Association of primary biliary cirrhosis with the allele HLA-DPB1*0301 in a German population

Mella, Juan G.; Roschmann, Elke; Maier, K. P.; Volk, B

doi:10.1002/hep.1840210221

Cited by 36 publications

(27 citation statements)

References 46 publications

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“…HLA-DP associations have also been described in autoimmune diseases, such as CD (23), insulin-dependent diabetes mellitus (24), pauciarticular juvenile rheumatoid arthritis (25)(26)(27), and juvenile ankylosing spondylitis (28). In addition, an HLA-DP association has recently been demonstrated in primary biliary cirrhosis (29), in childhood common acute lymphoblastic leukemia (30), and also in Thai individuals with enhanced vaccine-induced Ab response to a malaria sporozoite Ag (31). However, some of these associations have not been confirmed (32,33), and in none of these examples has the association with HLA-DP been related to the restriction element used by T cells involved in the disease.…”

Section: Discussionmentioning

confidence: 99%

HLA-DP Allele-Specific T Cell Responses to Beryllium Account for DP-Associated Susceptibility to Chronic Beryllium Disease

Lombardi

Germain

Uren

et al. 2001

The Journal of Immunology

104

105

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Occupational exposure to small molecules, such as metals, is frequently associated with hypersensitivity reactions. Chronic beryllium (Be) disease (CBD) is a multisystem granulomatous disease that primarily affects the lung, and occurs in ∼3% of individuals exposed to this element. Immunogenetic studies have demonstrated a strong association between CBD and possession of alleles of HLA-DP containing glutamic acid (Glu) at position 69 in the HLA-DPβ-chain. T cell clones were raised from three patients with CBD in whom exposure occurred 10 and 30 years previously. Of 25 Be-specific clones that were obtained, all were restricted by HLA-DP alleles with Glu at DPβ69. Furthermore, the proliferative responses of the clones were absolutely dependent upon DPβ Glu69 in that a single amino acid substitution at this position abolished the response. As befits a disease whose pathogenesis involves a delayed type hypersensitivity response, the large majority of Be-specific clones secreted IFN-γ (Th1) and little or no IL-4 (Th2) cytokines. This study provides insights into the molecular basis of DP2-associated susceptibility to CBD.

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Section: Discussionmentioning

confidence: 99%

HLA-DP Allele-Specific T Cell Responses to Beryllium Account for DP-Associated Susceptibility to Chronic Beryllium Disease

Lombardi

Germain

Uren

et al. 2001

The Journal of Immunology

104

105

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“…36 It is possible that positive association might be 41 This association was not confirmed in several other studies from different non-British European populations. 32,35,36,42,43 Moreover, other European studies suggested significant associations of PBC with DR3 29,35 and DPB1*0301, 44 while the most recent study from the United States demonstrated an association between DRB1*08-DQA1*0401-DQB1*04 haplotype and PBC, albeit in a minority of patients. 40 Finally, studies from Japan failed to provide a consistent picture of HLA class II associations with PBC.…”

Section: Mhc and Pbcmentioning

confidence: 96%

Genes and (auto)immunity in primary biliary cirrhosis

et al. 2005

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Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease most commonly encountered in postmenopausal women; it is characterized by high-titer serum autoantibodies to mitochondrial antigens, elevated serum IgM, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. The cytopathic mechanisms leading to the selective destruction of intrahepatic cholangiocytes are still largely unknown. The current theory on the pathogenesis of PBC indicated that environmental factors might trigger autoimmunity in genetically susceptible individuals. In fact, genetic predisposition is critical to disease onset and progression, yet peculiar among autoimmune diseases, as indicated by the lack of a strong association with major histocompatibility complex haplotypes. Further, the recently reported concordance rate among monozygotic twins strenghtens the importance of genetic factors, while also indicating that additional factors, possibly infectious agents or xenobiotics, intervene to trigger the disease. In this review, the available data regarding the genetic factors associated with PBC susceptibility and progression, as well as the available evidence regarding the immunomediated pathogenesis of PBC, will be critically illustrated and discussed.

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“…However, it is to note that several European studies have failed to confirm an association with DRB1*08 (31, 52, 55, 57, 63). Other than DRB1*08 variant, it has been reported associations with DR3 (49, 55) or DPB1*0301 (64). In 2003, we suggested that the DRB1*11 allele has a protective effect against PBC in the Italian population (57).…”

Section: Hla Associations and Pbcmentioning

confidence: 99%

Human leukocyte antigen in primary biliary cirrhosis: An old story now reviving

Invernizzi

2011

Hepatology

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Primary biliary cirrhosis (PBC) is an autoimmune biliary disease characterized by injury of small and medium size bile ducts eventually leading to liver cirrhosis and death. While the causes remain enigmatic, recent evidence has strengthened the importance of genetic factors in determining the susceptibility to the disease. Besides the strong heritability suggested by familial occurrence and monozygotic twins concordance, for decades there has not been a clear association with specific genes, with the only exception of a low risk conferred by a class II human leukocyte antigen (HLA) variant, the DRB1*08 allele, at least in some populations. Only recently the story began to change when a strong protective associations between PBC and the HLA DRB1*11 and DRB1*13 alleles were found in Italian and UK series. But HLA genes fully returned to attract interest thanks to recent genome-wide association studies (GWAS) which clearly demonstrated that the major component of the genetic architecture of PBC are within the HLA region. As expected in a genetically complex disease, GWAS also identified several novel non-HLA variants, but it is to note that all of them are in immuno-related genes. In this review, the paradigmatic tale of what, and how, we learned about HLA genes in PBC will be retraced with particular focus on how GWAS are enabling us to rewrite the story of PBC pathogenesis. These recent discoveries will not only driving functional studies but will also held the promise of developing novel disease-specific treatments.

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Association of primary biliary cirrhosis with the allele HLA-DPB1*0301 in a German population

Cited by 36 publications

References 46 publications

HLA-DP Allele-Specific T Cell Responses to Beryllium Account for DP-Associated Susceptibility to Chronic Beryllium Disease

HLA-DP Allele-Specific T Cell Responses to Beryllium Account for DP-Associated Susceptibility to Chronic Beryllium Disease

Genes and (auto)immunity in primary biliary cirrhosis

Human leukocyte antigen in primary biliary cirrhosis: An old story now reviving

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