Antibody Deficiency Disorders Research Articles

Interstitial lung diseases in inborn errors of immunity.

Our goal is to review current understanding of interstitial lung disease (ILD) affecting patients with inborn errors of immunity (IEI). This includes understanding how IEI might predispose to and promote development or progression of ILD as well as how our growing understanding of IEI can help shape treatment of ILD in these patients. Additionally, by examining current knowledge of ILD in IEI, we hope to identify key knowledge gaps that can become focus of future investigative efforts. Recent identification of novel IEI associated with ILD and the latest reports examining treatment of ILD in IEI are included. Of noted interest, are recent clinical studies of immunomodulatory therapy for ILD in common variable immunodeficiency. ILD is a frequent complication found in many IEI. This article provides a guide to identifying manifestations of ILD in IEI. We review a broad spectrum of IEI that develop ILD, including antibody deficiency and immune dysregulation disorders that promote autoimmunity and autoinflammation. This work integrates clinical information with molecular mechanisms of disease and diagnostic assessments to provide an expedient overview of a clinically relevant and expanding topic.

Predominant Antibody Deficiency and Risk of Microscopic Colitis: a Nationwide Case–Control Study in Sweden

Purpose Predominant antibody deficiency (PAD) disorders, including common variable immunodeficiency (CVID), have been linked to increased risk of gastrointestinal infections and inflammatory bowel diseases. However, there are limited data on the relationship between PAD, specifically CVID, and risk of microscopic colitis (MC).MethodsWe performed a nationwide case–control study of Swedish adults with MC diagnosed between 1997 and 2017 (n = 13,651). Data on biopsy-verified MC were retrieved from all of Sweden’s pathology departments through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) study. We defined predominant antibody deficiency using International Union of Immunologic Societies (IUIS) phenotypic classification. Individuals with MC were matched to population controls by age, sex, calendar year, and county. We used logistic regression to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).ResultsThe prevalence of PAD in MC was 0.4% as compared to 0.05% in controls. After adjustment for potential confounders, this corresponded to an aOR of 7.29 (95%CI 4.64–11.63). The magnitude of the association was higher for CVID (aOR 21.01, 95% 5.48–137.44) compared to other antibody deficiencies (aOR 6.16, 95% CI 3.79–10.14). In exploratory analyses, the association between PAD and MC was particularly strong among males (aOR 31.73, 95% CI 10.82–135.04).ConclusionIn this population-based study, predominant antibody deficiency was associated with increased risk of MC, particularly among males. Clinicians who encounter these patients should consider a detailed infectious history and screening for antibody deficiency.

Predominant Antibody Deficiency and Risk of Microscopic Colitis: A Nationwide Case-Control Study in Sweden

ObjectivePredominant antibody deficiency (PAD) disorders, including common variable immunodeficiency (CVID), have been linked to increased risk of gastrointestinal infections and inflammatory bowel diseases. However, there are limited data on the relationship between predominant antibody deficiency disorders, specifically CVID, and the risk of microscopic colitis (MC). DesignWe performed a nationwide case-control study of Swedish adults with MC diagnosed between 1997 and 2017 (n = 13,651). Data on biopsyverified MC were retrieved from Sweden's all 28-pathology departments through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) study. We defined predominant antibody deficiency using International Union of Immunologic Societies (IUIS) phenotypic classification. Individuals with MC were matched to population controls by age, sex, calendar year, and county. We used logistic regression to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). ResultsThe prevalence of PAD in MC was 0.4% as compared to 0.05% in controls. After adjustment for potential confounders, this corresponded to an aOR of 7.29 (95%CI 4.64–11.63). The association was higher for CVID (aOR 21.01, 95% 5.48–137.44) compared to other antibody deficiencies (aOR 6.16, 95% CI 3.79–10.14). In exploratory analyses, the association between PAD and MC was particularly strong among males (aOR 31.73, 95% CI 10.82–135.04). ConclusionIn this population-based study, predominant antibody deficiency was associated with risk of MC, particularly among males. Clinicians who encounter these patients should consider a detailed infectious history and screening for antibody deficiency.

