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Diagnòstic de dèficit de producció danticossos específics. Eficàcia del tractament amb immunoglobulines en el control de lafectació pulmonar

by Vendrell Relat, Montserrat

Abstract (Summary)
Antibody response to an H.influenzae type b (Hib) conjugated vaccine was studied in 59 healthy adults (mean age: 32 yr) and 22 patients with knownhumoral immunodeficiencies (mean age: 32 yr) to determine its usefulness in the diagnosis of defective antibody formation. Twenty of the healthy adults and 9 of the patients were also immunized withPNU-Immune 23 a pneumococcal vaccine. Serum specific antibodies were measured by ELISAto Hib capsular polysaccharide. Adequate response to both vaccines was defined using the lower limit of the two-tailed 90% probability interval of postimmunization specific IgG of the healthy adults. By using this cutoff, responders were considered to be those with an absolute increase in anti-Hib IgG titers higher than 2.28 ?g/ml, and in anti-S.pneumoniae IgG higher than 395 arbitrary units/ml. With these criteria, 85% (50/59) of the healthy adults responded with anti-Hib IgG and 75% (15/20) with anti-pneumococcal IgG. All healthy adults receiving both vaccines responded to at least one. None of the patients with humoral immunodeficiencies responded to either vaccine. Evaluation of the antibody response to both the Hib and pneumococcal vaccines may facilitate the diagnosis of humoral immunodeficiency and selection of patients to receive immunoglobulin therapy. To ascertain whether antibody production deficiency with normal IgG levels is associated with bronchiectasis, antibody response to a pneumococcal unconjugate vaccine and an Hib conjugate vaccine was studied in all adult patients with bronchiectasis of unknown etiology that were assessed in our chest outpatient clinic from January 1994 to October 2001. Antibody production deficiency was defined as a failure to respond to either vaccine. 107 patients were included in the study (mean age: 46.3 years). Antibody production deficiency was diagnosed in 12 patients (11%). A significantly higher incidence of otitis media, lower serum IgG2 subclass levels, and lower preimmunization antibody levels to S.pneumoniae and Hib were observed in patients with antibody production deficiency. Antibody production deficiency with normal IgG levels may be associated with bronchiectasis, making it advisable to evaluate the antibody response to both the H.influenzae and pneumococcal vaccines in patients with bronchiectasis of unknown etiology, particularly in those with a history of otitis media, low IgG2 subclass levels and low levels of baseline specific antibodies. Lung damage progression is the most frequent condition in patients with common variable immunodeficiency (CVID). Appropriate immunoglobulin dose adjustments and follow-up guidelines to evaluate this have not been well established. To assess the evolution of lung damage once stable residual serum levels of IgG over 600 mg/dl had been achieved, a prospective study was conducted in 24 adult patients with CVID, with no previous intravenous immunoglobulin (IVIG) treatment. IVIG dose, total serum IgG level, bacterial infection rate, pulmonary function tests (PFTs) and high resolution computed tomography (HRCT) of the thorax were monitored over two years. IVIG dose variability (205 - 372 mg/kg/21 days) to obtain the required serum IgG levels was determined. Patients with chronic pulmonary disease (CPD) needed higher doses than those without CPD (p = 0.045). A significant reduction in severe and mild infections/patient-year was observed during treatment. Overall, there were no changes in PFTs and HRCT scores in patients without CPD, but both improved in patients with CPD. An increase of over 15% in overall HRCT score was detected in two patients without evidence of impairment in either clinical status or PFT values. Residual levels of total IgG over 600 mg/dl may help prevent progression of lung damage in patients with CVID. Levels of IgG, clinical manifestations and PFTs seem sufficient for routine follow-up. HRCT of the thorax, at least biennially, may help to identify patients in whom lung injury is progressing even though they may remain symptom-free and with stable PFTs.
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Bibliographical Information:

Advisor:Morell, Ferran; De Gracia, Javier

School:Universitat Autónoma de Barcelona

School Location:Spain

Source Type:Master's Thesis

Keywords:417 departament de medicina

ISBN:

Date of Publication:10/27/2004

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