Table 1.
Clinical and immunological characteristics of APECED-like patients.
| Patient | Gender | Age at Referral (Years) |
Diseases | Auto Abs |
AIRE Gene Pattern * |
|---|---|---|---|---|---|
| 1 | M | 5.42 | Multiple allergies (5), bronchiectasis (5), asthmatic bronchitis (5), hyper IgE (5), alopecia (10), CMC (10) | TgAbs, TPOAbs, IAA, IA2Abs, TRGAbs, ASCA neg; AMA, ASMA pos | het. S278R |
| 2 | F | 3.5 | Cognitive retardation (1), CMC (3), arthralgia (3), congenital hypothyroidism (3), bronchiolitis (6), Behcet’s disease (11), very early onset inflammatory bowel disease (VEO-IBD) | TgAbs, TPOAbs, ANCA, ASCA, ENA, dsDNAAbs neg; ANA pos | het. S278R |
| 3 | M | 6.19 | Selective IgA deficiency (6), Crohn’s disease (6), arthralgia (7), T1D (9), pharmacological polyallergy (12) | IAA, IA2Abs, GADA, TRGAbs, anti-adrenal Abs, ANA, ANCA, dsDNAAbs neg | het. S278R het. R471C het. IVS9+6 G>A |
| 4 | M | 3.7 | Arthralgia (1), HT (4), recurrent fever episodes (4), selective IgA deficiency (4), vitiligo (5) | IAA, IA2Abs, GADA, TRGAbs, 21OHAbs, dsDNAAbs neg; TgAbs, TPOAbs, ANA pos |
het. IVS9+6 G>A |
| 5 | F | 5.91 | Bronchopneumopathy (5), arthralgia (6), combined immunodeficiency (7), hepatopathy (7), mucociliary dyskinesia (7), eczematous dermatitis (11) | TgAbs, TPOAbs, ANCA, ASCA neg; IAA, IA2Abs, GADA, ANA, dsDNAAbs pos |
het. IVS9+6 G>A |
| 6 | M | 3.57 | Atopic dermatitis (3), combined immunodeficiency (4), CMC (4) | TgAbs, TPOAbs, IAA, IA2Abs, GADA, TRGAbs, dsDNAAbs neg; ANA, ENA, RoAbs, SCL70Abs, LaAbs, SMAbs, RNPAbs, JO1Abs pos |
het. S278R het. IVS9+6 G>A |
| 7 | F | 1.83 | CMC (1), pseudohypoparathyroidism (4), psychomotor retardation (4), coordination disorder (5), congenital onychopathy (12), pityriasis capitis (12), subclinical HT (12) | TgAbs, TPOAbs, ANCA, dsDNAAbs, PM/Scl 100 Abs neg; ANA pos |
WT |
| 8 | M | 7.83 | Vitiligo (10), HT (10), inhalants allergy (10), selective IgA deficiency (12) | TRGAbs, anti-gliadin Abs, EMA, APCA, AMA, ANA, ANCA, ASCA, ENA, dsDNAAbs neg; TgAbs, TPOAbs pos |
WT |
| 9 | M | 4.29 | Candidiasis, alopecia areata (4), subclinical HT (4) (familiarity for HT and T1D) |
TgAbs, TPOAbs, IAA, IA2Abs, GADA, TRGAbs, APCA, ANA, ANCA, ENA neg | het. S278R |
| 10 | F | 2.16 | Childhood obesity (6), CMC (9), recurrent infections (9), T1D (9), preclinical hypoparathyroidism, het. MTHFR C677T homocysteine 9 mutation (9), leukopenia (10) |
TgAbs, TPOAbs, anti-TSH-receptor Abs, TRGAbs, anti-gliadin Abs, ANA, anti-cardiolipin Abs, anti-beta2 glycoprotein Abs neg; IAA, GADA pos |
WT |
| 11 | F | 8.3 | Tubulointerstitial nephritis (4), polyallergy (urticaria and food allergy) (9), chronic renal failure (10), frequent asthma episodes (9), bronchopneumopathy with pulmonary bronchiectasis, hypereosinophilia (9), chronic pancreatitis (10) | ANA, aPLAbs neg; ANCA, ASCA, MPOAbs, anti-cardiolipin Abs pos |
WT |
| 12 | F | 10.99 | Alopecia (few months), HT (9), CMC, bronchitis, asthma, urinary tract infections, food allergies, failure to thrive, hypogammaglobulinemia, eczema, vitiligo, chronic gastritis, morphea | TgAbs, TPOAbs neg | WT |
| 13 | M | 11.18 | Addison’s disease, frequent infections, HT | Diabetes-related Abs, anti-gliadin Abs neg; TgAbs, TPOAbs, 21OHAbs pos |