Specific Cellular and Humoral Immune Responses to the Neoantigen RBD of SARS-CoV-2 in Patients with Primary and Secondary Immunodeficiency and Healthy Donors

Patients with antibody deficiency disorders, such as primary immunodeficiency (PID) or secondary immunodeficiency (SID) to B-cell lymphoproliferative disorder (B-CLPD), are two groups vulnerable to developing the severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). The data on adaptive immune responses against SARS-CoV-2 are well described in healthy donors, but still limited in patients with antibody deficiency of a different cause. Herein, we analyzed spike-specific IFN-γ and anti-spike IgG antibody responses at 3 to 6 months after exposure to SARS-CoV-2 derived from vaccination and/or infection in two cohorts of immunodeficient patients (PID vs. SID) compared to healthy controls (HCs). Pre-vaccine anti-SARS-CoV-2 cellular responses before vaccine administration were measured in 10 PID patients. Baseline cellular responses were detectable in 4 out of 10 PID patients who had COVID-19 prior to vaccination, perceiving an increase in cellular responses after two-dose vaccination (p < 0.001). Adequate specific cellular responses were observed in 18 out of 20 (90%) PID patients, in 14 out of 20 (70%) SID patients and in 74 out of 81 (96%) HCs after vaccination (and natural infection in some cases). Specific IFN-γ response was significantly higher in HC with respect to PID (1908.5 mUI/mL vs. 1694.1 mUI/mL; p = 0.005). Whereas all SID and HC patients mounted a specific humoral immune response, only 80% of PID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC patients (p = 0.040), without significant differences between PID and HC patients (p = 0.123) and between PID and SID patients (p =0.683). High proportions of PID and SID patients showed adequate specific cellular responses to receptor binding domain (RBD) neoantigen, with a divergence between the two arms of the adaptive immune response in PID and SID patients. We also focused on the correlation of protection of positive SARS-CoV-2 cellular response to omicron exposure: 27 out of 81 (33.3%) HCs referred COVID-19 detected by PCR or antigen test, 24 with a mild course, 1 with moderate symptoms and the remaining 2 with bilateral pneumonia that were treated in an outpatient basis. Our results might support the relevance of these immunological studies to determine the correlation of protection with severe disease and for deciding the need for additional boosters on a personalized basis. Follow-up studies are required to evaluate the duration and variability in the immune response to COVID-19 vaccination or infection.

Correlation between Clinical and Immunological Variables and Humoral Response to SARS-CoV-2 Vaccination in Adult Patients with Antibody Deficiency Disorders.

Prophylactic vaccination has proven to be the most effective strategy to fight the COVID-19 pandemic. This was a prospective observational cohort study involving 30 predominantly antibody deficiency disorders (ADD)-afflicted adult patients on immunoglobulin replacement therapy vaccinated with three doses of the mRNA-1273 COVID-19 vaccine, and 10 healthy controls. Anti-RBD IgG antibodies were determined in plasma samples collected just before the first dose of mRNA-based COVID-19 vaccine and on weeks 4, 8, 24, and 28 following the first vaccination. Patients were categorized based on the levels of anti-RBD antibodies determined on w8 as non-, low-, and responders. Chi-square and Kruskal-Wallis tests were used to see if any variables correlated with humoral response levels. Any adverse effects of the mRNA-based vaccine were also noted. The COVID-19 vaccine was safe and well-tolerated. The humoral response elicited at w8 after vaccination depended on the type of ADD, the type of immunoglobulin deficiency, the presence of granulomatous lymphocytic interstitial lung disease, recent use of immunosuppressive drugs, and the switched memory B cells counts. The third vaccine dose boosted humoral response in previous responders to second dose but seldom in non-responders. The humoral response of patients with predominant ADD depends mostly on the type of immunodeficiency and on the frequency of B and T cell populations.

