In Search for the Missing Link in APECED-like Conditions: Analysis of the AIRE Gene in a Series of 48 Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Molecular Studies
AIRE Gene Screening
2.3. Statistical Analysis
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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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 |
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Fierabracci, A.; Belcastro, E.; Carbone, E.; Pagliarosi, O.; Palma, A.; Pacillo, L.; Giancotta, C.; Zangari, P.; Finocchi, A.; Cancrini, C.; et al. In Search for the Missing Link in APECED-like Conditions: Analysis of the AIRE Gene in a Series of 48 Patients. J. Clin. Med. 2022, 11, 3242. https://doi.org/10.3390/jcm11113242
Fierabracci A, Belcastro E, Carbone E, Pagliarosi O, Palma A, Pacillo L, Giancotta C, Zangari P, Finocchi A, Cancrini C, et al. In Search for the Missing Link in APECED-like Conditions: Analysis of the AIRE Gene in a Series of 48 Patients. Journal of Clinical Medicine. 2022; 11(11):3242. https://doi.org/10.3390/jcm11113242
Chicago/Turabian StyleFierabracci, Alessandra, Eugenia Belcastro, Elena Carbone, Olivia Pagliarosi, Alessia Palma, Lucia Pacillo, Carmela Giancotta, Paola Zangari, Andrea Finocchi, Caterina Cancrini, and et al. 2022. "In Search for the Missing Link in APECED-like Conditions: Analysis of the AIRE Gene in a Series of 48 Patients" Journal of Clinical Medicine 11, no. 11: 3242. https://doi.org/10.3390/jcm11113242