het. S278R |
| 14 | M | 11.18 | CMC, HT, autoimmune pancytopenia | TgAbs, TPOAbs pos | WT |
| 15 | F | 7.03 | Alopecia (7), recurrent infections | TgAbs, TPOAbs, IAA, IA2Abs, GADA, anti-adrenal Abs, ENA, ASMA, ARA, APCA, ANCA, dsDNAAbs, LKMAbs, LC1Abs, anti-ribosome Abs neg; ANA pos |
WT |
| 16 | F | 10.51 | HT (11), T1D (11), CMC | TPOAbs, IA2Abs, TRGAbs neg; TgAbs, IAA, GADA pos |
WT |
| 17 | F | 5.71 | Turner syndrome, alopecia (3), HT, nail mycosis, cheilitis | TgAbs, TPOAbs pos | het. IVS9+6 G>A |
| 18 | M | 2.8 | Alopecia (3), recurrent respiratory infections, overweight (5) | TgAbs, TPOAbs, IAA, GADA, TRGAbs, APCA, anti-adrenal Abs, AMA, ANA, ARA, LC1Abs, LKMAbs, anti-ribosome Abs neg; IA2Abs, ASMA, ENA pos |
WT |
| 19 | F | CMC, HT, autoimmune hypophysitis | WT | ||
| 20 | M | 9.06 | Alopecia (8), CVID (10), allergic rhinitis (10), onychodystrophy (12), palmar-plantar psoriasis (12), lactose intolerance (15) [54] |
TgAbs, TPOAbs, IAA, IA2Abs, GADA, APCA, ANA, ASCA, ASMA, LKMAbs, dsDNAAbs, ENA, AMA, LC1Abs, anti-ribosome Abs, SCL70Abs neg |
het. S250C |
| 21 | M | 5.57 | Hypoparathyroidism (12) | TgAbs, TPOAbs, IAA, IA2Abs, GADA, 21OHAbs neg |
het. S278R het. IVS9+6 G>A |
| 22 | F | 4.66 | T1D (7) | TgAbs, IA2Abs, TRGAbs neg; GADA pos | het. S278R het. IVS9+6 G>A |
| 23 | M | 2.31 | T1D (2), linguistic retardation (2), celiac disease (21) | TgAbs, TPOAbs neg; TRGAbs pos | het. S278R het. IVS9+6 G>A |
| 24 | F | 2.34 | Congenital cataract, growth retardation (5), HT (5), autoimmune haemolytic anemia (7), juvenile idiopathic arthritis (9), A20 haploinsufficiency (16) | IAA, IA2Abs, APCA, anti-adrenal Abs, AMA, ANCA, ASMA, ARA, dsDNAAbs, LKMAbs, LC1Abs, anti-ribosome Abs neg; TgAbs, TPOAbs, GADA, ANA, ENA pos |
het. S278R het. IVS9+6 G>A |
| 25 | F | 3.72 | T1D, HT (21), vitiligo (21) | Anti-TSH-receptor Abs, IA2Abs, GADA, TRGAbs, anti-adrenal Abs neg; TgAbs, TPOAbs, IAA pos |
het. S278R het. IVS9+6 G>A |
| 26 | F | 4.81 | T1D, Down’s syndrome, Basedow’s disease (32) | TgAbs, TPOAbs, TRGAbs, APCA, anti-adrenal Abs, AMA, ARA, LKMAbs, LC1Abs, anti-ribosome Abs neg; ASMA pos |
het. S278R |
| 27 | F | 11.25 | HT, celiac disease | IAA, IA2Abs, GADA, TRGAbs neg; TgAbs, TPOAbs pos |
het. S278R |
| 28 | F | 12.43 | Alopecia areata (5), parapsoriasis (12), HT (12), mycosis fungoides (13) | het. S278R | |
| 29 | M | 8.41 | Isolated hypoparathyroidism (8) | TgAbs, TPOAbs, TRGAbs, anti-adrenal Abs neg | het. S278R |
| 30 | F | 5.78 | Alopecia (6), onychodystrophy (13) | TgAbs, TPOAbs, IAA, IA2Abs, TRGAbs, APCA, anti-adrenal Abs, AMA, ASMA, ARA, LKMAbs, LC1Abs, anti-ribosome Abs neg; GADA, ANA pos |
het. S278R |
| 31 | F | 10.91 | Primary hypoparathyroidism | het. S278R | |
| 32 | M | 10.08 | Hypoparathyroidism | het. S278R | |
| 33 | F | Addison’s disease, vitiligo | het. S278R het. IVS9+6 G>A |
||
| 34 | F | 14.35 | Central hypoadrenalism (15), HT (15), bronchiectasis (15), CIDP (21) | IAA, GADA, ANA, ANCA neg; TgAbs, TPOAbs pos |
WT |
| 35 | F | 1 | Early menarche from ovarian cyst (9), alopecia (16), HT (17), subclinical hypoadrenalism (17) | TgAbs, TRGAbs, APCA, anti-adrenal Abs, AMA, ASMA, ARA, LKMAbs, LC1Abs, SLA/LPAbs, Sp100Abs, gp210Abs, anti-cardiolipin Abs neg; TPOAbs, ANA pos |
