Type 1 diabetes and polyglandular autoimmune syndrome: A review

Table 1 Characteristics of the relevant autoantibodies in type 1 diabetes[125-134]

	Antigen	Sensitivity	Specificity	Percent at onset	Annotation
ICA	Islet cells	70%	99%	70%-90%	Single positivity similar predictive; in combination ≥ 3 increasing risk to approximately 90%; age independent
GADA	Glutamic acid decarboxylase (65 kDa)	65%-75%	99%	70%-80%
IA2A	Tyrosine phosphatase-related islet antigen 2	50%-90%	99%	50%-70%
IAA	Proinsulin/insulin	74%	99%	30%-50%	Inverse correlation with age; measurement prior to insulin therapy required
ZnT8	C terminal domain of the zinc transporter 8	65%-75%	99%	60%-80%	Declines rapidly after onset of T1D

IAA: Insulin autoantibody; IA2A: Tyrosine phosphatase-related islet antigen 2 autoantibodies; ICA: Islet cell autoantibodies; GADA: Glutamic acid decarboxylase autoantibodies; T1D: Type 1 diabetes; ZnT8: Zinc transporter 8.

Table 2 Involvement of family members of patients with type 1 diabetes[5,27,135]

Affected family member	Presence of T1D
First degree relative (general)	5%-6%
Mother	2%
Father	7%
Monozygotic twin	30%-50%
Dizygotic twin	6%-10%

T1D: Type 1 diabetes.

Table 3 Prevalence of associated autoimmunity in patients with type 1 diabetes[15,55,56,60,97,100,136-143]

Associated disease	Patients with type 1 diabetes		General population
	Prevalence of organ-specific Abs	Overt disease	Prevalence of organ-specific Abs	Overt disease
Type 1 diabetes	ICA in 85%-90%	100%	ICA in 1%-3 %	0.1%-1.0%
Hashimoto’s thyroiditis	TPO Abs in 15%-30%	10%-20%	TPO Abs in 2%-10%	0.5%-9.0%
Graves’ disease	TSH-R Abs in 1%-18%	3%-6%	TSH-R Abs in 1%-2%	0.1%-2.0%
Addison’s disease	21-OH Abs in 0.7%-2.0%	0.5%-0.8%	21-OH Abs in 0.6%	0.005%-0.140%
Autoimmune hypophysitis and/or hypopituitarism	Pituitary Abs in 3.6%	0.4%-0.9%	Pituitary Abs in 0.5%	0.24%-0.80%
Autoimmune type A gastritis and pernicious anemia	Gastric parietal cell Abs in 13%-25%	5%-10% (2%-6%)	Gastric parietal cell Abs in 2.5%-12.0%	2% (0.15%-1.00%)
Celiac disease	Transglutaminase Abs in 8%-12%	1%-9%	Transglutaminase Abs in 0.5%-1.0%	0.50%

Abs: Antibodies; ICA: Islet cell antibodies; TPO: Thyroperoxidase; TSH-R: Thyrotropin receptor antibodies; 21-OH: 21 Hydroxylase.

Table 4 Odds ratio of susceptibility genes for autoimmune endocrinopathies[117,144-160]

	T1D	HT	GD	AD
HLA-DR3	3.5	3.7	2-4	5
MICA	1.6	2.5	2	7
PTPN22	1.8	1.6	1.6	1.5
CTLA-4	1.5	5	1.5	1.8

AD: Addison’s disease; CTLA-4: Cytotoxic T lymphocyte antigen 4; GD: Graves’ disease; HLA: Human leukocyte antigen; HT: Hashimoto’s thyroiditis; MICA: MHC class I polypeptide-related sequence A; PTPN22: Protein tyrosine phosphatase non-receptor type 22; T1D: Type 1 diabetes.

Table 5 Polyglandular autoimmune syndromes[13,68,78,161-166]

	PAS Type I	PAS Type II-IV	IPEX
Onset	Childhood	Adulthood	Infancy
Incidence	< 1:100000/yr	1–2:100000/yr	Extremely rare
Male/Female ratio	3:04	1:03	Male >> Female
Genetics	Monogenetic (AIRE)	Polygenetic	X-linked (FOXP3)
Autoantibodies	Anti-interferon-α/ω antibodies 100%, additional Abs	Organ-specific Abs depending on the autoimmune components	ANA (42%) SSA (25%) TG Abs (25%)
Prevalence of T1D	2%-33%	40%-60%	80%
Additional autoimmune endocrine components	Hypoparathyroidism (80%-85%) Addison’s disease (60%-70%) Hypogonadism (12%) Autoimmune thyroid disease (10%)	Autoimmune thyroid disease (70%-75%) Addison’s disease (40%-50%) Hypoparathyroidism (0%-5%) Hypogonadism (0%-3%) Hypopituitarism (0%-2%)	Autoimmune thyroid disease (25%)
Concomitant non-endocrine diseases	Mucocutaneous candidiasis (70%-80%); autoimmune hepatitis; autoimmune gastritis; alopecia areata; vitiligo; keratoconjunctivitis	Autoimmune gastritis; pernicious anemia; neurodermitis; alopecia areata; myasthenia gravis; systemic lupus erythematosus; rheumatoid arthritis; autoimmune hepatitis	Malabsorption; autoimmune skin diseases; multiple sclerosis

Abs: Antibodies; AIRE: Autoimmune regulatory gene; ANA: Anti-nuclear antibodies; FOXP3: Forkhead box protein P3; IPEX: Immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome; PAS: Polyglandular autoimmune syndrome; TG: Transglutaminase; T1D: Type 1 diabetes.