Clinical phenotype of patients with PTPN2 mutations
| . | Family A . | Family B . | Family C . | Family D . | Family E . | Family F . | |
|---|---|---|---|---|---|---|---|
| Patient | A1 (Proband) | A2 (Father) | B1 (Proband) | C1 (Proband) | D1 (Proband) | E1 (Proband) | F1 (Proband) |
| Gender | F | M | F | F | F | F | M |
| Genotype | c.1209delT (p.Phe403Leufs*25) | c.1209delT (p.Phe403Leufs*25) | c.293G>A (p.Trp98*) | c.866G>A (p.Trp289Ter) | c.70-2A>T (p.Glu24Metfs*20) | c.376T>A (p.Tyr126Asn) | c.647G>C (p.Cys216Ser) |
| Age at onset (years) | 5 | 9 | 6 | Infancy | Infancy | 8 | |
| Clinical features | |||||||
| Autoimmune manifestations | Lupus (renal, cutaneous, hematological, hepatitis) | Asymptomatic | Evans syndrome | Evans syndrome | ITP Common variable immune deficiency | Evans syndrome, autoimmune neutropenia Hashimoto thyroiditis Interstitial pneumonitis Mild cognitive impairment | Evans syndrome (leuco-neutropenia and thrombopenia) Recurrent mouth aphthae Pediatric psychiatric disorders |
| Clinical lymphoproliferation | No | No | No | No | Yes (lymphoid hyperplasia) | Yes (splenomegaly) | No |
| Metabolic disorders | No | No | No | No | No | No | No |
| Growth | Normal | na | na | na | na | na | No |
| Infections | No | No | Yes (recurrent otitis) | No | Yes (recurrent pneumonitis) | No | Rare |
| Therapy | CS, HC, AZA | No | Intermittent Ig | CS, intermittent Ig, VIN, COL, AZA | Intermittent Ig | SIR, relayed by AZA | Antibiotic prophylaxis, AZA |
| Laboratory values | |||||||
| Antibodies (UA/ml) | ANA+ Anti double-stranded DNA and ENA-Anti B2Gp1+ Anti C1q+ Coombs: + | na Coombs: + | ANA+ Coombs: + | ANA+ ANCA+ Coombs: + | na Coombs: + | Anti-HLA I Coombs: + | ANA+ Coombs: + |
| Complement (g/L; normal range) | Lowered | Normal | Normal | na | na | na | Normal |
| Platelet antibodies | Yes | na | Yes | Yes | na | Yes | Yes |
| Type 1 IFN | Positive (7.3) | Negative | na | na | na | na | na |
| Ig | Normal Type III cryoglobulinemia | Inc. IgG Normal IgA and IgM | Normal | Normal IgG and IgA Dec. IgM (0.39) | Dec. IgG, IgA, IgM | Normal | Normal IgG, IgM Dec. IgA, IgG2 partial deficiency |
| Immunophenotyping | Inc. Treg | Normal | Normal Treg Dec. TCD4+; Th1, Th2, Th17; NK Inc. Tfh, auto-reactive B cells | Global lymphopenia, predominant on TCD4+ and NK | TCD4+ moderate lymphocytosis Dec. memory B cells Inc. auto-reactive B cells | Inc. naive B cells Inc. B cells CD21 low | Mild CD4 T and NK lymphopenia, deficiency in switched memory B cells; significant excess of double-negative T cells (TCRab CD8− CD4−) |
| . | Family A . | Family B . | Family C . | Family D . | Family E . | Family F . | |
|---|---|---|---|---|---|---|---|
| Patient | A1 (Proband) | A2 (Father) | B1 (Proband) | C1 (Proband) | D1 (Proband) | E1 (Proband) | F1 (Proband) |
| Gender | F | M | F | F | F | F | M |
| Genotype | c.1209delT (p.Phe403Leufs*25) | c.1209delT (p.Phe403Leufs*25) | c.293G>A (p.Trp98*) | c.866G>A (p.Trp289Ter) | c.70-2A>T (p.Glu24Metfs*20) | c.376T>A (p.Tyr126Asn) | c.647G>C (p.Cys216Ser) |
| Age at onset (years) | 5 | 9 | 6 | Infancy | Infancy | 8 | |
| Clinical features | |||||||
| Autoimmune manifestations | Lupus (renal, cutaneous, hematological, hepatitis) | Asymptomatic | Evans syndrome | Evans syndrome | ITP Common variable immune deficiency | Evans syndrome, autoimmune neutropenia Hashimoto thyroiditis Interstitial pneumonitis Mild cognitive impairment | Evans syndrome (leuco-neutropenia and thrombopenia) Recurrent mouth aphthae Pediatric psychiatric disorders |
| Clinical lymphoproliferation | No | No | No | No | Yes (lymphoid hyperplasia) | Yes (splenomegaly) | No |
| Metabolic disorders | No | No | No | No | No | No | No |
| Growth | Normal | na | na | na | na | na | No |
| Infections | No | No | Yes (recurrent otitis) | No | Yes (recurrent pneumonitis) | No | Rare |
| Therapy | CS, HC, AZA | No | Intermittent Ig | CS, intermittent Ig, VIN, COL, AZA | Intermittent Ig | SIR, relayed by AZA | Antibiotic prophylaxis, AZA |
| Laboratory values | |||||||
| Antibodies (UA/ml) | ANA+ Anti double-stranded DNA and ENA-Anti B2Gp1+ Anti C1q+ Coombs: + | na Coombs: + | ANA+ Coombs: + | ANA+ ANCA+ Coombs: + | na Coombs: + | Anti-HLA I Coombs: + | ANA+ Coombs: + |
| Complement (g/L; normal range) | Lowered | Normal | Normal | na | na | na | Normal |
| Platelet antibodies | Yes | na | Yes | Yes | na | Yes | Yes |
| Type 1 IFN | Positive (7.3) | Negative | na | na | na | na | na |
| Ig | Normal Type III cryoglobulinemia | Inc. IgG Normal IgA and IgM | Normal | Normal IgG and IgA Dec. IgM (0.39) | Dec. IgG, IgA, IgM | Normal | Normal IgG, IgM Dec. IgA, IgG2 partial deficiency |
| Immunophenotyping | Inc. Treg | Normal | Normal Treg Dec. TCD4+; Th1, Th2, Th17; NK Inc. Tfh, auto-reactive B cells | Global lymphopenia, predominant on TCD4+ and NK | TCD4+ moderate lymphocytosis Dec. memory B cells Inc. auto-reactive B cells | Inc. naive B cells Inc. B cells CD21 low | Mild CD4 T and NK lymphopenia, deficiency in switched memory B cells; significant excess of double-negative T cells (TCRab CD8− CD4−) |
M: male; F: female; ITP: idiopathic thrombocytopenic purpura; AIHA: autoimmune hemolytic anemia; ENA: extractable nuclear antigen antibodies; GP: glycoprotein; LB: B lymphocytes; AZA: azathioprine; CS: corticosteroids; HC: hydroxychloroquine; VIN: vinblastine; COL: colchicine; SIR: sirolimus; na: nonavailable; Inc.: increased; Dec.: decreased.