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Prophylactic antibiotics (PA) and immunoglobulin replacement (IGRT) are commonly used in specific antibody deficiency (SAD); however, optimal treatment is not well-established. Our purpose is to compare treatment outcomes with IGRT and/or PA among SAD patients. A retrospective chart review of SAD patients treated at two tertiary centers between January 2012 and May 2017 was performed. Clinical and laboratory data, and rates of infections prior to and after treatment with IGRT or PA were analyzed. Descriptive analyses, between-group comparisons of rates of infection after 1 year of treatment, and a stepwise logistic regression model were employed to explore factors contributing to treatment outcomes. We identified 65 SAD patients with mean age were 18 years (2–71 years). The baseline mean number of infections in the PA group and IGRT group was 4.71 (SD 3.15) and 7.73 (SD 6.65), respectively. Twenty-nine (44.6%) received IGRT, 7 (10.7%) received PA, 7 (10.7%) received both IGRT and PA, 15 (23.1%) failed PA and switched to IGRT, and 7 did not receive any specific treatment. After 1 year of treatment, the difference in the mean number of infections in PA vs. IGRT was not statistically significant [2.86 (2.73) vs. 4.44 (4.74), p = 0.27]. Reporting autoimmunity increased the odds for persistent infections (OR = 4.29; p = 0.047), while higher IgG levels decreased the odds for persistent infections (OR = 0.68, p = 0.018). PA and IGRT are equally effective as first line in preventing infections in SAD patients. However, patients who fail PA would benefit from IGRT.

Specific antibody deficiency against pneumococcal serotypes was detected in a patient with recurrent episodes of fever. A 21-year-old man presented with a two-month history of recurrent episodes of fever and shaking chills. He was diagnosed with recurrent episodes of pneumonia caused by Streptococcus pneumoniae serotype 19A and treated with amoxicillin. Serotype-specific antibodies were not produced against most of the serotypes, which were consistent with moderate specific antibody deficiency. After pneumococcal 13-valent conjugate vaccination and pneumococcal polysaccharide vaccination, he adequately responded to the infecting serotype with an antibody titer of 1.1 µg/mL. There were eventually no recurrent episodes of fever with pneumonia.

Background. In the recent coronavirus disease 2019 (COVID-19) pandemic, millions of people have been affected so far. Clinical manifestations and natural history of infections have a very wide range, which is important to know it in various underlying diseases. Although children are less affected than adults, its presentation especially in those with underlying diseases should not be neglected.Case presentation. Herein we report the first case of specific antibody deficiency, who was affected with COVID-19. The patient suffered from rhinorrhea and modestly increased in productive cough, but real-time reverse transcription polymerase chain reaction was positive for COVID-19.Conclusions. Although presentation of COVID-19 in patients with immunodeficiency could be mild, it should not be missed, while early diagnosis and appropriate treatment can survive affected patients.

To summarize the pitfalls associated with defining exactly what constitutes an "impaired" antibody response to polysaccharide antigens and the importance of documenting actual pyogenic infections before making a diagnosis of an immune deficiency. Specific antibody deficiency is an immune deficiency defined by the presence of normal quantitative levels of immunoglobulins, but impaired antibody responses to polysaccharide antigens, in patients presenting with frequent otosinopulmonary infections with pyogenic bacteria.PubMed review using the following keywords: specific antibody deficiency, pneumococcal vaccination, Salmonella vaccination, infectious sinusitis.This review focused on key studies that have been utilized to define what constitutes a "normal" humoral immune response to pneumococcal and Salmonella vaccination in healthy subjects and on published studies defining current expert opinion.Published studies demonstrate wide variability in response to pneumococcal vaccination in healthy individuals, making it daunting to define what constitutes an abnormal response. These challenges are exacerbated by striking laboratory variability in reporting results.Clinical examinations in individuals with self-reported recurrent acute sinusitis or lower respiratory infections need to document an infectious etiology with pyogenic bacteria and must rule out an underlying primary airway inflammatory disorder before consideration is made regarding the presence of an immune deficiency. In addition, decision making regarding diagnosis and treatment of patients who are examined for humoral immunodeficiency should not hinge solely on the strict application of defined cutoffs for "normal" response to a single polysaccharide vaccine, but rather a global assessment of humoral immune function in the context of the clinical presentation.

