Impaired Antibody Responses Research Articles

Decreased CD27+ Memory B cells in DiGeorge Anomaly

ABSTRACT Patients with DiGeorge anomaly (DGA) have a variety of B-cell immune deficiencies, including IgA deficiency and impaired polysaccharide antibody responses. CD27+ memory B cells have been found to be decreased in a variety of B-cell immunodeficiencies, such as selective antibody deficiency (SAD). We evaluated for a correlation between reduced CD27+ memory B cells and impaired polysaccharide antibody responses in patients with DGA. A retrospective analysis of DGA patients referred for recurrent sinopulmonary infections was performed. Twenty-one patients with DGA (62% male and median age was 5 ± 0.8 years) were evaluated. Six patients had reduced CD3+ T cells, and two patients had reduced CD4+ T cells, but none had opportunistic infections. B-cell numbers and percentages were normal in all patients, but the percentages of memory CD27+ B cells were decreased compared to normal values, 12 ± 2% versus 34%. CD27+ B cells were <15% in 86% of patients. Eighty-one percent of patients had reduced protective...

Smoking impairs human papillomavirus (HPV) type 16 and 18 capsids antibody response following natural HPV infection

The natural history of oncogenic human papillomavirus (HPV) infections results from interactions of the virus, the host, and multiple cofactors. We studied the association between humoral immune response to HPV and smoking in 191 HPV infected women prospectively. Two follow-up samples (first and last) were analysed for serum cotinine levels, IgA and IgG antibodies to HPV16 and 18, and Chlamydia trachomatis using ELISA methods. HPV DNA analyses were also performed, and HPV16/18 antibodies were detectable in 23 of 40 (57.5%) HPV DNA-positive women. We performed age-stratified analyses and found that young smokers were less likely to develop HPV16/18 antibodies than non-smokers (OR: 0.2, 95% CI 0.0-0.9). Furthermore, they had a significantly decreased tendency of maintaining constant HPV16/18 IgG antibody positivity by the end of the follow-up (OR: 0.1, 95% CI 0.0-0.8). Smoking did not affect the development of HPV antibody responses in women over 30 y of age. Our results suggest that smoking may induce impaired antibody response in HPV16/18-infected young women.

Circulating memory B-cell subpopulations are affected differently by HIV infection and antiretroviral therapy

To determine if the depletion of IgM memory B cells might contribute to the increased susceptibility of HIV patients to pneumococcal infection, memory B-cell subpopulations were investigated in HIV patients, including patients receiving antiretroviral therapy (ART). Blood B cells with the phenotype of IgM memory B cells (CD27, IgM) and switched memory B cells (CD27, IgM) were measured in antiretroviral-treated (n = 32) and untreated (n = 24) HIV patients and non-HIV controls (n = 35). Serum levels of IgG and IgG2 antibodies to pneumococcal polysaccharides, IgG, IgG subclasses, IgM and IgA were also assayed in HIV patients. Switched memory B-cell counts were lower than controls in HIV patients (P < 0.01) irrespective of antiretroviral status and correlated with CD4 T-cell counts (r = 0.56, P = 0.001) in treated patients. In untreated patients, IgM memory B-cell counts correlated with CD4 T-cell counts (r = 0.73, P < 0.0001) reflecting higher values than controls in patients with CD4 T-cell counts greater than 300 cells/microl (P = 0.004) and lower values than controls in patients with CD4 T-cell counts below 300 cells/microl (P = 0.0001). There was no relationship between serum levels of pneumococcal antibodies and IgM or switched memory B cells. The depletion of IgM memory B cells in untreated HIV patients with a CD4 T-cell count below 300 cells/microl might be a risk factor for pneumococcal infection. The depletion of switched memory B cells is a complication of HIV infection irrespective of ART and might contribute to impaired IgG antibody responses. Memory B-cell subpopulations might predict the risk of pneumococcal sepsis more accurately than the CD4 T-cell count or pneumococcal antibody levels.

