Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684275 (haemophilia)
 10,958 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite prophylactic treatment, haemophilia patients suffer from spontaneous joint bleeds, which lead to severe joint damage. Also after joint trauma, an intra-articular haemorrhage can add to joint damage over time. This study evaluated interleukin 10 (IL-10) in the search for possible interventions to prevent or limit the damaging effects of joint bleeds. Human articular cartilage tissue explants were cultured in the presence or absence of 50% v/v blood (or its cellular components) for 4 d (the expected blood load in vivo after a joint haemorrhage), followed by a recovery period of 12 d. Pharmacological dosages of IL-10 reached during treatment (1 or 10 ng/ml) were added. Additionally, cartilage and synovial tissue obtained from joints with end-stage haemophilic arthropathy (HA) were cultured in the presence of IL-10 (10 ng/ml). IL-10 protected cartilage from the damaging effects of blood exposure, measured by its effects on proteoglycan turnover. In addition, IL-10 beneficially influenced cartilage from patients with HA and reduced the production of the inflammatory cytokines IL-1beta and tumour necrosis factor-alpha by haemophilic synovial tissue. Taken together, although effects were obtained in vitro, IL-10 protects against blood-induced joint damage and might be further evaluated as candidate in treatment of tissue damaging effects of joint haemorrhages.
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PMID:Interleukin-10 protects against blood-induced joint damage. 1863 1

Antibodies that block factor VIII (FVIII) activity appear in some haemophilia A patients treated with FVIII replacement therapy and severely impaired treatment. To date, the mechanisms that lead to this immune response are unknown. In this work, haplotypes of cytokine interleukin 10 (IL-10) gene have been associated with the presence of FVIII inhibitors in a group of Brazilian haemophilia A patients. The coexistence of a haplotype defining high IL-10 synthesis and one defining an intermediate production of cytokines is found to be associated with the group of patients who have a history of inhibitor development. Additionally, the coexistence of haplotypes defining high and low IL-10 syntheses is strongly associated with the group of negative inhibitors. These results have shown that the simple association considering only the presence or the absence of a haplotype and the development of inhibitors in haemophilia A is not sufficient. Data obtained in this work sustain the idea that the genetic studies may partly explain why only approximately 25% of haemophilia A patients develop FVIII inhibitors. Other genetic issues and details of the protein replacement therapy should be considered to measure the chances of a patient to develop anti-FVIII antibodies.
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PMID:Analysis of cytokine genes polymorphism as markers for inhibitor development in haemophilia A. 2008 47

Current treatment of hemophilia consists of the administration of recombinant clotting factors, such as factor VIII (FVIII). However, patients with severe hemophilia can mount immune responses targeting therapeutically administered FVIII through inhibitory immunoglobulins that limit treatment efficacy. Induction of immune tolerance to FVIII in hemophilia has been extensively studied but remains an unmet need. We found that nondepleting anti-CD4 monoclonal antibodies (mAbs) are effective in inducing long-term tolerance to FVIII in different strains of hemophilic mice. Tolerance induction was facilitated when anti-CD4 mAbs were administered together with FVIII adsorbed in an adjuvant (alum). The observed state of tolerance was antigen specific, with mice remaining immune competent to respond to different antigens. Importantly, we found that following immunization with FVIII, the primed cells remained susceptible to tolerance induction. Studies with Foxp3-deficient and interleukin 10 (IL-10)-deficient mice demonstrated that the underlying tolerance mechanism is Foxp3 independent but requires IL-10. Our data show that an adjuvant, when administered together with a tolerizing agent such as nondepleting anti-CD4, can facilitate the induction of long-term tolerance to recombinant proteins, possibly not only in hemophilia but also in other diseases that are treated with potentially immunogenic therapeutics.
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PMID:Adjuvant facilitates tolerance induction to factor VIII in hemophilic mice through a Foxp3-independent mechanism that relies on IL-10. 2353 36