IgG2 Deficiency Research Articles

Hypersensitivity Reaction to Ursodiol Resulting in Cardiac Arrhythmia

Ursodiol (Ursodeoxycholic acid) is a naturally occurring hydrophillic bile acid derived from cholesterol. It is found in small quantities in human bile and in larger quantities in certain species of bear. It has utility in the treatment of both acute and chronic liver disease through multiple mechanisms. We present a case of a hypersensivity reaction to ursodiol resulting in cardiac arrhythmia. A 29 year old male with a past medical history significant for Kugelberg Welander Syndrome, IGG deficiency, and autonomic dysfunction, who was receiving treatment for pseudomonas pneumonia was found to have elevated liver transaminases (alkaline phosphatase 338 IU/L, AST 104 IU/L, ALT 78 IU/L) likely secondary to cholestasis versus drug induced. After excluding other causes of elevated liver function tests, patient was started on ursodiol. Prior to initiation of ursodiol, the patient was in sinus rhythm with vitals significant for temperature of 101.4 deg F and heart rate of 117 beats per minute. Basic metabolic panel was unremarkable. Shortly after the administration of one dose of ursodiol, the patient converted into atrial fibrillation with rapid ventricular response as shown in Figure 1. Physical exam revealed angioedema of the face and upper extremitites as shown in Figures 2 and 3. The patient was given Benadryl and started on a cardizem drip. He returned to sinus rhythm and normal rate within one hour of the initiation of the cardiazem drip, with complete resolution of the angioedema over several days.Figure 1Figure 2Figure 3Ursodiol is a hydrophilic naturally occurring bile acid that is used in the treatment of various liver diseases including primary billary cirrhosis, primary sclerosing cholangitis, hepatitis, cirrhosis, and liver transplant rejection. Multiple mechanisms of action exist for ursodiol including decreasing the toxic endogenous hydrophobic bile acids by a dilutional affect with an increase in the amount of hydrophilic bile acid in cholestatic liver disease. In addition, ursodiol provides cytoprotection of injured bile duct epithelial cells and immunomodulatory effects. Most common side effects of ursodiol include abdominal pain, nausea, itching and diarrhea. In review of literature, there are no documented case reports of a hypersensitivity reaction to ursodiol resulting in cardiac arrhythmia.

Immunoglobulin deficiency in patients with chronic rhinosinusitis: Systematic review of the literature and meta-analysis

Several studies have shown a high prevalence of immunoglobulin deficiencies in patients with chronic rhinosinusitis (CRS). We sought to perform a systematic review and meta-analysis to estimate this prevalence more precisely and to identify patients who need substitution treatment. All case series published after 1990 describing patients with CRS, which was defined as symptomatic rhinosinusitis for more than 12 weeks and documented immunoglobulin deficiencies (including deficiencies of IgG with subclasses, IgA, and IgM; specific antibody deficiencies; and potential common variable immunodeficiency), were retrieved. A meta-analysis of the proportion of any combination of common variable immunodeficiency, IgG deficiency, IgA deficiency, and IgM deficiency in patients with CRS was performed by using logit transformation of the prevalence. Recurrent CRS was defined as rhinosinusitis not controlled by appropriate conservative management for 4 months, and difficult-to-treat CRS was defined as noncontrollable rhinosinusitis despite successful sinus surgery and appropriate conservative management for at least 1 year. The meta-analysis revealed a prevalence of pooled IgG, IgA, and IgM deficiencies in 13% of patients with recurrent CRS and 23% of patients with difficult-to-treat CRS. The prevalence of IgG subclass deficiency (5% to 50%) and specific antibody deficiency (8% to 34%) was increased in patients with CRS, as was the prevalence of respiratory allergies in patients with recurrent CRS (31% to 72%). Immunoglobulin deficiency is a frequent condition in patients with CRS. An even higher prevalence of atopy was observed in patients with recurrent CRS. Therefore immunoglobulin titers and accurate allergy diagnostic workups are strongly recommended in these patients to provide specific treatments for symptom alleviation. However, there is a need for larger prospective studies addressing the effect of specific therapeutic interventions for CRS.

Unusual Cause of Severe Back Pain in a Patient with Isolated IgG Deficiency (P5.113)

Unusual Cause of Severe Back Pain in a Patient with Isolated IgG Deficiency (P5.113)

IgG1 deficiency exacerbates experimental autoimmune myasthenia gravis in BALB/c mice.

Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to neuromuscular junction (NMJ) damage by anti-acetylcholine receptor (AChR) auto-antibodies and complement. In experimental autoimmune myasthenia gravis (EAMG), which is induced by immunization with Torpedo AChR in CFA, anti-AChR IgG2b and IgG1 are the predominant isotypes in the circulation. Complement activation by isotypes such as IgG2b plays a crucial role in EAMG pathogenesis; this suggested the possibility that IgG1, which does not activate complement through the classical pathway, may suppress EAMG. In this study, we show that AChR-immunized BALB/c mice genetically deficient for IgG1 produce higher levels of complement-activating isotypes of anti-AChR, especially IgG3 and IgG2a, and develop increased IgG3/IgG2a deposits at the NMJ, as compared to wild type (WT) BALB/c mice. Consistent with this, AChR-immunized IgG1(-/-) BALB/c mice lose muscle strength and muscle AChR to a greater extent than AChR-immunized WT mice. These observations demonstrate that IgG1 deficiency leads to increased severity of EAMG associated with an increase in complement activating IgG isotypes. Further studies are needed to dissect the specific role or mechanism of IgG1 in limiting EAMG and that of EAMG exacerbating role of complement activating IgG3 and IgG2a in IgG1 deficiency.