Reconstitution of IgG Subclasses Following Immunoglobulin Administration in Adult Patients with Common Variable Immune Deficiency

Background: Immunoglobulin (Ig) therapy reduces the frequency and severity of infection among patients with antibody deficiency disorders. However, a subset of patients lacks adequate clinical response. Objective: The purpose of this study was to determine in adult common variable immune deficiency (CVID) patients (A) if lack of clinical response to Ig therapy correlates with lack of reconstitution of IgG subclass (es), (B) correlation between Ig dosing and/or IgG trough levels and IgG subclass reconstitution, (C) and most common impaired Streptococcus pneumoniae (S. pneumoniae) serotype antibody response. Methods: Single-institution, retrospective chart review for CVID patients at immunology clinics from 2015 to 2019. Patients were monitored every 3–6 months for IgG dosage, IgG trough levels, IgG subclass reconstitution, infectious episodes (chronic sinusitis, bronchitis, upper respiratory, and lower respiratory tract infections), urinary tract infections, and antibiotic use. Follow-up was calculated in patient years. Results: Twenty-five of 41 patients achieved complete reconstitution of all IgG subclasses, and 16/41 demonstrated intermittent or lack of reconstitution. There were significantly less (p < 0.001) infections among fully reconstituted patients (0.66 ± 0.19 infections per patient year) as compared to those with intermittent or lack of reconstitution (1.26 ± 0.13 infections per patient year). There was a significant correlation between IgG trough levels and IgG subclass reconstitution. Most common impaired S. pneumoniae serotype included 3, 4, 9n, 10a, 11a, 12f, and 15b. Conclusions: Incomplete IgG subclass reconstitution was associated with increased frequency of infections. IgG trough levels correlate with IgG subclass reconstitution. A limited number of S. pneumoniae serotype antibodies are commonly impaired in CVID.

Achieving equitable management of allergic disorders and primary immunodeficiency in a Black, Asian and Minority Ethnic population

Achieving equitable management of allergic disorders and primary immunodeficiency in a Black, Asian and Minority Ethnic population

Characteristics of a diverse urban population of primary antibody deficiency patients

Primary antibody deficiency (PAD) disorders are most common primary immunodeficiencies, yet much of the research on these disorders is limited to predominantly Caucasian populations at specialized referral centers. We aimed to explore whether there are clinically important differences within a diverse urban population of PAD patients. Retrospective analysis of electronic medical records at Boston Medical Center (BMC) dating back to 2012 was conducted to identify patients with ICD-9/ICD-10 diagnostic codes for agammaglobulinemia, common variable immunodeficiency, hereditary hypogammaglobulinemia, nonfamilial hypogammaglobulinemia, and IgG deficiency. 57 BMC patients were confirmed to have PAD deficiency upon chart review and included in this study with social demographics, clinical histories, and laboratory characteristics recorded. The PAD cohort at BMC is more diverse than that of the United States Immunodeficiency Network (USIDNET), with 15.8% of BMC subjects identifying as Black/African American compared to 2.8% of USIDNET (P < 0.0001) and 12.3% of BMC subjects identifying as Hispanic compared to 3.5% of USIDNET (P = 0.002). IgG replacement therapy was prescribed less commonly in the BMC cohort (37%) compared to USIDNET (87%, P < 0.0001). Bronchiectasis was more common in Black/African American patients (55.6%, P = 0.043) compared to other PAD patients in the BMC cohort. An urban population of PAD patients that is racially and ethnically more diverse than USIDNET had significantly less usage of IgG replacement therapy. Also, bronchiectasis was more common in Black/African American patients. Further work is needed to explore how social disparities may be influencing treatment and outcomes of PAD patients.

