Autoantibodies in primary sclerosing cholangitis

Table 1 Autoantibodies detected in PSC patients

Antibody	Prevalence (%)	(Median)	No. of patients	(Median)	No. of articles
Anti-BEC	63	(63)	30	(30)	1[36]
pANCA	26-94	(68)	13-86	(30)	19 (Table 2)
AMA	0-9	(0)	15-73	(37)	10[44617889102112137–140]
Anti-LKM	0	(0)	10-80	(37)	7[4489112137140–142]
Anti-SLA/LP	0	(0)	10-37	(25)	4[4489140142]
ANA1	8-77	(30)	13-73	(35)	13[4461788999101102111112137–140]
SMA1	0-83	(17)	10-73	(36)	10[44617889111112137–140]
ASCA	44	(44)	25	(25)	1[115]
Anti-cardiolipin	4-63	(27)	23-73	(41)	3[617887]
Rheumatoid factor	15	(15)	71	(71)	1[78]
AECA	35	(35)	20	(20)	1[87]
Anti-TPO	16	(16)	73	(73)	1[78]
Anti-GBM	17	(17)	24	(24)	1[87]
Anti-sulfite oxidase	33	(33)	39	(39)	1[130]
Anti-GSTT1	5	(5)	58	(58)	1[133]

PSC: Primary sclerosing cholangitis; Anti-BEC: Antibodies against biliary epithelial cells (measured with flow cytometry); PANCA: Perinuclear antineutrophil cytoplasmic antibodies; ANA: Antinuclear antibodies; SMA: Smooth muscle antibodies; ASCA: Anti saccharomyces cerevisiae antibodies; AMA: Anti-mitochondrial antibodies; Anti-LKM: Liver-kidney microsomal antibodies; Anti-SLA/LP: Antibodies against soluble liver antigen/liver pancreas; AECA: Anti-endothelial cell antibodies; Anti-TPO: Antibodies against thyroid peroxidase; Anti-GBM: Antibodies against the glomerular basement membrane; Anti-GSTT1: Antibodies against glutathione S transferase theta 1.

¹In the largest cohort investigated, ANAs and/or SMAs were detected in 22% (24/111) of the PSC patients, but the frequency of each type was not given[143].

Table 2 Prevalence of pANCA¹ in PSC patients and controls² [% (n^{antibody positive}/n^{total population})]

Authors	PSC	PSC -IBD	PSC+IBD	UC -PSC	CD-PSC	AIH	PBC	HC	MT
Terjung et al[44]	943					814 (142/175)	31	0	IIF
	(33/35)						(14/45)	(0/19)	1:10
Klein et al[54]	87			78	27			0	IIF
	(26/30)			(18/23)	(16/60)			(0/20)	1:10
Mulder et al[102]	79	775	825			886	28	5	IIF
	(19/24)	(10/13)	(9/11)			(21/24)	(7/25)	(12/252)	1:32
Lo et al[56]	777			33	0	336	0	0	AP
	(23/30)			(15/45)	(0/32)	(1/33)	(0/14)	(0/50)	1:10
Seibold et al[98]	775	408	88	83	25	336	28	0	IIF
	(17/22)	(2/5)	(15/17)	(38/46)	(20/80)	(5/15)	(7/28)	(0/30)	1:10
Gur et al[87]	75	75	755						IIF
	(15/20)	(3/4)	(12/16)						1:20
Muratori et al[144]	75					314	2	0	IIF
	(18/24)					(12/39)	(1/51)	(0/18)	1:20
Seibold et al[84]	72	50	765	62	4	354	28	0	IIF
	(18/25)	(2/4)	(16/21)	(30/48)	(2/48)	(8/23)	(6/21)	(0/40)	1:10
Zauli et al[137]	72								IIF
	(33/46)								-9
Hardarson et al [145]	69	75	675	76	8	506	0		IIF
	(20/29)	(6/8)	(14/21)	(16/21)	(2/25)	(10/20)	(0/33)		1:40
Roozendaal et al[99]	67								IIF
	(46/69)								1:40
Bansi et al[146]	6610					656	13	0	AP
	(57/86)					(11/17)	(7/55)	(0/36)	1:5
	5110					656	11	0	IIF
	(44/86)					(11/17)	(6/55)	(0/36)	1:5
Bansi et al[101]	65	29	705	45				0	AP
	(41/63)	(2/7)	(39/56)	(38/85)				(0/36)	1:05
Tervaert et al[88]	62					716	33	0	IIF
	(8/13)					(5/7)	(5/15)	(0/24)	-9
Roozendal et al[57]	49					7011	15	0	IIF
	(27/55)					(62/88)	(8/53)	(0/78)	1:40
Claise et al[53]	44	25	60	37	15	2411	0	0	IIF
	(12/27)	(3/12)	(9/15)	(18/49)	(11/75)	( 25/105)	(0/30)	(0/50)	1:20
Vermeulen et al[147]	44			56	15	466		5	IIF
	(16/36)			(56/100)	(15/100)	(17/37)		(5/105)	1:40
Wilschanski et al[60]	29								IIF
	(7/24)								1:20
Pokorny et al[100]	26	29	23			226	0		IIF
	(10/39)	(5/17)	(5/22)			(2/9)	(0/7)		1:20

PSC: Primary sclerosing cholangitis; IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s disease; AIH: Autoimmune hepatitis; PBC: Primary biliary cirrhosis; HC: Healthy controls; MT: Method and titre considered positive (cut-off); IIF: Indirect immunofluorescence; AP: Alkaline phosphatase method.

¹No distinction between classical/atypical;

²The single largest study of autoantibodies in PSC reported ANCAs among 84% (61/73) of the patients, but this study did not apply IIF, meaning that this figure is the total of patients with any ANCA subspecificity[78];

³Atypical pANCA (as opposed to classical pANCA or cANCA);

⁴autoimmune hepatitis type 1 and 2;

⁵Calculated from article values;

⁶Autoimmune hepatitis not subclassified (1 or 2);

⁷ANCA "type 1 pattern" is interpreted as pANCA, including both IgA/IgM/IgG;

⁸Significant difference between PSC +IBD and PSC -IBD (P value not given);

⁹Details not given, correspondence, not peer-reviewed;

¹⁰Calculated sum of 4 patient populations from different countries;

¹¹Autoimmune hepatitis type 1.

Table 3 Prevalence of antibodies against a selection of specific neutrophil antigens in PSC patients

Antibody	Frequency range % (median)	No. of patients range (median)	Number of studies
Anti-lactoferrin	4-50 (29)	12-76 (24)	10[55578485878899102137144]
Anti-myeloperoxidase	0-33 (2)	12-73 (40)	7[577884858799102]
Anti-BPI	5-46 (29)	36-76 (69)	5[5557597899]
Anti-cathepsin G	0-35 (21)	14-76 (55)	5[5557848799]
Anti-proteinase 3	0-44 (4)	25-73 (62)	5[57788799102]
Anti-elastase	0-35 (9)	23-76 (69)	4[558799102]
Anti-α-enolase	11-33 (27)	15-55 (36)	3[5789147]
Anti-catalase	16-60 (38)	15-55 (35)	2[5789]
Anti-α-antigen	33 (33)	12 (12)	1[85]
Anti-h-lamp-2	71 (71)	73 (73)	1[78]
Anti-TBB51

PSC: Primary sclerosing cholangitis; Anti-BPI: Antibodies against bactericidal/permeability increasing protein; Anti-h-lamp-2: Antibodies against human lysosomal-associated membrane protein 2; Anti-TBB5: Antibodies against Tubulin beta-5 chain.

¹No prevalence studies published.