het. S278R |
| 36 | F | Hypoparathyroidism, Addison’s disease, secondary ovarian failure | WT | ||
| 37 | F | 1 | Alopecia (3), HT (7) | TgAbs, IAA, IA2Abs, TRGAbs, APCA, anti-adrenal Abs, AMA, ASMA, ARA, LKMAbs, LC1Abs, anti-ribosome Abs, anti-cardiolipin Abs neg; TPOAbs, GADA, ANA pos |
het. S278R |
| 38 | F | 6.15 | Alopecia (1), nail dystrophy, HT (5), allergic rhinitis (11), arthralgia (11), recurrent infections in pediatric age |
IAA, GADA, TRGAbs, APCA, ANCA, ASMA, ARA, dsDNAAbs, LKMAbs, anti-ribosome Abs neg; TgAbs, TPOAbs, IA2Abs, ANA pos |
het. IVS9+6 G>A |
| 39 | M | 3.84 | T1D, GH deficit, HT, autoimmune leukopenia | TRGAbs, anti-adrenal Abs neg; TgAbs, TPOAbs pos |
het. IVS9+6 G>A |
| 40 | F | 15.42 | Addison’s disease, HT, celiac disease (4) | TgAbs, TPOAbs, IAA, IA2Abs, GADA, APCA, ANA, AMA, ASMA, LKMAbs, ARA, LC1Abs, anti-ribosome Abs neg; TRGAbs, anti-adrenal Abs pos |
WT |
| 41 | M | alopecia, HT, celiac disease | IAA, IA2Abs, GADA, anti-adrenal Abs, dsDNAAbs, aPLAbs, anti-cardiolipin Abs neg; TgAbs, TPOAbs, TRGAbs, ANA, ANCA pos |
het. S278R | |
| 42 | F | Addison’s disease, HT, psoriasis | WT | ||
| 43 | F | 7.97 | Hypoadrenalism (8), hypothyroidism (10) | IAA, IA2Abs, GADA, TRGAbs, AMA, ASMA, ARA, LKMAbs, LC1Abs, anti-ribosome Abs neg; TgAbs, TPOAbs, APCA, anti-adrenal Abs pos |
WT |
| 44 | F | 5.64 | Celiac disease (5), T1D (7), HT (7) | TgAbs, TRGAbs neg; TPOAbs, IAA, IA2Abs, GADA pos | WT |
| 45 | F | 5.19 | T1D (4), autoimmune hepatitis (5), HT (5) | TPOAbs, TRGAbs, APCA, ANA, AMA, ASMA, ARA, ANCA, LKMAbs, LC1Abs, anti-ribosome Abs neg; TgAbs pos |
WT |
| 46 | F | 1.8 | T1D (2), celiac disease (3), autoimmune hepatitis (13) | TgAbs, TPOAbs, TRGAbs, APCA, ANCA, ANA, AMA, ASMA, ARA, LKMAbs, LC1Abs, anti-ribosome Abs neg; IAA, IA2Abs, GADA pos |
WT |
| 47 | F | 11.71 | Arthralgia (4), psoriasis (6), HT (9), T1D (9), gastritis (12) | TgAbs, TRGAbs, APCA, anti-adrenal Abs, dsDNAAbs, AMA, ASMA, ARA, ASCA, LKMAbs, LC1Abs, anti-ribosome Abs neg; TPOAbs, ANA, ANCA pos |
WT |
| 48 | F | 14.77 | Addison’s disease, MERS | IAA, IA2Abs, GADA, APCA, ANA, ENA, AMA, ASMA, ARA, LKMAbs, LC1Abs, aPLAbs, anti-cardiolipin Abs, anti-ribosome Abs, anti-beta2 microglobulin Abs neg; TRGAbs, anti-adrenal Abs pos |
het. S278R |
* Mutations and polymorphisms; WT: Wild Type; het: heterozygous; NT: not tested; neg: negative; pos: positive; GH: growth hormone; MERS: mild encephalitis/encephalopathy with reversible splenial lesion. 21OHAbs: 21OH hydroxylase Abs; JO1Abs: histidyl-tRNA synthetase Abs; SCL70Abs: topoisomerase I Abs; SSA/Ro Abs: anti-Sjögren’s-syndrome-related antigen A Abs; SSB/LA Abs: anti-Sjögren’s-syndrome-related antigen B Abs; SMAbs: anti-Smith Abs; PM/Scl 100 Abs: polymyositis (PM)/Scl-100 Abs; RNPAbs: anti-U1 ribonucleoprotein Abs; ASCA: anti-Saccharomyces cerevisiae Abs; MPOAbs: anti-myeloperoxidase Abs; LC1Abs: liver cytosol Type 1 Abs; aPLAbs: anti-phospholipids Abs; SLA/LPAbs: antibodies against soluble liver antigen/liver-pancreas; Sp100Abs: anti-Sp100 Abs; gp210Abs: anti-glycoprotein-210 Abs. SNPs: single-nucleotide polymorphisms. In brackets, age of disease onset of symptoms is shown.