Background:Inadequate titers of pneumococcal antibody (PA) are commonly present among patients with recurrent respiratory infections. Objective:We sought to determine the effect of the degree of inadequacy in baseline PA titers on the subsequent polysaccharide vaccine response, the incidence of sinusitis, and allergic conditions. Methods:A total of 313 patients aged 6 to 70 years with symptoms of recurrent respiratory infections were classified by baseline-pPA (percentage of protective [≥1.3 µg/mL] PA serotypes/total tested serotypes) and postvaccination pPA (post-pPA): Group A (adequate baseline-pPA), Group B (inadequate baseline-pPA, adequate post-pPA, responders), and Group C (inadequate baseline-pPA, inadequate postpPA, nonresponders, specific antibody deficiency [SAD]). Immunity against Streptococcus pneumoniae was defined as adequate when the pPA was ≥70%. Each group and combined groups, Group AB (inadequate baseline-pPA), and Group BC (adequate post-pPA) were analyzed for demographics, history of sinusitis, recurrent sinusitis in the following year, allergic conditions, and association with inadequate individual serotype titers. Results:Over 80% of patients with respiratory symptoms had inadequate baseline-pPA. Baseline-pPA and SAD prevalence are inversely related (odds ratio = 2.02, 95% CI: 1.15-3.57, P = .01). Inadequate serotype 3 antibody titer is highly associated with SAD (odds ratio = 2.02, 96% CI: 1.61-5.45, P

J Hajjar, AL Nguyen, G Constantine. J Clin Immunol. 2020;40:158–164 To compare treatment outcomes in patients with specific antibody deficiency (SAD) who were treated with immunoglobulin replacement therapy (IGRT) and/or prophylactic antibiotics (PA). This study included 65 patients with SAD (mean age 18, range 2–71 years old) who were treated with IGRT and/or PA at two tertiary care centers in the United States. This was a retrospective chart review that evaluated clinical characteristics, laboratory findings, treatment patterns and clinical outcomes of patients with SAD who were treated with IGRT and/or PA. All patients were followed …

Background Specific antibody deficiency (SAD) is highly associated with chronic rhinosinusitis (CRS) and is defined by inadequate post-vaccination percentage of protective (≥1.3 ug/mL) pneumococcal antibody serotypes divided by total tested serotypes (post-pPA). Objective Although Methods 203 patients aged 6 to 70 years with CRS were classified, retrospectively by pre-vaccination pPA (pre-pPA) and post-pPA by two different criteria. Using 70% as the threshold for adequate pneumococcal antibody (PA) response, patients were classified as: Group A (adequate pre-pPA), Group B (inadequate pre-pPA, adequate post-pPA), Group C (inadequate pre-pPA, inadequate post-pPA, SAD). Using 50% as the threshold, patients were similarly classified as: Group A’, B’ and C’. Results The recurrence rate of sinusitis during the next one year in Group A (pre-pPA ≥70%) was significantly less than that of Group A’ (pre-pPA ≥50%) (10% vs. 34%, P = .03). Group A had lower incidence of sinusitis than Group B (pre-pPA Conclusion Employment of a 70% pPA threshold for SAD in comparison to a 50% threshold would decrease the incidence of sinusitis in the next one year by vaccinating patients in 51–69% pPA range. Pre-existing PAs (Group A) yielded a higher protection against sinusitis than vaccine-acquired antibodies (Group B).