Transmembrane activator and calcium modulator and cyclophilin ligand interactor enhances CD40-driven plasma cell differentiation

Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a receptor used by B cell-activating factor of the TNF family and a proliferation-inducing ligand (APRIL) to induce isotype switching independently of CD40 and is mutated in patients with common variable immunodeficiency. We sought to determine whether TACI and CD40 cooperate in inducing class switch recombination and immunoglobulin production. Naive mouse B cells were stimulated with suboptimal concentrations of anti-CD40 plus IL-4 in the presence or absence of APRIL or anti-TACI. IgG(1) and IgE production was measured by means of ELISA. mRNA for Cgamma(1) and Cepsilon germ-line transcripts, activation-induced cytidine deaminase, and mature gamma(1) and epsilon transcripts were measured by means of RT-PCR. Plasmablasts were enumerated by using syndecan-1/CD138 staining. Interferon regulatory factor 4, B lymphocyte-induced maturation protein 1, and IL6 mRNA expression was measured by using quantitative PCR. TACI ligation enhanced IgG(1) and IgE secretion by naive murine B cells stimulated by anti-CD40 plus IL-4, with little effect on B-cell proliferation or class switch recombination. In contrast, TACI ligation of anti-CD40 plus IL-4-stimulated B cells induced a significant increase in syndecans-1/CD138-positive cells. TACI ligation caused a modest but significant increase in the expression of interferon regulatory factor 4, with no detectable change in B lymphocyte-induced maturation protein 1 expression. TACI and CD40 signaling converge to promote B-cell differentiation into plasmablasts. Our data suggest that TACI dysfunction could contribute to the impaired antibody response to T-dependent antigens in common variable immunodeficiency.

B Cell-Specific Deletion of Protein-Tyrosine Phosphatase Shp1 Promotes B-1a Cell Development and Causes Systemic Autoimmunity

Spontaneous loss-of-function mutations in the protein-tyrosine phosphatase Shp1 cause the motheaten phenotype, characterized by widespread inflammation and autoimmunity. Because Shp1 is expressed in all hematopoietic cells, it has been unclear which aspects of the motheaten phenotypes are primary effects of Shp1 deficiency. We generated mice (Ptpn6(f/f);CD19-cre) that delete Shp1 specifically in B cells. Analysis of these mice indicates that the increase in B-1a cells in motheaten mice is a cell-autonomous consequence of Shp1 deficiency. Shp1-deficient B-1a cells could be derived from adult bone marrow and had N-nucleotide additions, consistent with an adult origin. Shp1 deficiency altered calcium response evoked by B cell antigen receptors and impaired CD40-evoked proliferation. Young Ptpn6(f/f);CD19-cre mice exhibited elevated serum immunoglobulins and impaired antibody responses to immunization, whereas older Ptpn6(f/f);CD19-cre mice developed systemic autoimmunity, characterized by DNA antibodies and immune complex glomerulonephritis. Thus, Shp1 deficiency in B cells alone perturbs B cell development and causes autoimmune disease.

Impaired responses to pneumococcal polysaccharide in CD21/35-deficient mice are caused by dysregulated CD19 expression (53.14)

Abstract Humoral responses to T cell-independent type 2 (TI-2) antigens, such as pneumococcal polysaccharide (PPS), are critical for providing rapid protection during infections. Complement receptor 1/2 (CD21/35) expression is required for optimal antibody responses, as CD21/35-deficient (CD21/35−/−) mice mount impaired humoral immune responses to TI-2 antigens. CD21/35 associates with CD19, a potent regulator of B cell Src family kinase activity. Altered CD19 expression has dramatic effects on B cell subset development and functional activity. Importantly, CD21/35 deficiency results in significantly increased CD19 expression. To determine whether altered CD19 expression levels in CD21/35−/− mice affect TI-2 responses, CD21/35−/− mice deficient in CD19 were generated and analyzed for their responsiveness to TI-2 antigens, including type 3 PPS and haptenated-Ficoll. CD21/35−/− mice generated impaired TI-2 antibody responses to each antigen, whereas CD19−/− mice generated normal or augmented responses. Remarkably, CD21/35−/−CD19+/− and CD21/35−/−/CD19−/− mice generated normal or augmented TI-2 antibody responses. This data indicates that impaired responses to TI-2 antigens in CD21/35−/− mice are likely to be caused by elevated CD19 activity due to the absence of CD21/35 negative regulation. Thus, CD21/35 regulates CD19 expression and activity to promote optimal humoral responses to TI-2 antigens.

