The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood

Table 1

Publications on major histocompatibility class II human leukocyte antigens and their association with primary sclerosing cholangitis patients.

Reference	Total number of patients/controls (number of children and adolescents)	What was evaluated	Conclusions
Farrant et al. [32], 1992	71/68 (0)	HLADRB, DQA, and DQB	HLADRB30101 was the most associated allele, with reduced survival of patients with it. DRB50101 was another susceptibility allele and DRB40101 demonstrated a likely protective function.
Amar et al. [33], 1992	15/no control (0)	HLADRB3	No apparent association of the alleles of the DRB3 locus in the Israeli population.
Olerup et al. [34], 1995	75/250 (not cited)	HLADR and DQ	Association with DRB11301, DQAI0103, and DQBI0603 haplotype was confirmed, whereas DRB104 was only slightly underrepresented.; No difference was observed in age, presentation, liver function, histological stage, or survival between patients with different positive alleles.
Leidenius et al. [35], 1995	24/106 (not cited)	HLA-A, B, C and DR	HLA-B8 and DR3 (DRB103) were associated with primary sclerosing cholangitis.
Wilschanski et al. [36], 1995	27/no control (all children)	HLA-B and HLADR	An increased incidence of HLA B8 and DR2 (DRB115) but not DRw52a (DRB30101) was found.
Spurkland et al. [30], 1999	256/764 (not cited)	HLADR and DQ	Increased frequencies of DRB103-DQA10501-DQB102, DRB113-DQA10103-DQB10603, and DRB115-DQA10102-DQB10602 haplotypes were observed.; PSC was negatively associated with DRB104-DQB10302 haplotype.
Boberg et al. [37], 2001	265/no control (yes, but the number was not cited)	HLADR and DQ	DRB103-DQA10501-DQB102 (i.e., DR3, DQ2) heterozygous genotype was associated with an increased risk of death or liver transplantation.; Presence of a DQ6 encoding haplotype (DQB10603 or DQB10602) in DR3, DQ2 negative individuals was associated with a reduced risk of death or liver transplantation.
Donaldson and Norris [31], 2002	148/134 (0)	HLADR and DQ	Associations with the DRB30101-DRB10301-DQA10501-DQB10201 and DRB11301-DQA10103-DQB10603 haplotypes were confirmed.; Protective influence of the DRB104-DQB10302 haplotype was reaffirmed.; A previously unreported protective haplotype was found: DRB10701-DQB10303.
Bittencourt et al. [38], 2002	63/83 (27)	HLA-B, DRB1, DQB1	No increase in the frequency of HLA-B, DRB3, DRB4, or DRB5 alleles was observed.; The frequency of HLA-DRB11301 and HLA-DQB106 was significantly increased in PSC patients.
Neri et al. [39], 2003	64/183 (0)	HLA-DRB1, HLA-DQB1, and HLA-B	Frequencies of DRB101-DQA10101-DQB10102, DRB116-DQA10102-DQB10502, and DRB104-DQA103-DQB10301 haplotypes were more elevated in PSC patients.; DRB107-DQA10201-DQB102 haplotype frequency was significantly decreased in patients.
Karlsen et al. [25], 2010	285/298 (yes, but the number was not cited)	HLADR and DQ	The strongest association was detected for HLA-B08 and associations with the DRB1 alleles -DRB103, -DRB104, -DRB107, and -DRB11301 also were confirmed.
Hov et al. [40], 2010	78/79 (not cited)	HLADRB1, HLA-C	Positive association of PSC with HLADRB115,; -DRB103, -DRB104, and; -DRB11301 was confirmed.; A protective association with HLADRB10701 was found.
Wang et al. [41], 2014	31/42 (all children)	HLADR haplotypes	Frequencies of homozygous HLA DRB10301 (DR3) genes and haplotype A1-B8-DR3 were higher in patients.; Frequencies of disease-protective genes DR4 and/or DR15 were lower in the patients.
Næss et al. [42], 2014	365/368 (yes, but the number was not cited)		HLADRB11301-DQB10603 and DRB11501 haplotypes conferred risk for PSC.; HLADRB104-DQB103, DRB10701-DQ0303, and DR13:XX (all non-13:01 alleles)-DQB106 demonstrated a protective effect.

HLA: human leukocyte antigen; MHC: major histocompatibility complex; PSC: primary sclerosing cholangitis.