Epidemiological and clinical features of patients with primary antibody deficiency disorders in the east of Turkey

Aim: To describe the demographic and clinical features of patients diagnosed with primary antibody deficiency Material and Methods: The medical records of pediatric patients who were diagnosed with primary antibody deficiency were reviewed. Patients were diagnosed with primary antibody deficiency based on the European Society for Immunodeficiencies diagnostic criteria. Result: A total of 60 patients with primary antibody deficiency were identified; 39 patients (65%) were male and median age was 5 (1-18) years of age, while median diagnosis age was 3 (6 mo-14 yr) years. Twenty-one patients (35%) were diagnosed with transient hypogammaglobulinemia of infancy, thirteen (21.7%) with selective Ig A deficiency, five (8.3%) with congenital agammaglobulinemia, five (8.3%) with selective Ig M deficiency, five (8.3%) with unclassified hypogammaglobulinemia, four (6.7%) with Ig G subclass deficiency, two (3.3%) with severe combined immune deficiency, two (3.3%) with common variable immunodeficiency, two (3.3%) with hyper Ig M syndrome, and one patient was diagnosed with pneumococcal vaccine responsiveness, respectively. Eleven patients (18.3%) had consanguinity and six patients (10%) had family history. The most common complaint was frequent respiratory tract infections. Four patients had dermatitis in addition to infection. Three patients had hematopoietic stem cell transplantation and 23 patients (38.3%) received intravenous immunoglobulin treatment. Two patients died during the follow up. Conclusion: Our results indicated that diagnosis is delayed and the patients who are diagnosed with primary antibody deficiency frequently have respiratory tract infections.

Targeted next-generation sequencing for genetic diagnosis of 160 patients with primary immunodeficiency in south China.

Primary immunodeficiency disorders (PID) is a group of heterogeneous diseases mainly characterized by severe and recurrent infections and an increased susceptibility to lymphoproliferative, atopic, and autoimmune conditions. The clinical diagnosis should preferably be complemented by a genetic diagnosis. To date, PID-related reports from China seldom attempt to make a genetic test for their patients. Our study aimed to evaluate demographic data, clinical manifestations, and molecular diagnosis of PID patients from southern China. Moreover, by comparison with previous reports, we provide a picture of the current status of PID in mainland China. A total number of 160 pediatric PID patients (106 males and 54 females) were enrolled, and targeted next-generation sequencing was conducted using 269 PID-related genes and subsequently confirmed by Sanger sequencing and familial segregation analysis. The autoinflammatory disease group was the most common subcategory of PID (20%), followed by immune dysregulation (17.5%) and combined immunodeficiencies (16.2%). Antibody deficiency disorders were identified in only 11.9% of the cohort. The putative causative gene was identified in 70 patients (43.8%), and an X-linked pattern was found in 45.7% of the genetically diagnosed patients. The current study provides the first collective study of PID phenotypes and genotypes in south China and provides a strong argument for the diagnostic application of targeted next-generation sequencing panels in patients with suspected PID.

Gastroduodenal Disorders in Patients with CVID Undergoing Immunoglobulin Therapy.

Common variable immunodeficiency (CVID) encompasses a heterogeneous group of primary antibody deficiency disorders characterized by recurrent infections, autoimmunity and malignancies. Gastrointestinal manifestations are frequently associated with CVID. In this cross-sectional study, we evaluated gastric and duodenal involvement in a cohort of adult patients with CVID. Upper gastrointestinal endoscopy was performed in 58 patients (26 males, mean age 47.8±15.6 years), diagnosed with CVID according to 2014 ESID criteria. Random biopsies were collected from gastric antrum and descending duodenum for the all enrolled subjects. Intraepithelial lymphocytosis in descending duodenum was defined as the presence of 25 lymphocytes per 100 enterocytes. The major histopathological findings that we found were: a) chronic active gastritis (44.8%), Helicobacter pylori-associated (8.6%), b) chronic duodenitis (39.6%) with intraepithelial lymphocytosis (31%) and absence of plasma cells (18.9%) and c) autoimmune atrophic gastritis (5.2%). Three patients (5.2%) presented Intestinal Metaplasia (IM) of the gastric antrum. This finding was associated with H. pylori infection and persisted after the eradication in one patient. IM was associated with autoimmune atrophic gastritis in two cases. Giardia lamblia infection was observed in the duodenum samples from three patients (5.2%). A diagnosis of Gastric adenocarcinoma was made in a 58-year- old woman diagnosed with gastric dysplasia one year earlier. In our cohort of CVID patients, gastro-duodenal histopathological findings, including malignancies, are frequent and can affect long-term prognosis. A rigorous endoscopic follow-up is needed in CVID patients irrespective of the gastrointestinal symptoms.