Background: Specific antibody deficiency is a primary immunodeficiency characterized by normal immunoglobulins with an inadequate response to polysaccharide antigen vaccination. This disease can result in recurrent infections, the most common being sinopulmonary infections. Treatment options include clinical observation, prophylactic antibiotic therapy, and immunoglobulin supplementation therapy, each with limited clinical data about their efficacy. Objective: This study aimed to identify whether there was a statistically significant difference in the rate of infections for patients who were managed with clinical observation, prophylactic antibiotics, or immunoglobulin supplementation therapy. Methods: A retrospective chart review was conducted. Patients were eligible for the study if they had normal immunoglobulin levels, an inadequate antibody response to polysaccharide antigen‐based vaccination, and no other known causes of immunodeficiency. Results: A total of 26 patients with specific antibody deficiency were identified. Eleven patients were managed with immunoglobulin supplementation, ten with clinical observation, and five with prophylactic antibiotic therapy. The frequency of antibiotic prescriptions was assessed for the first year after intervention. A statistically significant rate of decreased antibiotic prescriptions after intervention was found for patients treated with immunoglobulin supplementation (n = 11; p = 0.0004) and for patients on prophylactic antibiotics (n = 5; p = 0.01). There was no statistical difference in antibiotic prescriptions for those patients treated with immunoglobulin supplementation versus prophylactic antibiotics (p = 0.21). Conclusion: Prophylactic antibiotics seemed to be equally effective as immunoglobin supplementation therapy for the treatment of specific antibody deficiency. Further studies are needed in this area.

Specific antibody deficiency is a primary immunodeficiency disease recognized by the International Union of Immunology Societies and defined by recurrent respiratory infections with normal immunoglobulins, but diminished antibody responses to polysaccharide antigens after vaccination with the 23 valent pneumococcal polysaccharide vaccine. Clinical immunologists struggle with diagnosis and treatment, because the definition of an adequate response to immunization remains controversial. Specific antibody deficiency is managed clinically with close follow-up and prompt treatment of infections, antibiotic prophylaxis, or immune globulin therapy. Treatment is individualized using clinical judgment and existing practice guidelines, which will likely evolve as more studies become available.

Specific antibody deficiency (SAD) is a primary immunodeficiency disease characterized by normal immunoglobulins (Igs), IgA, IgM, total IgG, and IgG subclass levels, but with recurrent infection and diminished antibody responses to polysaccharide antigens following vaccination. There is a lack of consensus regarding the diagnosis and treatment of SAD, and its clinical significance is not well understood. Here, we discuss current evidence and challenges regarding the diagnosis and treatment of SAD. SAD is normally diagnosed by determining protective titers in response to the 23-valent pneumococcal polysaccharide vaccine. However, the definition of an adequate response to immunization remains controversial, including the magnitude of response and number of pneumococcal serotypes needed to determine a normal response. Confounding these issues, anti-polysaccharide antibody responses are age- and probably serotype dependent. Therapeutic strategies and options for patients with SAD are often based on clinical experience due to the lack of focused studies and absence of a robust case definition. The mainstay of therapy for patients with SAD is antibiotic prophylaxis. However, there is no consensus regarding the frequency and severity of infections warranting antibiotic prophylaxis and no standardized regimens and no studies of efficacy. Published expert guidelines and opinions have recommended IgG therapy, which are supported by observations from retrospective studies, although definitive data are lacking. In summary, there is currently a lack of evidence regarding the efficacy of therapeutic strategies for patients with SAD. We believe that it is best to approach each patient as an individual and progress through diagnostic and therapeutic interventions together with existing practice guidelines.

Fecal microbial transplantation (FMT) has been shown to be more effective than antimicrobial therapy in the treatment of recurrent Clostridium difficile infection (CDI) in adults, with a randomized control trial (RCT) showing resolution of symptoms and clearance of CDI in 81% of subjects compared to 31% with standard antibiotic therapy (1). This article is protected by copyright. All rights reserved.

Background Specific antibody deficiency may predispose patients to recurrent respiratory tract infections. There is limited literature assessing specific antibody deficiency in chronic rhinosinusitis (CRS). This study evaluated the role of specific antibody deficiency in patients with CRS who have failed medical therapy. Methods We performed a retrospective chart review of patients with CRS who underwent functional endoscopic sinus surgery and had prior assessment for humoral immunodeficiency. Each patient's record was reviewed for serum quantitative immunoglobulin G (IgG) and IgA and anti–Streptococcus pneumoniae antibody titers measured at baseline and 6 weeks postvaccination with the 23-valent unconjugated pneumococcal vaccine. Clinical characteristics, including asthma, atopy, and nasal polyps, were recorded. Results Of the 129 CRS patients who met inclusion criteria, 93 (72%) had low baseline antipneumococcal titers. Fifteen (11.6%) patients were diagnosed with specific antibody deficiency based on an inadequate response to the pneumococcal polysaccharide vaccine. The group of patients with specific antibody deficiency had significantly lower serum IgA levels when compared with those patients with normal preimmunization titers (138 ± 67.3 versus 330 ± 356; p < 0.05). Patients with specific antibody deficiency had a significantly lower number of preimmunization protective antipneumococcal titers when compared with vaccine responders (1.41 versus 2.72; p < 0.0005. Conclusion This retrospective study indicates that patients with medically refractory CRS may have a high prevalence of low preimmunization antipneumococcal titers and specific antibody deficiency. Furthermore, lower serum IgA levels identified in these specific antibody deficiency patients suggests that a prospective study to further characterize this relationship is warranted.

