BACKGROUND: patients with 22q11.2DS may develop severe thrombocytopenic purpura (ITP) and hemolytic anemia (AIHA). There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients.
OBJECTIVE: describe the peculiar B and T subpopulations defects in 22q11DS patients that have developed HA and test if these defects precede the development of HA.
METHODS: We performed a case-control multicenter study. Patients with HA were compared with a control population of 22q11.2DS without hematologic autoimmunity (non-HA). A complete immunological evaluation was performed at diagnosis and at last follow-up including extensive T and B phenotype.
RESULTS: Immunophenotype at last follow-up was available in 23 HA and 45 non-HA patients. HA patients had significantly decreased percentage of naïve CD4+ cells, (26,8% vs 43,2%, p=0,003) and recent thymic emigrants (48,6% vs 80,5%, p=0,046); decreased class-switched B cells (2,0% vs 5,9% p=0,04) and increased naive B cells (83,5% vs 71,4%, p=0,02); increased CD16+/56+ both in absolute number (312 vs 199, p=0,009) and percentage (20,0% vs 13,0%, p=0,03). Immunophenotype was performed in 36 patients (11 HA and 25 non-HA) at diagnosis. Odds ratio (OR) of immune cytopenia were estimated for both CD4 naïve ≤30% (OR 14.0 p=0.002) and for SMB ≤2% (OR 44.0 p=0.01). The estimated survival curves reached statistical significance respectively p=0.0001 and p=0.002.
CONCLUSION: Among 22q11.2DS patients those with HA have characteristic lymphocytes anomalies that appear considerably before HA onset. Systematic immunophenotyping of 22q11.2DS patients at diagnosis is advisable for early identification of patients at risk for this severe complication.
|Journal||Journal of Allergy and Clinical Immunology: In Practice|
|Publication status||E-pub ahead of print - Mar 25 2019|