Pulmonary Manifestations of Primary Immunodeficiencies in Children - A Review

Primary immunodeficiency diseases (PIDs) are inherited defects of the innate or adaptive arms of the immune system that differs from secondary immunodeficiencies. Respiratory disorders are significant causes of morbidity and the leading causes of death (30% -65%) in both children and adults with PIDs. The spectrum of respiratory manifestations is extremely wide due to PIDs. PIDs are broadly classified according to the components of the immune system that is primarily disrupted. Predominant antibody deficiency disorders are the most frequent and comprise approximately 70-75% of all PIDs. The most common clinical manifestations are infections involving the respiratory tract e.g. rhinosinusitis, otitis media, bronchitis, bronchiectasis and recurrent pneumonia (30% -65%). Recurrent respiratory infections are often the first warning sign. Timely diagnosis and appropriate therapy can improve or at least decelerate the progression of these complications. Infectious and non-infectious respiratory complications determinate the patient’s prognosis. These complications are associated with significant morbidity and mortality in PID patients. Appropriate awareness of these manifestations is essential, especially for the pulmonologist to reduce morbidity and mortality in PID patients.Bangladesh J Child Health 2018; VOL 42 (2) :86-93

Delayed Diagnosis and Complications of Predominantly Antibody Deficiencies in a Cohort of Australian Adults.

Predominantly antibody deficiencies (PADs) are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy. To characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia. We identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features. 179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7 years (range: 16-87 years), of whom 98 (54.7%) were female. The majority of patients (116; 64.8%) met diagnostic criteria for common variable immunodeficiency (CVID), and 21 (11.7%) were diagnosed with X-linked agammaglobulinemia (XLA). Unclassified hypogammaglobulinemia (HGG) was described in 22 patients (12.3%), IgG subclass deficiency (IGSCD) in 12 (6.7%), and specific antibody deficiency (SpAD) in 4 individuals (2.2%). The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency). There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1 year. The median age of reported symptom onset was 20 years for those with a diagnosis of CVID, with a median age at diagnosis of 35 years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the cohort. Our data are largely consistent with the experience of other centers internationally, with clear areas for improvement, including reducing diagnostic delay for patients with PADs. It is likely that these challenges will be in part overcome by continued advances in implementation of genomic sequencing for diagnosis of PADs, and with that opportunities for targeted treatment of non-infectious complications.

In vitro chromosomal radiosensitivity in patients with common variable immunodeficiency

Common variable immunodeficiency (CVID) is one of the predominant antibody deficiency disorders, some evidence of which indicates that chromosome instability is present in these patients. An increased risk of cancer in patients with CVID has been documented. This study was undertaken to highlight radiation sensitivity in CVID patients and to clarify the genetic basis of this defect in these cases. Stimulated lymphocytes of the studied subjects were exposed to low-dose gamma-rays in the G2 phase or the G0 phase of the cell cycle and chromosomal aberrations were scored. Lymphocytes of healthy individuals, ataxia telangiectasia (AT) cases and a group of acute lymphoblastic leukemia (ALL) patients were investigated in the same way as controls. By two methods of analysis (one-way ANOVA and unpaired t-test), the CVID cases were significantly more radiosensitive than healthy controls based on the results of the G2 and the G0 assays. First-degree relatives of CVID patients were radiosensitive by the micronucleus assay which showed a significant difference as compared with normal controls (p = 0.001). In conclusion, this study may support that chromosomal radiosensitivity in CVID patients is a marker of genetic predisposition to the disease. The results might be a clue to describe the increased risk of cancer in CVID patients.

