Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients

Table 1 Demographic characteristics of the study population

	Total	Male	Female	Age (yr)
PBC probands	44	4 (9.1)	40 (90.9)	58.8 ± 11.8
PBC FDRs	101	45 (44.6)	56 (55.4)	40.8 ± 17.9
Parents	9 (8.9)	5 (55.6)	4 (44.4)	72.8 ± 8.8
Children	69 (68.3)	30 (43.5)	39 (56.5)	31.3 ± 10.6
Siblings	23 (22.8)	10 (43.5)	13 (56.5)	56.7 ± 10.7
AIH-1 probands	11	2 (18.2)	9 (81.8)	48.8 ± 22.0
AIH-1 FDRs	21	12 (57.1)	9 (42.9)	37.2 ± 14.0
Parents	3 (14.3)	1 (33.3)	2 (66.7)	46.0 ± 19.3
Children	13 (61.9)	7 (53.8)	6 (46.2)	36.6 ± 10.3
Siblings	5 (23.8)	4 (80)	1 (20)	33.6 ± 20.0
PSC probands	7	4 (57.1)	3 (42.9)	40.7 ± 9.5
PSC FDRs	19	9 (47.4)	10 (52.6)	49.9 ± 21.0
Parents	9 (47.4)	4 (44.4)	5 (55.6)	67.4 ± 9.4
Children	4 (21.1)	2 (50)	2 (50)	17.8 ± 2.2
Siblings	6 (31.6)	3 (50)	3 (50)	45.0 ± 6.1
Healthy controls	40	17 (42.5)	23 (57.5)	43.1 ± 9.8

Data are shown as n (%) or mean ± SD. PBC: Primary biliary cirrhosis; AIH-1: Autoimmune hepatitis-1; PSC: Primary sclerosing cholangitis; FDRs: First-degree relatives.

Table 2 Surgical history and comorbidities in first degree relatives of patients with autoimmune liver diseases and healthy controls n (%)

	PBC FDRs (n = 101)	AIH-1 and PSC FDRs (n = 40)	Healthy (n = 40)
History of comorbidities
Sjögren’s syndrome	7 (6.9)	1 (2.5)	0
Raynaud’s syndrome	8 (7.9)	2 (5)	0
Autoimmune thyroiditis	4 (3)	0	0
Rheumatoid arthritis	1 (1)	0	0
Systemic lupus erythematosous	0	1 (1)	0
Asthma	3 (3)	4 (10)	0
Atopic dermatitis	2 (2)	1 (2.5)	0
Vitiligo	1 (1)	0	0
Psoriasis vulgaris	1 (1)	0	0
Erythema nodosum	1 (1)	0	0
Type 1 diabetes mellitus	1 (1)	1 (2.5)	0
Idiopathic thrombocytopenic purpura	1 (1)	0	0
Osteoporosis	4 (4)	3 (7.5)	0
Urinary tract infections	33 (32.7)a	11 (27.5)	6 (15)
Hypercholesterolemia	10 (9.9)	7 (17.5)	4 (10)
Hypertension	6 (5.9)	5 (12.5)	3 (7.5)
History of surgery
Tonsillectomy	14 (13.9)	3 (7.5)	3 (7.5)
Appendectomy	18 (17.8)	7 (17.5)	5 (12.5)
Cholecystectomy	6 (5.9)	1 (2.5)	1 (2.5)
Inguinal hernia	14 (13.9)bc	0	1 (2.5)

^aP < 0.05 vs healthy controls;

^bP = 0.01 vs autoimmune hepatitis-1 (AIH-1)/primary sclerosing cholangitis (PSC) first-degree relatives (FDRs);

^cP = 0.05 vs healthy controls. PBC: Primary biliary cirrhosis.