Limitations of polymerase chain reaction testing for diagnosing acute Epstein–Barr virus infections

Clinicians use molecular tests to detect Herpesviridae from blood without fully appreciating limitations of testing. Studies are needed to enhance our understanding of the impact of Herpesviridae latency on molecular testing. We retrospectively performed quantitative Epstein–Barr virus (EBV) on sera from patients between the ages of 1 and 30 who demonstrated serologic evidence of acute EBV ( n = 50) or remote EBV ( n = 50) infection. Epstein–Barr virus DNA was detected in 70% of acutely infected and 4% of remotely infected patients. Sera from acutely infected patients had higher EBV copy number than convalescent sera. Our results suggest that serology should be performed as the initial diagnostic test for acute EBV. The role for polymerase chain reaction in immunocompromised patients with impaired antibody responses or as a 2nd-line diagnostic test when serologic results are equivocal deserves further study.

Coexistence of (Partial) Immune Defects and Risk of Recurrent Respiratory Infections

Respiratory infections are major causes of morbidity and mortality, but determinants of susceptibility are poorly defined. We studied whether and to what extent immunologic and genetic factors are associated with increased susceptibility to respiratory infections. We evaluated the prevalence of IgA, IgM, IgG, and IgG subclass deficiencies, impairment in the antibody response against pneumococcal polysaccharides, G2m(n) allotypes, Fc gamma RIIa polymorphisms, partial C2 and partial C4 deficiency, promoter polymorphisms in MBL2, and lymphocyte subset deficiencies in a control population and in consecutive children with recurrent respiratory infections. IgA and/or IgG subclass deficiency was found in 27 of 55 patients (49%) and 6 of 43 controls (14%) (P = 0.0006). An impaired antibody response to polysaccharides was found in 7 patients (19%) and in 0 of 37 controls (P = 0.002). The Gm(n)marker was absent in 25 of 55 patients (45%) and 6 of 42 controls (14%) (P = 0.009). The MBL2 variants O/O, A/O, and A/A occurred in 9, 14, and 32 of the 55 patients, respectively, and in 1, 19, and 23 of the 43 controls, respectively (P = 0.05). There was no increase in the prevalence of partial C4 deficiency, C2 deficiency, lymphocyte subset deficiency, or Fc gamma RIIa polymorphism in the patients compared to the controls. A combination of at least 2 immune defects was found in 31 of 55 patients (56%) and in 4 of 42 controls (11.6%) (P <0.0001). Specific antipolysaccharide antibody deficiency, IgA and/or IgG subclass deficiency, Gm(n) allotype, and MBL2 genotype are susceptibility factors for recurrent respiratory infections, and coexistence of several immune defects is the strongest risk factor in this study.

Impaired specific antibody response and increased B-cell population in transient hypogammaglobulinemia of infancy

Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder with poorly understood pathophysiology. To better characterize THI and improve understanding of its pathophysiology. Twenty-four children with hypogammaglobulinemia defined by an IgG level less than 2 SDs below the mean on 2 occasions, who did not have other immunologic diagnoses, were followed and retrospectively reviewed. The average z-score for IgG level at presentation was -2.4 (mean age, 12 months; median age, 8 months), with a mean level of 254 mg/dL. Thirteen of 24 patients had IgA levels less than 2 SDs below the mean, 5 had IgM levels less than 2 SDs below the mean, and 7 of 23 had elevated IgE levels. Eighteen were followed up until their IgG levels normalized (mean age, 27 months; median age, 23 months), with 12 of 18 normalizing by 24 months and the remainder by 59 months. There was a significant association between presenting IgG z-score and duration of disease (P = .05). Five of the 18 patients had absolute CD19+ B-cell counts greater than the 95% percentile for age (P < .001), and the mean percentage and absolute CD19+ B-cell count across all patients were greater than those of the age-matched controls (P = .02). Most patients had nonprotective titers to Haemophilus influenzae type b vaccine, and one third had nonprotective titers to tetanus vaccine. Twenty patients carried at least one atopic diagnosis, and 13 of those had recurrent wheezing. THI is associated with a number of immunologic abnormalities beyond just hypogammaglobulinemia. These abnormalities include impaired specific antibody responses and increased proportions of CD19+ B cells and may be suggestive of particular immunologic mechanisms that result in hypogammaglobulinemia.

Effect of probiotics on vaccine antibody responses in infancy – a randomized placebo‐controlled double‐blind trial

Probiotics are immunomodulatory and may thus affect vaccine antibody responses. With the accumulating evidence of their health-promoting effects, probiotics are increasingly administered in allergy-prone infants. Therefore, we studied the effect of probiotics on antibody responses to diphtheria, tetanus and Haemophilus influenzae type b (Hib) vaccines in 6-month-old infants participating in a randomized placebo-controlled double-blind allergy-prevention trial. Mothers of unborn children at increased risk for atopy used a combination of four probiotic strains, or a placebo, for 4 wk before delivery. During 6 months from birth, their infants received the same probiotics and galacto-oligosaccharides, or a placebo. The infants were immunized with a DTwP (diphtheria, tetanus and whole cell pertussis) at ages 3, 4, and 5 months, and with a Hib polysaccharide conjugate at 4 months. Serum diphtheria, tetanus, and Hib IgG antibodies were measured at 6 months. In the probiotic group, protective Hib antibody concentrations (>/=1 microg/ml) occurred more frequently, 16 of 32 (50%) vs. six of 29 (21%) (p = 0.020), and the geometric mean (inter-quartile range) Hib IgG concentration tended to be higher 0.75 (0.15-2.71) microg/ml than in the placebo group 0.40 (0.15-0.92) microg/ml (p = 0.064). In these respective groups, diphtheria, 0.38 (0.14-0.78) vs. 0.47 (0.19-1.40) IU/ml (p = 0.449), and tetanus, 1.01(0.47-1.49) vs. 0.81 (0.56-1.39) IU/ml (p = 0.310), IgG titers were comparable. In conclusion, in allergy-prone infants probiotics seem not to impair antibody responses to diphtheria, tetanus, or Hib, but may improve response to Hib immunization.

Mutations in TNFRSF13B Encoding TACI Are Associated With Common Variable Immunodeficiency in Humans