Exuberant gingival inflammation accompanied by periodontitis is a rare finding in a very young child and may indicate a defect in the host response. Affected children should be referred to appropriate specialists to establish a definitive diagnosis. A 5-year-old girl presented with persistent gingival inflammation and periodontal destruction. Immunological investigations identified specific polysaccharide antibody deficiency which, when treated, resulted in a significant improvement in the gingival condition. This case illustrates the need for integrated management by a wide range of dental and medical specialists. Antibody deficiency is rare but, if not identified and treated effectively, can be associated with chronic ill health and decreased life expectancy. CPD/Clinical Relevance: This article describes a rare case of gingival inflammation accompanied by periodontitis in a very young child secondary to an underlying host antibody deficiency and details the investigation, management and clinical outcomes.

Despite the increased identification of specific antibody deficiency (SAD) in chronic rhinosinusitis (CRS), little is known about the relationship between SAD severity and the severity and comorbidities of CRS. The prevalence of an impaired antibody response in the general population is also unknown.The objective of this study was to determine if the SAD severity stratification applies to real-life data of patients with CRS.An electronic health record database was used to identify patients with CRS evaluated for humoral immunodeficiency with quantitative immunoglobulins and Streptococcus pneumoniae antibody titers before and after pneumococcal vaccine. SAD severity was defined, according to the guidelines, based on the numbers of titers ≥1.3 μg/dL after vaccination: severe (≤2 serotypes), moderate (3-6 serotypes), and mild (7-10 serotypes). Comorbidities and therapeutic response were assessed. The prevalence of an impaired antibody response in a normal population was assessed.Twenty-four percent of the patients with CRS evaluated for immunodeficiency had SAD, whereas 11% of a normal population had an impaired immune response to polysaccharide vaccination (P.05). When evaluated by the practice parameter definition, 239 of 595 (40%) met the definition of SAD. Twenty-four (10%) had severe SAD, 120 (50%) had moderate SAD, and 95 (40%) had mild SAD. Patients with moderate-to-severe SAD had worse asthma, a greater likelihood of pneumonia, and more antibiotic courses in the 2 years after vaccination than patients with mild SAD.This study provides real world data supporting stratification of SAD by severity, demonstrating a significant increase in the comorbid severity of asthma and infections in CRS patients with moderate-to-severe SAD compared with those with mild SAD and those without SAD.

Prophylactic antibiotics (PA) and immunoglobulin replacement (IGRT) are commonly used in specific antibody deficiency (SAD); however, optimal treatment is not well-established. Our purpose is to compare treatment outcomes with IGRT and/or PA among SAD patients.A retrospective chart review of SAD patients treated at two tertiary centers between January 2012 and May 2017 was performed. Clinical and laboratory data, and rates of infections prior to and after treatment with IGRT or PA were analyzed. Descriptive analyses, between-group comparisons of rates of infection after 1 year of treatment, and a stepwise logistic regression model were employed to explore factors contributing to treatment outcomes.We identified 65 SAD patients with mean age were 18 years (2-71 years). The baseline mean number of infections in the PA group and IGRT group was 4.71 (SD 3.15) and 7.73 (SD 6.65), respectively. Twenty-nine (44.6%) received IGRT, 7 (10.7%) received PA, 7 (10.7%) received both IGRT and PA, 15 (23.1%) failed PA and switched to IGRT, and 7 did not receive any specific treatment. After 1 year of treatment, the difference in the mean number of infections in PA vs. IGRT was not statistically significant [2.86 (2.73) vs. 4.44 (4.74), p = 0.27]. Reporting autoimmunity increased the odds for persistent infections (OR = 4.29; p = 0.047), while higher IgG levels decreased the odds for persistent infections (OR = 0.68, p = 0.018).PA and IGRT are equally effective as first line in preventing infections in SAD patients. However, patients who fail PA would benefit from IGRT.