Systematic investigation for underlying causes of recurrent infections in children: surveillance of primary immunodeficiency.

Recurrent infections seem to be a common complaint in children who are referred to general practitioners and pediatricians offices. Detection of primary immunodeficiencies (PID) etiology is very important for achieving appropriate diagnosis and treatment of these patients. The absence of appropriate treatment could lead to subsequent complications, in a hospital inpatient and/or outpatient settings. This study was performed in a group of children with recurrent infections to identify patients with underlying PID. A cross-sectional study was designed to evaluate the final clinical diagnosis obtained in 100 pediatric patients with a history of recurrent infections referred to Children s Medical Center, Tehran, Iran, during one year (2011-2012). History taking and physical examination, complementary laboratory tests including immunological investigations were done to confirm the main causes of disease according to our previously published stepwise approach to recurrent infections. Among all studied patients, 21% (11 males and 10 females) were diagnosed to have PID. Parental consanguinity (p = 0.001) and soft tissue infections (p = 0.004) were significantly higher in PID group, comparing to other causes of recurrent infections. Gender and location of infections were also linked to the type of PID including antibody deficiency, combined immunodeficiency and phagocytosis disorders. The real rate of PID as a cause of recurrent infection appears to be much higher than what is generally considered in a se-lected group of pediatric patients; so, following the suggested stepwise guideline can im-prove timely diagnosis and appropriate treatment of these patients.

Increased Incidence of Fatigue in Patients with Primary Immunodeficiency Disorders: Prevalence and Associations Within the US Immunodeficiency Network Registry.

Patients with primary immunodeficiency (PID) often report fatigue, yet this symptom has not been studied in PID. Fatigue affects 6-7.5% of healthy adults. The goal of this study is to estimate the prevalence of fatigue in patients with PID and investigate its associated factors. We analyzed 2537 PID patients registered in USIDNET to determine responses to the field "fatigue" in the core registry form. Demographics, immune phenotypes, and comorbid conditions were compared between fatigued and non-fatigued patients to identify relevant associations and potential drivers. A focused analysis was performed for patients with predominantly antibody deficiency disorders (PADs). Fatigue was reported in 25.9% (95% CI 23.7-28.3) of PAD patients, compared to 6.4% (95% CI 4.9-8.2) of non-PAD. Patients with common variable immunodeficiency (CVID) had the highest prevalence of fatigue (p<0.001) among all PID diagnoses. Other factors that were associated with a higher rate of fatigue among PAD patients included female sex, higher BMI, depression, bronchiectasis, and autoimmunity. Additionally, fatigued PAD patients had lower absolute lymphocyte, CD3, CD4, and CD8 counts compared to non-fatigued patients. Our findings suggest that fatigue is overrepresented in PAD patients. Prospective studies to estimate prevalence, risk factors, and fatigue etiology in PID are warranted, so therapeutic interventions can be considered.

7(th) International Immunoglobulin Conference: Poster presentations.

Immunoglobulin (Ig) therapy is the mainstay of treatment for primary antibody deficiency disorders and has proved to be efficacious in specific autoimmune and inflammatory diseases. Additionally, due to the role of Ig in complement activation, it is being used increasingly in solid organ transplantation. Furthermore, Ig is the primary or secondary treatment in some immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN). This session discusses trends of Ig use in Europe, proposed mechanisms of action, adverse effects and the potential role of Ig therapy in transplantation. Dr Šedivá reported that Ig therapy is available in all European countries, although dosing is not always optimal, due partly to reimbursement plans. Subcutaneous immunoglobulin (SCIg) has become increasingly accessible in recent years; however, the chosen route of administration still varies widely between countries. Dr Berger's presentation on optimization of Ig therapy in neuropathies, and Dr Rojavin's report on a pharmacometric model to determine the serum IgG levels achieved by different dosing regimens in primary antibody deficiency (PAD) patients, led to the challenging concept of using individualized dosing strategies. Dr Klehmet reported on the potential benefit of using antigen-specific T cell responses as a biomarker of IVIg responsiveness in CIDP patients, while Dr von Gunten provided an insight into the mechanisms of action of Ig preparations, suggesting that the immunoregulatory effects of IgG may be mediated by IgG antibodies against glycans. Dr Basta reported on the potential thrombogenic adverse effects associated with Ig therapy. Although these adverse events are rare, further studies are needed to clarify the relationship between Ig replacement and immunomodulatory therapy and these adverse reactions. In transplantation, Dr Carbone described that prophylactic IVIg treatment was found to decrease the incidence of severe infection in IgG hypogammaglobulinaemia patients undergoing heart transplantations. Furthermore, Dr Clatworthy reported that inactivating polymorphisms in the inhibitory receptor FcγRIIB do not impact upon kidney allograft survival.