&amp;gt;Purpose of the Studies.To search for mutations of TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor; also TNFRSF13B) in patients with common variable immunodeficiency (CVID) and immunoglobulin A deficiency (IGAD).Study Populations.Salzer et al screened 162 unrelated individuals with CVID. Castigli et al studied 19 unrelated individuals with CVID and 16 with IGAD. Healthy individuals (100 and 50, respectively) served as controls.Methods.Genomic DNA from patients was subjected to reverse transcription and polymerase chain reaction sequencing analysis of the 5 exons of the gene encoding TACI. Binding of mutant TACI to ligands and stimulation of immunoglobulin production in vitro with TACI agonists in patients was also studied.Results.Salzer et al identified 13 individuals with CVID who had mutations in TACI. Castigli et al identified 4 individuals with CVID and 1 with IGAD and TACI mutations. None of the 150 controls studied had any of the identified TACI mutations. Interestingly, TACI mutations could cause disease in both the heterozygous and homozygous conditions. Patients’ cells had diminished binding to TACI ligands and showed diminished responses (immunoglobulin production) to TACI agonists in vitro. The clinical characteristics of the patients included hypogammaglobulinemia and impaired antibody responses, recurrent bacterial sinopulmonary infections, autoimmune disease (anemia, thyroiditis, positive antinuclear antibody), lymphoproliferative disease, and malignancy (B-cell lymphoma, gastric carcinoma).Conclusions.Approximately 8% to 20% of patients with severe combined immunodeficiency or IGAD may have heterozygous or homozygous mutation in TACI. This genetic alteration should be sought in patients with these disorders.Reviewer Comments.CVID and IGAD are among the most prevalent humoral immunodeficiencies at all ages. These studies represent important descriptions of defined mutations in patients with CVID and IGAD occurring in a significant fraction of these patients in 2 relatively genetically disparate populations. The ability to clearly define the underlying cause of disease in these patients will immediately lead to greater accuracy and confidence in diagnosis, earlier and more aggressive therapy, and, hopefully, improved outcomes.

Use of intravenous immunoglobulin in human disease: A review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology

Human immunoglobulin prepared for intravenous administration (IGIV) has a number of important uses in the treatment of disease. Some of these are in diseases for which acceptable treatment alternatives do not exist. In this review we have evaluated the evidence underlying a wide variety of IGIV uses and make specific recommendations on the basis of these data. Given the potential risks and inherent scarcity of IGIV, careful consideration of the indications for and administration of IGIV is warranted.

Antibody Response to Hepatitis B Vaccine in End-Stage Renal Disease Patients

Background: This retrospective and comparative study evaluated the relationship between different factors which may contribute to suboptimal immunological response to intramuscular recombinant hepatitis B vaccine in end-stage renal disease (ESRD) subjects. Methods: From a cohort of 64 dialysis subjects undergoing primary vaccination with Engerix-B^®, we determined the predictive factors that impinged on patients’ response to vaccine, as defined by anti-HBs level ≧10 mIU/l. Dose efficacy was further evaluated by comparing three historical cohorts vaccinated by the regimens of 20, 40 and 80 µg/dose, respectively. Results: We identified 64 ESRD patients (mean age 43 ± 12 years, 81% receiving peritoneal dialysis) who received primary vaccination from April 1997 to September 2004. Median follow-up was 6.5 years. They achieved 81% seroconversion rate. Older age, diabetes mellitus, obesity and low Engerix-B dose were risk factors of inadequate anti-HBs response by univariate analysis. By stepwise logistic regression analysis, hepatitis B vaccine dose was the only independent predictive factor of impaired antibody response. An Engerix-B vaccine dose of 20 µg was associated with more than tenfold increase in risk of non-response to hepatitis B vaccine (hazards ratio 32.2 (95% CI 3.85–250.0)). Immunization with 80 µg of Engerix-B increased the likelihood of persistent protective antibody (log-rank test, p = 0.014). Immunization with Engerix-B 80-µg dose is estimated to prevent one extra ESRD subject who would lose seroprotective anti-HBs level at 1 year for every 5.6 patients treated (number needed to treat to benefit, 5.6 (95% CI 5.4–5.8)). Conclusions: Our results suggest the potential for the three-dose schedule of recombinant vaccine Engerix-B 80 µg to prolong the immune response among ESRD population.

The Clinical Syndrome of Specific Antibody Deficiency (SAD) in Children

RATIONALE: SAD is an immune deficiency characterized by normal immunoglobulin levels and antibody responses to protein antigens but impaired antibody responses to polysaccharide antigens. The prevalence of SAD and its clinical features are not well established.

