Ignite Creation Date:
2024-05-06 @ 9:55 AM
Last Modification Date:
2024-10-26 @ 12:21 PM
Study NCT ID:
NCT03111589
Status:
COMPLETED
Last Update Posted:
2018-10-18
First Post:
2017-04-07
Brief Title:
Monocytic Expression of Heme Oxidase-1 HO-1 in Sickle Cell Patients and Correlation With the Humoral Immune Response to Vaccine and With Allo-immunization
Sponsor:
Francis Corazza
Organization:
Brugmann University Hospital
Study Overview
Official Title:
Monocytic Expression of Heme Oxidase-1 HO-1 in Sickle Cell Patients and Correlation With the Humoral Immune Response to Vaccine and With Allo-immunization
Status:
COMPLETED
Status Verified Date:
2018-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Sickle cell disease SCD is an autosomal recessive disorder resulting from a substitution in the β chain of hemoglobin Hb which causes hemoglobin S to polymerize when deoxygenated SCD patients present immune abnormalities that have always been attributed to functional asplenia It it is now being recognized that patients with SCD have a pro-inflammatory condition with altered immune system activation contributing to the pathology of SCD Increased levels of neutrophils monocytes or cytokines have been reported in SCD patients
SCD is associated with many acute and chronic complications requiring immediate support Actual strongly recommended therapies include chronic blood transfusions CT and hydroxyurea HU In addition episodic transfusions are recommended and commonly used to manage many acute SCD complicationsThere is strong evidence to support the use of HU in adults with 3 or more severe vaso-occlusive crises during any 12-month period with SCD pain or chronic anemia or with severe or recurrent episodes of acute chest syndrome HU use is now also common in children with SCD Some patients receive chronic monthly RBC transfusion with the objective to reduce the proportion of HbS to 30 Long-term RBC transfusions prevent and treat complications of SCD decreasing the risk of stroke and the incidence of acute chest syndrome ACS
Therapeutic complications such as alloimmunization against RBC in 20-50 of patients or hematopoietic stem cell transplantation HSCT graft rejection constitute an immune-based clinical issue in SCD Poorly understood RBC alloimmunization is responsible for serious hemolytic transfusion reaction associated with severe mortality and morbidity underlying the need for a better understanding of the immunology of SCD to improve SCD transfusion supportoutcome Little evidence exists about HU effects on immune functions in SCD HU treatment doesnt appear to have deleterious effects on immune function and appears to decrease the abnormally elevated number of total WBC and lymphocytes while CT does not
Patients with SCD are at higher risk of infections and prophylactic vaccination is strongly recommended Recent data suggest that vaccinal response to pneumococcal antigens in SCD patients is identical to healthy control while controversy concern the stability of the immune protection after vaccination of SCD patient Antibody levels declined over the year and the need for more frequent vaccination in SCD patient should be investigated Currently there is no evidence whether HU may interfere with pneumococcal immune response Purohit showed that immune response to inactivated influenza A H1N1 virus vaccine was altered in patient with SCD receiving CT but little is known on immune response to vaccination in patients with SCD receiving HU
Recent data suggest that not only inflammatory status but also humoral immune response to antigens in SCD patients may differ according to treatment Yazdanbakhsh reported an imbalance between regulatory T cell Treg and effector T cell Teff in alloimmunized SCD patients with as consequence an increase in antibody production In a model proposed by the authors the balance between Treg and Teff is dictated by the monocyte control of cytokines expression Altered activity of monocyte heme oxidase-1 HO-1 would be responsible of a decrease in IL-12 and an increase in IL-10 cytokines secretion impacting the TregTeff cells ratio and promoting antibody production by B cells
The objectives of the project are to assess whether different humoral immune responses to vaccines or to erythrocyte alloantigens are related to the type of treatment administered to patients with SCD We also aim to study if these differences might be related to different expressions of HO-1 by monocytes
SCD is associated with many acute and chronic complications requiring immediate support Actual strongly recommended therapies include chronic blood transfusions CT and hydroxyurea HU In addition episodic transfusions are recommended and commonly used to manage many acute SCD complicationsThere is strong evidence to support the use of HU in adults with 3 or more severe vaso-occlusive crises during any 12-month period with SCD pain or chronic anemia or with severe or recurrent episodes of acute chest syndrome HU use is now also common in children with SCD Some patients receive chronic monthly RBC transfusion with the objective to reduce the proportion of HbS to 30 Long-term RBC transfusions prevent and treat complications of SCD decreasing the risk of stroke and the incidence of acute chest syndrome ACS
Therapeutic complications such as alloimmunization against RBC in 20-50 of patients or hematopoietic stem cell transplantation HSCT graft rejection constitute an immune-based clinical issue in SCD Poorly understood RBC alloimmunization is responsible for serious hemolytic transfusion reaction associated with severe mortality and morbidity underlying the need for a better understanding of the immunology of SCD to improve SCD transfusion supportoutcome Little evidence exists about HU effects on immune functions in SCD HU treatment doesnt appear to have deleterious effects on immune function and appears to decrease the abnormally elevated number of total WBC and lymphocytes while CT does not
Patients with SCD are at higher risk of infections and prophylactic vaccination is strongly recommended Recent data suggest that vaccinal response to pneumococcal antigens in SCD patients is identical to healthy control while controversy concern the stability of the immune protection after vaccination of SCD patient Antibody levels declined over the year and the need for more frequent vaccination in SCD patient should be investigated Currently there is no evidence whether HU may interfere with pneumococcal immune response Purohit showed that immune response to inactivated influenza A H1N1 virus vaccine was altered in patient with SCD receiving CT but little is known on immune response to vaccination in patients with SCD receiving HU
Recent data suggest that not only inflammatory status but also humoral immune response to antigens in SCD patients may differ according to treatment Yazdanbakhsh reported an imbalance between regulatory T cell Treg and effector T cell Teff in alloimmunized SCD patients with as consequence an increase in antibody production In a model proposed by the authors the balance between Treg and Teff is dictated by the monocyte control of cytokines expression Altered activity of monocyte heme oxidase-1 HO-1 would be responsible of a decrease in IL-12 and an increase in IL-10 cytokines secretion impacting the TregTeff cells ratio and promoting antibody production by B cells
The objectives of the project are to assess whether different humoral immune responses to vaccines or to erythrocyte alloantigens are related to the type of treatment administered to patients with SCD We also aim to study if these differences might be related to different expressions of HO-1 by monocytes
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None