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Functional Investigation of Antibody Production in CVID Patients Under Ig Substitution Therapy

This study explores specific antibody production in patients with Common Variable Immunodeficiency (CVID) undergoing immunoglobulin substitution therapy. We utilized the ELISPOT assay to assess B-cell functionality in 37 CVID patients and 81 healthy donors post-vaccination. Our findings indicate a notable lack of detectable peripheral B-cells producing IgG, IgA, and IgM antibodies against various antigens in CVID patients. The ELISPOT assay proved sensitive for evaluating specific antibody production in patients with primary immunodeficiencies, emphasizing the challenges in immune response assessment in CVID.

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Functional Investigation of Antibody Production in CVID Patients Under Ig Substitution Therapy

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  1. FUNCTIONAL INVESTIGATION OF ANTIBODY PRODUCTION IN COMMON VARIABLE IMMUNODEFICIENCY (CVID) PATIENTS UNDER IMMUNOGLOBULIN SUBSTITUTION Zita Trávníčková Department ofClinicalImmunologyandAllergologyof St. Anne´s University HospitalandMedicalFacultyof Masaryk University Brno ESID PragueSpring Meeting 2009

  2. ELISPOT assay in PID functional investigation of B cells Detection of specific antibody production on B cell level independent on substitution Ig therapy

  3. EXPERIMENTAL DESIGN SUBJECTS • 37 CVID patients (15 males, 24 females, agerange20 - 74 years) • 81 healthydonors (28 males, 53 females, agerange 14-74 years) VACCINATION • ALTEANA (Sevapharmaa.s., Prague, Czech Republic) • PNEUMO 23 (Sanofi Pasteur, Lyon, France) ELISPOT(isolated MNC ofperipheralblood, calculated on CD19+) • day 0, day 7, weeks 4-11

  4. HEALTHY DONORS Vaccination with PROTEIN antigen 50 controls (16 males, 34 females, age range 22 – 72 years) Vaccination with POLYSACHARIDE antigen 10 controls ( 4 males, 6 females, age range 15 – 46 years) Vaccination with PROTEIN and POLYSACHARIDE antigen 21 controls (8 males, 13 females, age range 14 – 50 years)

  5. CVID PATIENTS Vaccination with PROTEIN and POLYSACHARIDE antigen 37 patients (15 males, 24 females, age range 20 - 74 years)

  6. EUROclassB-cells (Blood 2008) > 1% B cells  group B+ • 1% B cells •  group B- • 2% switchedmemory B cells •  groupsmB+ • 2% switched memory B cells •  group smB-  10% CD 21low B cells group smB-21lo  10% CD 21low B cells group smB+21lo < 10% CD 21low B cells group smB+21norm < 10% CD 21low B cells group smB-21norm

  7. CVID EUROclassB cells group B+ 37 patients group B- group smB+ 16 patients group smB- 21 patients group smB+21lo 10 patients group smB-21lo 12 patients group smB+21norm 6 patients group smB-21norm 9 patients

  8. ELISPOT CVID BEFORE VACCINATION

  9. ELISPOT CVID DAY 7 AFTER VACCINATION

  10. ELISPOT CVID 4-11 WEEKS AFTER VACCINATION

  11. ELISPOT CVID BEFORE VACCINATION

  12. ELISPOT CVID DAY 7 AFTER VACCINATION

  13. CVID 4-11 WEEKS AFTER VACCINATION ELISPOT

  14. CONCLUSIONS The ELISPOT assayissensitive functional test fordeterminationofspecificantibodyproduction in PIDpatientsundersubstitutionimmunoglobulintherapy. In well-defined CVID patientsalmost no detectableperipheral B-cellsproducingspecific IgG, IgA and IgM antibodiesagains Tet. Tox. and PCP wereobserved. Ifthe IgG response wasdetectableafter Tet. Tox. vaccination most patientsbut not allwerecharacterized as smB+21norm according to EUROclass.

  15. 2009 SPECIAL THANKS TO CO-WORKERSDepartment of Clinical Immunology and AllergologySt. Anne´s University hospital and Medical Faculty of Masaryk University in Brno prof. MUDr. Jiří Litzman, CSc. MUDr. Vojtěch Thon, Ph.D. Mgr. Marcela Vlková, Ph.D. 1910 St. Anne´s University Hospital Brno

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