TLR Signaling in Adaptive Immune Responses

Toll-like receptors (TLRs), which recognize pathogen-associated motifs and play a key role in initiating innate immune responses, have also been implicated in maturation of dendritic cells and thereby in T helper (T H ) cell activation. Whether TLRs play a direct role in B cell activation has been unclear. Pasare and Medzhitov found that mice lacking the TLR signaling adaptor MyD88 (myeloid differentiation primary response gene 88) showed impaired immunoglobulin (Ig) G1 and IgG2 antibody responses to T-dependent antigens and lower steady-state levels of IgM, IgG1, IgG2c, and IgG3 than those in wild-type mice. Because impaired B cell responses could result from inadequate T H activation, the authors tested the direct role of TLR signaling in B cells by transferring B cells from wild-type or knockout mice into a strain of mice that lack mature B cells. Antigen-specific production of IgG and IgM was impaired in mice that received B cells lacking MyD88 or TLR4 compared with that in mice receiving wild-type B cells and, following immunization, these mice had a lower percentage of B cells that were positive for a germinal center marker. Furthermore, immunization of transgenic mice that expressed MyD88 in dendritic cells but not in B cells led to functional T H 1 responses but not to antigen-specific antibody production. Moreover, TLR ligation enhanced the processing of antigen taken up through B cell receptor-mediated endocytosis. Thus, TLR signaling appears to play a direct role in T-dependent antigen-specific B cell responses in addition to its effects on T H activation and thus T cell help. The IgE response (which is initiated by parasites) was similar in mice receiving B cells lacking MyD88 to that in mice receiving wild-type B cells, which suggests that TLR signaling in B cells may help identify the microbial origin of antigens and thereby direct the B cell response. C. Pasare, R. Medzhitov, Control of B-cell responses by Toll-like receptors. Nature 438 , 364-368 (2005). [PubMed]

Impaired Immune Responses and Prolonged Allograft Survival in Sly1 Mutant Mice

Adaptive immunity is crucial for protective host defense and the development of immunological disorders. SLY1 was recently identified as an X-chromosomal SH3 protein that is serine phosphorylated (Ser27) upon B-and T-cell receptor engagement. Here, we demonstrate that SLY1 is localized in the cytoplasm and the nucleus of immunocytes. We generated mice expressing a mutant version of SLY1 lacking Ser27 and a functional nuclear localization signal. The defective SLY1 (SLY1(d)) protein is localized exclusively in the cytoplasm. B- and T-cell proliferation is attenuated and T-cell cytokine production is severely reduced. Sly1(d/d) mice exhibit reduced lymphoid organ sizes, diminished marginal zone B-cell numbers, and severely impaired antibody responses against T-dependent and -independent antigens. Importantly, survival of semi-identical cardiac allografts was substantially prolonged in Sly1(d/d) mice. These results define SLY1 as an essential molecular component for the full activation of adaptive immunity.

Antibody deficiency in bronchiectasis

To the Editors: We have read with interest the article by van Kessel et al . 1 on impaired antibody response to the pneumococcal polysaccharides of Streptococcus pneumoniae in patients with bronchiectasis of unknown aetiology. Several aspects of this work are controversial and there is no unanimous agreement on some of their conclusions. The first aspect that merits attention is the lack of a control group to establish the normal total antibody response and the isotypes to the vaccine, and, consequently, the diagnostic criteria of impaired antibody response. There are no universal criteria for adequate antibody response to polysaccharides and each laboratory should establish its own 2. This is particularly important because of the therapeutic implications. Treatment of symptomatic patients with a lack of antibody response is performed with periodic administration of intravenous immunoglobulins (Ig) at a high cost, dependent on healthcare centres and potential side-effects 3. For this reason, strict diagnostic criteria must be established. It is interesting to note that van Kessel et al . 1 used different criteria for the response with total antibodies to the serotypes 3, 4 and 9V, in which the post-vaccination titre should be >20 U·mL−1 with at least a two-fold increase for two of the three …

Vector-primed mice display hypo-responsiveness to foreign antigen presented by recombinant Salmonella regardless of the route of delivery

