ESID Prague Spring Meeting 2009

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Presentation transcript:

ESID Prague Spring Meeting 2009 FUNCTIONAL INVESTIGATION OF ANTIBODY PRODUCTION IN COMMON VARIABLE IMMUNODEFICIENCY (CVID) PATIENTS UNDER IMMUNOGLOBULIN SUBSTITUTION Zita Trávníčková Department of Clinical Immunology and Allergology of St. Anne´s University Hospital and Medical Faculty of Masaryk University Brno ESID Prague Spring Meeting 2009

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

EXPERIMENTAL DESIGN SUBJECTS VACCINATION 37 CVID patients (15 males, 24 females, age range 20 - 74 years) 81 healthy donors (28 males, 53 females, age range 14 - 74 years) VACCINATION ALTEANA (Sevapharma a.s., Prague, Czech Republic) PNEUMO 23 (Sanofi Pasteur, Lyon, France) ELISPOT (isolated MNC of peripheral blood, calculated on CD19+) day 0, day 7, weeks 4-11

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)

FROM 4 TO 11 WEEKS AFTER VACCINATION HEALTHY DONORS BEFORE VACCINATION DAY 7 AFTER VACCINATION FROM 4 TO 11 WEEKS AFTER VACCINATION MED MIN MAX TAT SFC/106 BL IgG 10 367 330 86 747 IgA 482 24 8 876 IgM PCP 4 133 812 9 540 35 965 5 739 3 869 95 571 52 994 TAT + PCP 9 008 964 45 268 556 31 9 707 3 736 1 004 76 880 35 200 3 200 186 384 10 201 2 165 44 480

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

2% switched memory B cells 2% switched memory B cells EUROclass B-cells (Blood 2008) > 1% B cells  group B+ 1% B cells  group B- 2% switched memory B cells  group smB+ 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

EUROclass B cells CVID group B+ 37 patients group B- group smB+ group smB+21lo 10 patients group smB-21lo 12 patients group smB+21norm 6 patients group smB-21norm 9 patients

ELISPOT smB+21norm SmB+21lo CVID BEFORE VACCINATION PROTEIN antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6 7 8 9 10 smB+21norm PROTEIN Antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6

ELISPOT smB+21norm SmB+21lo CVID DAY 7 AFTER VACCINATION 713 2 562 659 PROTEIN antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6 7 713 8 9 2 562 659 10 104 smB+21norm PROTEIN Antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 185 4 231 5 407 6

ELISPOT smB+21norm SmB+21lo CVID 4-11 WEEKS AFTER VACCINATION PROTEIN antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6 7 8 9 10 smB+21norm PROTEIN Antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6

ELISPOT SmB-21lo smB-21norm CVID BEFORE VACCINATION PROTEIN Antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6 7 8 9 10 11 12 smB-21norm PROTEIN Antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6 7 8 9

ELISPOT smB-21norm SmB-21lo CVID DAY 7 AFTER VACCINATION 344 PROTEIN Antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6 7 8 344 9 10 11 12 smB-21norm PROTEIN Antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6 7 8 9

ELISPOT SmB-21lo smB-21norm CVID 4-11 WEEKS AFTER VACCINATION PROTEIN Antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6 7 8 9 10 11 12 smB-21norm PROTEIN Antigen SFC/106 B cells POLYSACCHARIDE IgG IgA IgM 1 2 3 4 5 6 7 8 9

CONCLUSIONS The ELISPOT assay is sensitive functional test for determination of specific antibody production in PID patients under substitution immunoglobulin therapy. In well-defined CVID patients almost no detectable peripheral B-cells producing specific IgG, IgA and IgM antibodies agains Tet. Tox. and PCP were observed. If the IgG response was detectable after Tet. Tox. vaccination most patients but not all were characterized as smB+21norm according to EUROclass.

2009 SPECIAL THANKS TO CO-WORKERS Department of Clinical Immunology and Allergology St. 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