Type 1 diabetes and associated autoimmune diseases

Table 1 Relevant autoantibodies in type 1 diabetes[10,11,72-75,77,78]

Autoantibody against	Antigen	Sensitivity (%)	Specificity (%)	Normal range	Occurrence
Glutamic acid decarboxylase	Glutamic acid decarboxylase (65 kd)	65-75	99	< 10 IE/mL	70% more common after adolescence
Islet cell	Islet cells	70	99	Negative	80% at diagnosis
Protein tyrosine phosphatase	Tyrosine phosphatase-related islet antigen 2	50-90	99	< 1.0 U/mL	60% at diagnosis
Insulin	Pro-/insulin	74	99	< 0.4 U/mL	50% at diagnosis. First Ab detected in children. Less common after adolescence
Zinc transporter 8	C terminal domain of the zinc transporter 8	65-75	99	< 15 U/mL	Up to 80% at diagnosis
Thyroglobulin	Thyroglobulin	90	99	< 4.1 IU/mL	10%-20% in GD and up to 50% in HT at diagnosis
Thyroperoxidase	Thyroperoxidase	90	99	< 6 IU /mL	70% in GD and 90% in HT at diagnosis
TSH-receptor	TSH-receptor	99	99	< 1.8 IU/mL	More than 90% in GD and 10% in HT at diagnosis
Adrenal cortex	21-hydroxylase and 17 alpha hydroxylase	87	99	Negative	Up to 90% at diagnosis of AD
Transglutaminase IgA	Tissue transglutaminase	90	99	< 20 CU	Common at diagnosis of CD. 6% of patients have an IgA deficiency
Parietal cell	Parietal cells	90	50	Negative	> 90% patients with autoimmune gastritis
Intrinsic factor	Intrinsic factor	80	90	Negative	In 50%-70% of patients with autoimmune gastritis
CCP	CCP	20-25	95	< 20.0 U	In 50%-90% of patients with rheumatoid arthritis
Anti-ro; anti-la	Heterogeneous nuclear ribonucleoproteins	89	99	Negative	70% of patients with Sjögren's syndrome and 50% of patients with lupus erythematosus
Smooth muscle	Smooth muscle	80	99	Negative	In 50%-85% of patients with autoimmune hepatitis
DNA	Double-stranded DNA	65	99	< 30.0 IU/mL	In 50%-70% of patients with systemic lupus erythematosus

CCP: Cyclic citrullinated peptide; GD: Graves‘ disease; Ab: Antibodies; HT: Hashimoto’s thyroiditis; AD: Addison disease; CD: Celiac disease.

Table 2 Autoimmune diseases with corresponding autoantigens and tissue

AID	Tissue	Antigen
Hashimoto’s thyroiditis	Thyroid enzyme/protein	Thyroid peroxidase/thyroglobulin
Graves’ disease	Thyrocytes	TSH receptor
Hypogonadism	Gonads, Leydig-/theca cells	17-hydroxylase, cytochrome-P450 side-chain cleavage
Addison disease	Adrenal cortex enzyme	21-hydroxylase, cytochrome-P450 side-chain cleavage
Hypoparathyroidism	Parathyroid	Ca2+ sensitive receptor
Type A gastritis	Parietal cells	H+, K+-ATPase
Vitiligo	Melanocytes	Tyrosinase
Celiac disease	Small intestine	Transglutaminase, gliadin
Neurodermatitis	Skin	IgE receptor
Psoriasis	Skin	Keratin
Alopecia	Hair follicles	Tyrosine hydroxylase
Urticaria	Skin	IgE receptor FcERI, immunoglobulin E
Sjögren’s Syndrome	Salivary glands	SS-A/Ro and SS-B/La
Rheumatoid arthritis	Synovial membrane	CCP
Autoimmune hepatitis	Liver cells	Smooth muscle, liver-kidney-microsome, soluble liver antigen, liver-pancreas antigen
Systemic lupus erythematosus	Skin, vascular connective tissue	Double-stranded DNA
Crohn’s disease	Gastrointestinal tract	Microbial antigens

AID: Autoimmune diseases; TSH: Thyrotropin or thyroid stimulating hormone; CCP: Cyclic citrullinated peptide.

Table 3 Demographic data

Disease	T1D	T1D + AID
n	131	211
Sex (male/female)	64/67	70/141
Mean age (yr, SD)	33 (± 16)	56 (± 16)
Ethnicity	Caucasian	Caucasian
Mean age at onset (yr, SD)	19 (± 12)	29 (± 18)
Youngest onset (yr)	1	1
Oldest onset (yr)	55	77
Mean duration of T1D (yr, SD)	28 (± 14)	27 (± 16)
Relatives (n)	68	255

T1D: Type 1 diabetes; AID: Autoimmune diseases; Yr.: Year; SD: Standard deviation.