Table 3 Autoantibody prevalence in first degree relatives of patients with primary biliary cirrhosis, compared to autoimmune hepatitis-1 and primary sclerosing cholangitis first degree relatives and healthy controls n (%)

Autoantibody	PBC FDRs (n = 101)	AIH-1 and PSC FDRs (n = 40)	Healthy controls (n = 40)	P1	P2
AMA (IIF)	10 (9.9)	1 (2.5)	0	NS	< 0.001
1:80	8 (7.9)	1 (2.5)	-
1:160	1 (1)	-	-
1:320	1 (1)	-	-
IgG MIT3-based ELISA	13 (12.9)	0	0	0.02	0.02
AMA positivity3	19 (18.8)	1 (2.5)	0	0.01	0.003
RL/M pattern	8 (7.9)	1 (2.5)	0	NS	NS
1:80	8 (7.9)	1 (2.5)	-
MND pattern	9 (8.9)	5 (12.5)	0	NS	0.06
1:80	7 (6.9)	3 (7.5)	-
1:160	1 (1.0)	-	-
1:320	-	2 (5.0)	-
1:640	1 (1.0)	-	-
PBC-specific ANA3 positivity	0	1 (2.5)	0	NS	NS

¹Comparison between primary biliary cirrhosis (PBC) first degree relatives (FDRs) and autoimmune hepatitis-1 or primary sclerosing cholangitis (AIH-1/PSC) FDRs; ²comparison between PBC FDRs and healthy controls;

³for definition of antimitochondrial antibodies (AMA) and PBC-specific antinuclear antibodies (ANA) positivity please see text (materials and methods section). IIF: Indirect immunofluorescence; ELISA: Enzyme-linked immunosorbent assay; RL/M: Rim-lime/membranous; MND: Multiple nuclear dot; NS: Not significant.

Table 4 Characteristics of first degree relatives according to antimitochondrial antibodies positivity

	AMA positive (n = 20)	AMA negative (n = 121)	P
Demographics
Female	12 (60)	63 (52.1)	NS
Age (yr)	47.8 ± 17.8	40.4 ± 18.0	NS
Proband disease (PBC)	19 (95)	87 (67.8)	0.012
Educational level, %			NS
Primary	41.70	26.50
Secondary	33.30	39.30
Higher	25	34.20
Body mass index (kg/m2)	25.7 ± 3.9	25.7 ± 5.0	NS
Smoking and alcohol consumption
Smoking	8 (40)	30 (27.5)	NS
Daily alcohol intake (g)	19.8 ± 38.2	17.7 ± 43.5	NS
Medical history
Urinary tract infection	11 (55)	33 (27.3)	0.01
Number of UTI events (range)	4 (1-5)	1 (1-2.5)	NS
Sicca symptoms	4 (20)	19 (15.7)	NS
Autoimmune disorders	3 (15)	5 (4.1)	NS
Autoimmune thyroid disease	2 (10)	2 (1.7)	NS
Diabetes	1 (5)	3 (2.5)	NS
Osteoporosis	0 (0)	7 (5.8)	NS
Tonsillectomy	4 (20)	13 (10.7)	NS
Appendectomy	3 (15)	22 (18.2)	NS
Inguinal hernia	2 (10)	12 (9.9)	NS
Laboratory values (U/L)
AST	29.6 ± 11.4	23.6 ± 9.7	NS
ALT	32.6 ± 25.5	26.1 ± 26.4	NS
γ-GT	29.6 ± 24.6	28.9 ± 37.7	NS
ALP	76.0 ± 23.3	73.5 ± 35.7	NS

Data are shown as n (%) or mean ± SD. UTI: Urinary tract infections; AMA: Antimitochondrial antibodies; PBC: Primary biliary cirrhosis; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; γ-GT: Gamma-glutamyl transpeptidase; ALP: Alkaline aminophosphatase; NS: Not significant.

Table 5 Characteristics of antimitochondrial antibodies-positive relatives with abnormal liver enzymes

	Age(yr)	Proband disease	Relationship to the proband	AST/ALT (U/L)	ALP/γ-GT (U/L)	Symptoms
Patient A	44	PBC	Son	37/45	102/122	No
Patient B	47	PBC	Brother	23/18	65/104	No
Patient C	40	PBC	Son	37/90	67/154	No
Patient D	24	PBC	Daughter	60/165	136/61	Sicca + Hashimoto’s thyroiditis
Patient E	52	PSC	Sister	53/103	91/94	Hashimoto’s thyroiditis

AST: Aspartate aminotransferase (upper limit: 35 U/L); ALT: Alanine aminotransferase (upper limit: 40 U/L); γ-GT: Gamma-glutamyl transpeptidase (upper limit: 37 U/L); ALP: Alkaline aminophosphatase (upper limit: 104 U/L); PBC: Primary biliary cirrhosis; PSC: Primary sclerosing cholangitis.