Our previous studies have shown that mice which have been orally primed with an attenuated Salmonella vector [ S. enterica serovar Stanley] are hypo-responsive to foreign antigens later delivered orally by the same vector strain, responding with significantly impaired serum and intestinal antibody responses compared with those seen in unprimed controls. Initial vector priming of the gut-associated lymphoid tissue (GALT) is likely to result in impaired persistence of recombinant Salmonella later administered orally. Delivery of recombinant bacteria by the intra-peritoneal or intra-nasal route, to avoid exposure to a primed GALT, did not allow vector-primed recipients to mount normal antibody responses to the foreign pilus protein K88. The negative impact of vector priming could be largely overcome, however, if mice were exposed to the foreign protein just prior to priming with the vector strain. Using this strategy, vector-primed mice displayed normal gut IgA and intermediate serum IgG responses to K88 following oral administration of recombinant Salmonella. Our findings are compatible with the concept of epitopic suppression, in which failure to respond to the foreign vaccine antigen reflects the clonal dominance of B cells specific for epitopes associated with the vector strain.

Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology

As a defective anti-polysaccharide response can exist in the absence of an immunoglobulin deficiency, a series of 26 patients with bronchiectasis of unknown aetiology was vaccinated with a 23-valent pneumococcal polysaccharide vaccine. All patients suffered from recurrent respiratory tract infections. When measuring total antibody levels to pneumococcal serotypes 3, 4 and 9, a normal polysaccharide antibody response was found in 22 patients. However, only 11 of these subjects showed a normal pneumococcal antibody response within the IgA and/or IgG2 subclass, and thus could be classified as true responders, while 15 patients did not respond in either the IgA class or in the IgG2 subclass. When analysing differences between the responder (n = 11) and nonresponder (n = 15) groups, the latter demonstrated higher frequencies of respiratory tract infections and more severe lung pathology, as revealed by the presence of more bronchi visualised in the peripheral third of the lung by high-resolution computed tomography scanning. Moreover, nonresponders needed extensive lung surgery more often in order to control their disease (number of resected segments eight versus five). In conclusion, an important fraction of patients presenting with idiopathic bronchiectasis is associated with a selective anti-polysaccharide response deficiency and this subgroup appears to represent a more severe clinical phenotype. Therefore, it can be regarded as a separate clinical entity with possible therapeutic targets. In order to identify IgA and IgG2 anti-polysaccharide nonresponders, all patients presenting with bronchiectasis of unknown aetiology should be immunised with a pneumococcal polysaccharide vaccine, and IgA and IgG2 isotype responses should be evaluated as well as the total antibody response.

Protective antibody responses to pneumococcal conjugate vaccine after autologous hematopoietic stem cell transplantation

Patients undergoing autologous hematopoietic stem cell transplantation (autoHCT) are at increased risk for infection with Streptococcus pneumoniae and have impaired antibody responses to pneumococcal polysaccharide vaccines. We performed this study to examine the ability of autoHCT patients to respond to a heptavalent pneumococcal conjugate vaccine (PCV7) given after transplantation and to determine whether there was a potential benefit of immunizing these patients before stem cell collection. Sixty-one patients scheduled for autoHCT were randomized to receive either PCV7 or no vaccine before stem cell collection. After stem cell reinfusion, all study patients were immunized with PCV7 at 3, 6, and 12 months. Pneumococcal immunoglobulin G antibody concentrations were measured at the time of each immunization and 1 month after the 12-month dose. Serotype-specific pneumococcal antibody concentrations were significantly higher in patients immunized with PCV7 before stem cell collection compared with patients not immunized before their stem cells were collected for 6 of 7 serotypes at 3 months, 6 of 7 serotypes at 6 months, 4 of 7 serotypes at 12 months, and 3 of 7 serotypes at 13 months. After the 3-dose series of PCV7 after autoHCT, >60% of study patients had protective concentrations of antibody to all 7 vaccine serotypes regardless of immunization before stem cell collection. Pneumococcal conjugate vaccine is immunogenic in autoHCT patients and may be an effective strategy to prevent invasive disease after transplantation.