The prevalence and clinical significance of specific polysaccharide antibody deficiency (SAD) in children are poorly understood. The authors sought to determine the prevalence of SAD in children with chronic wet cough, through a retrospective study of all children with chronic wet cough attending our tertiary respiratory clinic over a 12-month period. Antibody levels to 13 pneumococcal serotypes were measured following vaccination with the unconjugated pneumococcal polysaccharide vaccine, Pneumovax II, and clinical data were reviewed. Twenty-four children over 2 years of age with chronic wet cough were vaccinated. Fourteen (58%) failed to mount an adequate antibody response, consistent with SAD. Children with SAD were more likely than children with normal antibody responses to require intravenous antibiotics (p=0.035) and to have abnormal chest radiographs (p=0.029). The authors conclude that SAD is present in a significant number of children with chronic wet cough. The clinical significance and long-term outcome of SAD warrant further investigation in prospective studies.

Purpose Specific antibody deficiency (SAD) involves a deficient response to a polysaccharide vaccine despite having normal immunoglobulin levels. The failure of the polysaccharide response can be observed as a component of various primary antibody deficiencies. However, only a few studies have described the clinical and immunological profiles in SAD and/or other primary immunodeficiencies (PIDs) in adults. Methods A total of 47 patients who had a clinical history suggestive of antibody deficiency or had already been diagnosed with various antibody deficiencies were enrolled. Polysaccharide responses to 7 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) were measured using the World Health Organization enzyme-linked immunosorbent assay (WHO-ELISA), and postvaccination immunoglobulin G (IgG) titers were compared to clinical and laboratory parameters. Results Based on the American Academy of Allergy, Asthma, and Immunology (AAAAI) criteria for the WHO-ELISA, 11 (23.4%) patients were diagnosed as having SAD. Sixteen-three percent of them had combined with other types of PID, such as IgG subclass deficiency and hypogammaglobulinemia. Postvaccination IgG titers for the serotypes 4/9V/18C correlated with IgG2 (P = 0.012, P = 0.001, and P = 0.004) and for 6B/9V/14 with IgG3 (P = 0.003, P = 0.041, and P = 0.036, respectively). The IgG3 subclass levels negatively correlated with forced expiratory volume in 1 second (FEV1, %) and FEV1/forced vital capacity (P < 0.001 and P = 0.001, respectively). Conclusion SAD can be diagnosed in patients with normal IgG levels as well as in those deficient in IgG or the IgG3 subclass, implicating that restricted responses to Streptococcus pneumoniae polysaccharide antigens commonly exist in patients with predominantly antibody deficiency.

Background Response to polysaccharide antigens is a test to evaluate the immunological competence of children with recurrent respiratory infections (RRI) of unknown cause and no other immune system abnormality. In order to detect specific antibody deficiency (SAD), a group of children with RRI without other immunodeficiency were prospectively studied. Methods We included 20 children (12 male), age range 3–14 years, with six or more annual episodes of respiratory infections (RI); one or more monthly episodes of RI during the winter months; or three or more annual episodes of lower RI. The children were immunised with 23-valent polysaccharide anti-pneumococcal vaccine, and ELISA was used to measure anti-polysaccharide IgG antibody levels for 10 pneumococcal serotypes at baseline (T0), and 45 days (T1) and one year post-immunisation (T2). Post-immunisation response above 1.3 μg/ml for more than 50% of the serotypes was considered normal for children 2–5 years, and for more than 70% of the serotypes in children older than 5 years. Results At T1 19/20 children showed a normal response for their age, and only one patient showed a deficient response, suggestive of classic moderate SAD. At T2, 8/20 patients showed deficient responses, suggestive of impaired persistence of specific antibodies. There was a noteworthy association between deficient response and asthma and allergic rhinitis. Conclusions We propose first ruling out local or systemic causes, then performing serum immunoglobulin IgM, IgG, IgA, IgE and IgG subclass levels, and finally measuring response to polysaccharide pneumococcal antigens for detection of SAD.

