Continued on same dose of MMF | No change (16) |
| 11 | M | ALPS-U/STAT3 GOF mutation | 22 | 50 | Restrictive | Bronchiectasis, consolidation, GGO, nodules not TIB, septal lines, TIB | Dense fibrous scar tissue, minimal chronic inflammation (TTB) | Asymptomatic | Continued on same dose of MMF | No change in symptoms, DlCO improved (21) |
| 12 | M | ALPS-U | 14 | 62 | No significant abnormality | GGO, TIB, nodules not TIB, bronchiectasis | NA | Asymptomatic | Continued on same dose of sirolimus | No change in symptoms, CT-based improvement (3) |
| 13 | M | ALPS-U | 30 | 60 | No significant abnormality | Bronchiectasis, consolidation, GGO, nodules not TIB, septal lines, TIB | Mild chronic inflammation of bronchial wall, mild chronic interstitial pneumonitis (TBB) | Asymptomatic | None | No change (8) |
| 14 | F | ALPS-U | 12 | 103 | Obstructive | Bronchiectasis, consolidation, GGO, nodules not TIB, septal lines, TIB | Patchy lymphocytic infiltrate, no evidence of double-negative T cells‡ (TBB, BAL) | DOE | MMF increased | DlCO improved (15) |
| 15 | M | ALPS-U | 6 | NA | NA | GGO, TIB, septal lines | Focally necrotizing granulomatous pneumonitis, interstitial lymphocytic infiltrate, small necrotizing granulomas (TBB) | Asymptomatic | None | NA (4) |
| 16 | M | ALPS-FAS | 22 | 77 | No significant abnormality | Nodules not TIB | NA | Asymptomatic | None | NA (22) |
| 17 | M | ALPS-U | 13 | 41 | Restrictive† | GGO, nodules not TIB, septal lines, TIB | Patchy T-cell–predominant lymphocytic infiltrate‡ (TBB, BAL) | Dyspnea, desaturation on room air | MMF, prednisone | DlCO and symptoms wax and wane (14) |
| 18 | M | ALPS-FASLG | 16 | 64 | No significant abnormality | Bronchiectasis, GGO, nodules not TIB, septal lines, TIB | Nondiagnostic‡ (TBB, BAL) | Asymptomatic | None | No change in symptoms, progressive decline in DlCO (24) |
Definition of abbreviations: ALPS-U = autoimmune lymphoproliferative syndrome with undetermined genetic defect; BAL = bronchoalveolar lavage; BOOP = bronchiolitis obliterans organizing pneumonia; CT = computed tomographic scan; DlCO = diffusing capacity of the lung for carbon monoxide; DOE = dyspnea on exertion; EBER = Epstein-Barr virus–encoded small RNA; GGO = ground-glass opacity; GOF = gain of function; MMF = mycophenolate mofetil; 6MWT = 6-minute walk test; NA = not available; STAT3 = signal transducer and activator of transcription 3; TBB = transbronchial biopsy; TIB = tree-in-bud pattern; TTB = transthoracic biopsy.
One patient was reclassified from ALPS-U to STAT3 gain-of-function mutation.
*
First DlCO measurement was obtained after CT abnormalities were detected.
†
Exertional dyspnea greater than 3% in 6-minute walk test.
‡
Pathology reviewed at the National Institutes of Health.