Autoimmune Hepatitis

and, Diego Vergani; Mieli‐Vergani, Giorgina

doi:10.1002/9780470691861.ch11b

Cited by 23 publications

(20 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This observation, while not statistically significant, is intriguing since the HLA-A1, B8, DR3 haplotype has been associated with a variety of organ-specific autoimmune diseases, 20,21 such as in hypocomplementemia associated with systemic lupus erythematosis. 22,23 Historically, platelet transfusion refractoriness from HLA alloimmunization has been reported to respond poorly to therapeutic interventions, 7,9 as we also experienced.…”

Section: Discussionmentioning

confidence: 88%

Bleeding risk and platelet transfusion refractoriness in patients with acute myelogenous leukemia who undergo autologous stem cell transplantation

2000

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:Therapy for acute myelogenous leukemia can be complicated by alloimmunization to histocompatibility antigens (HLA), with resultant refractoriness to platelet transfusions. Autologous peripheral blood or bone marrow stem cell transplantation (referred here collectively as 'autoBMT') is emerging as a standard consolidative strategy in acute myelogenous leukemia (AML). We had noted life-threatening bleeding associated with platelet transfusion refractoriness following autoBMT; we therefore retrospectively analyzed 39 AML patients for this complication following BMT. All patients received high-dose chemoradiotherapy, followed by infusion of allogeneic sibling donor (n = 12, alloBMT) or autologous (n = 27, autoBMT) stem cells. HLA alloimmunization was assessed if patients were suspected of immune refractoriness to random donor platelet transfusions. Within 100 days of stem cell infusion, one of three alloBMT and six of 12 autoBMT recipients tested were HLA alloimmunized (not statistically significant, NS). Five of six HLA alloimmunized autoBMT patients experienced delayed bleeding, which contributed to their demise while still in remission (P Ͻ 0.001). Increased platelet requirements in HLA alloimmunized autoBMT recipients were observed between days 61 and 100 post-BMT, at a median of 211 platelet transfusions vs 0 in non-alloimmunized autoBMT patients (P Ͻ 0.01) and 17 in alloBMT patients. Our data suggest that platelet transfusion refractoriness, when associated with HLA alloimmunization, is a risk factor for increased platelet transfusion requirements, delayed bleeding, and poor outcome following autoBMT for AML. Bone Marrow Transplantation (2000) 26, 315-320.

show abstract

Section: Discussionmentioning

confidence: 88%

Bleeding risk and platelet transfusion refractoriness in patients with acute myelogenous leukemia who undergo autologous stem cell transplantation

2000

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…The deficiency of classical complement pathway factors has been most strongly related with systemic lupus erythematosus (20,21) and other immune complex-mediated diseases (22). C4 deficiency could thus be expected to increase EAMG incidence rather than decreasing it.…”

Section: Discussionmentioning

confidence: 99%

Genetic Evidence for Involvement of Classical Complement Pathway in Induction of Experimental Autoimmune Myasthenia Gravis

Tüzün

Scott

Goluszko

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Abs to acetylcholine receptor (AChR) and complement are the major constituents of pathogenic events causing neuromuscular junction destruction in both myasthenia gravis (MG) and experimental autoimmune MG (EAMG). To analyze the differential roles of the classical vs alternative complement pathways in EAMG induction, we immunized C3−/−, C4−/−, C3+/−, and C4+/− mice and their control littermates (C3+/+ and C4+/+ mice) with AChR in CFA. C3−/− and C4−/− mice were resistant to disease, whereas mice heterozygous for C3 or C4 displayed intermediate susceptibility. Although C3−/− and C4−/− mice had anti-AChR Abs in their sera, anti-AChR IgG production by C3−/− mice was significantly suppressed. Both C3−/− and C4−/− mice had reduced levels of B cells and increased expression of apoptotis inducers (Fas ligand, CD69) and apoptotic cells in lymph nodes. Immunofluorescence studies showed that the neuromuscular junction of C3−/− and C4−/− mice lacked C3 or membrane attack complex deposits, despite having IgG deposits, thus providing in vivo evidence for the incapacity of anti-AChR IgGs to induce full-blown EAMG without the aid of complements. The data provide the first direct genetic evidence for the classical complement pathway in the induction of EAMG induced by AChR immunization. Accordingly, severe MG and other Ab- and complement-mediated diseases could be effectively treated by inhibiting C4, thus leaving the alternative complement pathway intact.

show abstract

“…A Kindmark et al reported between the DRB1*07-DQA1*02 haplotype and autoimmune hepatitis type 2 12 and with drug-induced liver injury during antituberculosis treatment, 13 although the literature is inconsistent.…”

Section: Genome-wide Research Into Exanta Hepatic Adverse Eventsmentioning

confidence: 99%

Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis

et al. 2007

View full text Add to dashboard Cite

One of the major goals of pharmacogenetics is to elucidate mechanisms and identify patients at increased risk of adverse events (AEs). To date, however, there have been only a few successful examples of this type of approach. In this paper, we describe a retrospective case-control pharmacogenetic study of an AE of unknown mechanism, characterized by elevated levels of serum alanine aminotransferase (ALAT) during long-term treatment with the oral direct thrombin inhibitor ximelagatran. The study was based on 74 cases and 130 treated controls and included both a genome-wide tag single nucleotide polymorphism and large-scale candidate gene analysis. A strong genetic association between elevated ALAT and the MHC alleles DRB1*07 and DQA1*02 was discovered and replicated, suggesting a possible immune pathogenesis. Consistent with this hypothesis, immunological studies suggest that ximelagatran may have the ability to act as a contact sensitizer, and hence be able to stimulate an adaptive immune response.

show abstract

Autoimmune Hepatitis

Cited by 23 publications

References 51 publications

Bleeding risk and platelet transfusion refractoriness in patients with acute myelogenous leukemia who undergo autologous stem cell transplantation

Bleeding risk and platelet transfusion refractoriness in patients with acute myelogenous leukemia who undergo autologous stem cell transplantation

Genetic Evidence for Involvement of Classical Complement Pathway in Induction of Experimental Autoimmune Myasthenia Gravis

Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis

Contact Info

Product

Resources

About