Role for mycobacterial infection in pathogenesis of primary biliary cirrhosis?

Table 1 Prevalence of granulomas in liver disease n (%)

Ref.	Origin	Total number liver biopsies	Total number liver biopsies with granulomas	Diagnosis of PBC in granuloma group
Drebber et al[100]	Germany	12  161	442 (3.6)	215 (48.6)
Dourakis et al[101]	Greece	1768	66 (3.7)	41 (62)
Gaya et al[95]	United Kingdom	1662	63 (3.8)	15 (23.8)
McCluggage et al[96]	Northern Ireland	4075	163 (4)	90 (55)
Satti et al[99]	Saudi Arabia	404	59 (14.6)	Unknown

PBC: Primary biliary cirrhosis.

Table 2 Summary of studies in support or against a role of mycobacteria as triggers of primary biliary cirrhosis

Ref.	Year	Mycobacterium	M2 antigen	In support	Against
Klein et al[88]	1993	M. tuberculosis	Bovine heart	Anti-M2 AMAs (70 kDa) found in 12/28 (43%) tuberculosis patients	None of the patients had PBC
					AMA by IIFL were negative
					Anti-PDC-E2 titers were low
Gilburd et al[87]	1994	M. leprae	Bovine heart	Anti-M2 against 54-, 41- and 35-kDa bands found in 27/69 (39.1%) leprosy patients	None of the patients had PBC
					Only 2/27 (1%) sera reacted with the PDC-E2 band
					Anti-M2 inhibited anti-PDC activity in 19.1%
Vilagut et al[86]	1994	M. gordonae	Porcine heart	Anti-hsp65 M. gordonae antibodies found in 19/19 (100%) of PBC patients. No reactivity to other atypical mycobacteria was found
				Anti-porcine AMAs (anti-PDC-E2 and BCOADC-E2) cross-reacted with anti-hsp65 M. gordonae antibodies and vice versa
O’ Donohue et al[119]	1994	M. gordonae, M. kansasii, M. fortuitum, M. chelonae, M. szulgai and M. malmoense, M. avium-intracellulare and M. xenopi		23 of 26 (88%) PBC sera reacted with a 65-kDa protein in extracts of six of the mycobacterial species tested	Reactivity to the atypical mycobacterial mimics was found in non-PBC liver disease patients and controls
				Sera from 15 PBC patients reacted with M. avium-intracellulare
				Sera from 9 PBC patients reacted with M. xenopi
Bogdanos et al[54]	2004	M. gordonae	Primate liver	The motif GDL(IL)AE is shared by M. gordonae hsp6594-99 and PDC-E2216–221	Reactivity to M. gordonae hsp6590-104 /human PDC-E2212-226 seen in Spanish (47.5%), but rarely British patients (4%)
Broome et al[121]	1993	-	-	Immunohistochemistry demonstrated positive mycobacterial hsp65 staining in PBC liver tissue	Positive staining was also observed in pathological controls
Vilagut et al[116]	1996	M. gordonae	-	M. gordonae genetic material detected in 9 of 11 (82%) PBC liver tissues
O’Donohue et al[118]	1998	M. gordonae	-		Mycobacterial DNA not detected in PBC liver tissues, but was detected in positive controls
Tanaka et al[122]	1999	Mycobacterial genus specific primers	-		Mycobacterial DNA not detected in PBC liver tissues

M. tuberculosis: Mycobacterium tuberculosis; M. leprae: Mycobacterium leprae; M. gordonae: Mycobacterium gordonae; M. kansasii: Mycobacterium kansasii; M. fortuitum: Mycobacterium fortuitum; M. chelonae: Mycobacterium chelonae; M. szulgai: Mycobacterium szulgai; M. malmoense: Mycobacterium malmoense; M. avium-intracellulare: Mycobacterium avium-intracellulare; M. xenopi: Mycobacterium xenopi; IIFL: Indirect immunofluorescence; PDC: Pyruvate dehydrogenase complex; PBC: Primary biliary cirrhosis; AMAs: Antimitochondrial antibodies; hsp: Heat shock protein.