Purpose: Recent studies have reported that CD19+CD20+CD27+CD43+CD70-CD5− B cells produce IgG, IgA, and IgM antibodies to Streptococcus pneumoniae (Spn). In one adult patient with specific antibody deficiency (SAD), the percentage of CD5− CD19+CD20+CD27+CD43+CD70− B cells was decreased. The percentages of CD5−of CD19+CD27+CD43+CD70− B cells in children with SAD were examined in this study. Methods: Clinical and immunologic studies were obtained from a review of medical records. The percentages of CD5− of CD19+CD27+CD43+CD70− B cells were determined by flow cytometry. Results: Patients with SAD had significantly decreased percentages of CD5− of CD19+CD27+CD43+CD70− B cells. There was a significant correlation between decreased percentage of CD5−of CD19+CD27+CD43+CD70− B cells and decreased percentage of protective antibody titers to Spn. Conclusion: Decreased percentage of CD5− of CD19+CD27+CD43+CD70− B cells were identified in patients with SAD and correlated with decreased antibody responses to Spn.

Specific antibody deficiency (SAD) with normal immunoglobulin and normal B cells is a primary immunodeficiency characterized by reduced ability to produce antibodies to specific antigens especially polysaccharides.To describe the characteristics of patients diagnosed with SAD emphasizing the association between primary immunodeficiency and allergic diseases.Descriptive study showing patients with SAD treated at a public hospital between August 2007 and July 2015. Other secondary or primary immunodeficiency was discarded. The diagnosis of SAD was based on recurrent infections and abnormal response to pneumococcal polysaccharide vaccine assessed by specific IgG to 10 pneumococcal serotypes.Twelve patients were included, 4 males, mean age 6 years, recurrent pneumonia predominated (91.7%) as well as other respiratory and invasive infections. All patients with SAD had associated asthma, 11 had allergic rhinitis, and other allergies. Three patients did not respond to any of the 10 serotypes contained in pneumococcal polysaccharide vaccine, and those who responded were with low titers. Treatment with conjugate pneumococcal vaccine was favorable in 11/12 patients.In children older than 2 years with recurrent respiratory infections or invasive S. pneumoniae infections with normal immunoglobulin we recommend to investigate SAD, especially if they have a concurrent allergic disease.

SummarySeveral T cell abnormalities have been described in common variable immunodeficiency (CVID), a B cell disorder of mainly unknown origin. A subset of CVID patients suffers from frequent reactivations of herpes viruses. We studied T cell function in CVID [and in a subset of paediatric patients with specific antibody deficiency (SAD)] by measuring T cell proliferation and cytokine production in response to herpes virus-antigens in paediatric CVID patients (n = 9) and paediatric SAD patients (n = 5), in adult CVID patients (n = 14) and in healthy controls. Paediatric CVID patients, but not SAD patients, displayed moderately increased CD8+ T cell proliferation in response to cytomegalovirus, human herpes virus type 6B (HHV6-B) and herpes simplex virus compared to controls. CD8+ T cell responses in adult CVID patients tended to be increased in response to cytomegalovirus and herpes simplex virus. In response to stimulation with herpes virus antigens, the proinflammatory cytokines interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and interferon inducible protein (IP)-10 were produced. Overall, no major differences were detected in cytokine production upon stimulation between patients and controls, although higher IL-10 and IL-12 production was detected in paediatric patients. In conclusion, cellular immunity against herpes virus antigens appears undisturbed in CVID patients, although defects in subpopulations of CVID patients cannot be excluded.

The nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-κB1) is a master regulator of immune and inflammatory responses.[1][1],[2][2] NF-κB1 belongs to the NF-κB/Rel family of transcription factors that consists of five members in humans: NF-κB1 (p105/p50), NF-κB2 (p100/p52

Introduction Recurrent exacerbations are a characteristic feature of uncontrolled asthma, often due to viral or bacterial infections. We have reported in a retrospective study that immune deficiency is common in asthma and correlates with reduced lung function. We set up a prospective study to determine if this predisposes to a more severe disease. Aim Our aim is to ascertain if immune deficiency is associated with a more severe disease potentially with radiological changes and clinically with low lung function and frequent exacerbations. Methods We prospectively collected data from new patients attending the regional asthma and fungal clinics. Demographics, markers of disease severity and specific antibody levels to Haemophilus iInfluenzae (HI), and Streptococcus pneumoniae (SP), were recorded. Patients with specific antibody deficiency (HI: ≤ 0.15 iu and SP: ≤ 0.35 iu to 6+ of 12 strains tested) received appropriate vaccination(s) in primary care (Pneumovax® and Meniotrix®), with repeat samples collected two months later. We also recorded blood and sputum eosinophil counts, radiological findings such as bronchiectasis and bronchial wall thickening, total IgE, smoking status, exacerbations in the last year and ITU admissions. Results 101 patients were followed up (69 asthma, 32 fungal) 67 female, mean (SD) age 53 (15) years, FEV1 69 (21.9)% predicted, ICS dose 1818 (1244) μg, and BMI 29.9 (8.9) kg/m 2 . Specific antibody levels and responses to vaccination are presented in Figure 1. Immune deficiency at baseline and post vaccination did not correlate with lung function, radiological findings such as bronchial wall thickening or exacerbation frequency. Conclusion Specific antibody deficiency is commonly seen in patients with asthma and fungal disease. Vaccination can provide protection and should be considered in this patient group. We need further analysis with a larger cohort of patients to study the association between antibody deficiency, lung function, radiological changes and disease progression.

We evaluated a multiplexed bead-based assay (xMAP® Pneumococcal Immunity assay from Luminex) for the simultaneous determination of antibodies against 14 capsular polysaccharides. Post-vaccination (Pneumovax®) antibody concentrations were measured in 35 healthy children, 40 healthy adults, 99 consecutive patients with increased susceptibility to respiratory infection, and 24 patients with a deficient anti-polysaccharide antibody response. The serotype-specific lower 5th percentile (cutoff) value for the post-immunization antibody concentration was determined in healthy individuals. Eleven of 99 patients (11%) failed to mount a response that was > 5th percentile of controls for at least 6 of the 14 serotypes tested, whereas only 3 of 75 controls (4%) failed to do so. All patients with known anti-polysaccharide antibody deficiency failed to mount a response that was > 5th percentile of controls for at least 6 of the 14 serotypes tested. The XMAP® pneumococcal immunity panel appears useful for identifying individuals with a low response to the unconjugated pneumococcal vaccine.

Summary Specific antibody deficiency (SAD) is an immune deficiency which has been reported in adults and children with recurrent respiratory tract infections; however, the clinical features of SAD are not well described. This study evaluated formally the clinical syndrome of SAD, by comparing the clinical features of children with SAD and those of children with recurrent infection but normal immune function tests. SAD was defined as an adequate IgG antibody response to less than 50% of 12 pneumococcal serotypes tested following 23-valent unconjugated pneumococcal immunization. An adequate IgG antibody response was defined as a post-immunization titre of ≥ 1·3 µg/ml or ≥ four times the preimmunization value. Seventy-four children with recurrent infection were evaluated where immune deficiencies other than SAD had been excluded. Eleven (14·9%) of these children had SAD. Clinical features differed between the group with SAD and the group with normal antibody responses. A history of otitis media, particularly in association with chronic otorrhoea was associated with SAD [relative risk (RR) of SAD in those with chronic otorrhoea 4·64 (P = 0·02)]. SAD was associated with allergic disease, particularly allergic rhinitis [RR of SAD in those with allergic rhinitis 3·77 (P = 0·04)]. These two clinical associations of SAD were independent in this study [RR of chronic otorrhoea in those with allergic rhinitis 0·85 (P = 0·28)]. SAD was not an age-related phenomenon in this population. SAD has a distinct clinical phenotype, presenting as recurrent infection associated with chronic otorrhoea and/or allergic disease, and the condition should be sought in children with these features.