Quality of life in children with primary antibody deficiency.

Primary antibody deficiency disorders (PADs) can have an excellent outlook if diagnosed early and treated appropriately, but require lifelong treatment with immunoglobulin replacement. Some carry risks of inflammatory complications even with optimal treatment. Quality of life (QoL) and the psychological impact of PADs has been relatively little studied, particularly in children. The purpose of this study was to evaluate QoL and psychological impact in a large group of children affected by a range of PADs, as well as a group with transient hypogammaglobulinemia of infancy (THI). Both parental and, where appropriate, child ratings, were collected using standardised questionnaires (PedsQL and SDQ). Higher rates of psychological difficulties, particularly emotional and peer-relationship difficulties were found in children with PAD when compared with healthy controls. Quality of life was poorer than in healthy controls, and also worse than in children affected by diabetes mellitus. Variations in QoL and the degree of psychological difficulties were found between specific diagnostic groups, with children affected by THI being amongst those with the lowest scores for QoL. Further studies are needed to corroborate and extend these findings, but this study confirms previous findings that primary antibody deficiency has a significant impact on quality of life and psychological well-being, and additionally suggests that the impact varies according to severity of the underlying condition. For those with significant difficulties psychological intervention at an early stage may be beneficial.Electronic supplementary materialThe online version of this article (doi:10.1007/s10875-014-0072-x) contains supplementary material, which is available to authorized users.

Intravenous Immunoglobulın Therapy in Dermatology: An Update

Intravenous immunoglobulin (IVIG) is a fractioned blood product consisting of IgG antibodies which was first used in antibody deficiency disorders. It is increasingly being used for several inflammatory and autoimmune conditions. IVIG can also be used in a wide range of dermatological diseases which are difficult to treat including autoimmune bullous skin diseases and toxic epidermal necrolysis. The use of IVIG in dermatological disorders is discussed in this article.

Isolation of poliovirus shedding following vaccination in children with antibody deficiency disorders

Prolonged excretion of oral poliovirus may occur in primary antibody deficiency states. Those patients who persistently excrete the virus may pose the risk of aiding viral propagation in the environment. This study therefore aimed to identify the potential for prolonged poliovirus shedding by patients diagnosed with congenital antibody deficiency disorders. A cohort of children later diagnosed with antibody deficiency disorders was included in the study. Patient history was taken for each participant, with emphasis on vaccination data. Laboratory investigations included immunoglobulin profiles and stool sample collection at one month intervals from each patient, with follow-up for six months. The virus isolates were detected using enzyme-linked immunosorbent assay (ELISA) and molecular reverse transcription polymerase chain reaction (RT-PCR) techniques. On the initial sample screens, one patient revealed excretion one for Sabin-like strain 1 (SL1) and one patient revealed excretion for Sabin like strain 2 (SL2). Only one patient continued to shed the virus (SL1) on three successive samples and on follow-up. There was no correlation between the level of immunoglobulins and duration of virus shedding. The study demonstrates the low occurrence of prolonged vaccine polioviruses shedding in a group of children exposed to a live vaccine.