RecurrentC. difficilein a Patient with IgG Deficiency

IgG deficiency can predispose to recurrent pyogenic infections. The association of IgG deficiency with Clostridium difficile infection has been infrequently reported in the literature. We present a case of a middle-age woman with multiple hospitalizations for recurrent C. difficile in a short span of time which prompted consideration of a possible fecal transplant. On evaluation, she was found to have low total IgG, with subclass analysis revealing low IgG1 and IgG3. She was started on monthly infusions of immunoglobulins and one year after her last episode of C. difficile she has not had any recurrence. The role of immunoglobulin infusion in the treatment of recurrent C. difficile is controversial, with some studies revealing no clear evidence of benefit. Our case report suggests that the patients who have underlying IgG deficiency may benefit from immunoglobulin, as this can significantly reduce the incidence of recurrent infections and hence save the healthcare costs.

Recurrence of herpes zoster in a young woman with IgG3 deficiency.

Recurrent herpes zoster occurs at a low frequency among immunocompetent individuals. Particularly in young people, recurrent herpes zoster is known to be rare [1]. As the authors found a case of a young woman with no particular past medical history in whom herpes zoster recurred and IgG subclass deficiency was diagnosed on additional testings, we herein report the case.

Wrist Septic Arthritis Due to <i>Streptococcus pneumoniae</i> Revealing a Selective Immunoglobulin G4 Subclass Deficiciency: A Case Report

The pneumococcal septic arthritis is uncommon in healthy adults. In most cases, it occurs in patients with immune deficiency. Its exceptional location at the wrist can maintain doubt with rheumatic causes which are more frequent. IgG4 deficiency found in this patient was the only cause that could be impugned. We report the case of a young woman of 46 years without any evident cause of immunodeficiency and any particular risk factor, managed for septic arthritis of the wrist due to Streptococcus pneumoniae. This case without any apparent risk factors demonstrates that pneumococcal infection in a more distant articulation of the ENT is still possible. Scan has been a very significant contribution in confirming the positive diagnosis that leads to surgical drainage. The approach of the systematic search for the gateway must be done. In the study of the patient’s immune status, the realization of the protein profile could be interesting and then guide the practitioner in the decision to vaccinate the patient against Streptococcus pneumoniae if he was not. We recommend looking always for a cause of immunodeficiency including primary Ig defiencies even among adult.

Pneumonia in common variable immunodeficiency after change in environment

Background Common Variable Immunodeficiency (CVID) is a Primary Immunodeficiency characterized by an association of IgG deficiency with IgA and/or IgM deficiency, and a decrease in the function of specific antibodies, discarding other causes of hipogamaglobulinemia. The recurrent pneumonia are among the main clinical manifestations of CVID,which appear between 20 and 40 years of age in most cases. The aim of this study was to analyse the possible relationship between environmental changes and the onset of pneumonia in patients with primary CVID.

Low dose Rituximab for Preemptive Management of Thrombotic Thrombocytopenic Purpura ( TTP )

Low dose rituximab has been successful in treating some patients with autoimmune cytopenias. Recently reported data indicate preemptive rituximab may postpone hematologic relapses of TTP in patients with chronic severe ADAMTS13 deficiency.A now 22-year-old woman had multi-relapsing TTP with five episodes over the previous 10 years, three of which were successfully treated with four doses of rituximab 375 mg/m2. The most recent course in 2009 was given preemptively because intense ADAMTS13 monitoring had shown that previous hematologic relapses followed shortly after developing severe ADAMTS13 deficiency. Asymptomatic chronic IgG deficiency less than 300 mg% had followed this most recent rituximab course given in 2009.In 2014, continued intense ADAMTS13 monitering disclosed a new progressive decrease in ADAMTS13 levels from normal to severely deficient levels with a weak inhibitor, but no hematologic or clinical changes. Just two 100 mg rituximab doses have been followed by a progressive rise of ADAMTS13 levels to solidly normal values with significant improvement by day 13 post initiation and normalization by day 34.Low dose rituximab could be a viable alternative for preemptively managing TTP patients with persistently severly low ADAMTS13 levels. DisclosuresOff Label Use: Off label use of rituximab to treat TTP.

Hypermucoviscous Klebsiella syndrome without liver abscess in a patient with immunoglobulin g2 immune deficiency.

Background Hypermucoviscous Klebsiella pneumoniae (HMVKP) emerged as a cause of invasive infections in South-East (SE) Asia. It has become the most common cause of liver abscess in that region, and it is a significant causative organism in endogenous endophthalmitis and meningitis. During the past decade, cases of this uniquely virulent organism have been reported outside of SE Asia, with a propensity to affect individuals of SE Asian descent. Cases have been reported from North America including Canada.Methods We report a case of a patient of Filipino descent living in Canada who presented with recurrent HMVKP bacteremia in the absence of pyogenic liver abscess or other localized metastatic Klebsiella infection.Results Investigations identified an immunoglobulin (Ig)G2 deficiency and low IgM indicating potential common variable immunodeficiency, and administration of intravenous immunoglobulins was associated with prevention of further recurrences.Conclusions To our knowledge, this is the first report of HMVKP associated with predisposing antibody deficiency.

Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1): Chronic mucocutaneous candidiasis accompanied by enamel defects and delayed dental shedding

Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1): Chronic mucocutaneous candidiasis accompanied by enamel defects and delayed dental shedding

Myeloid glycosylation defects lead to a spontaneous common variable immunodeficiency-like condition with associated hemolytic anemia and antilymphocyte autoimmunity.

Common variable immunodeficiency (CVID), the most frequent symptomatic primary immune deficiency in humans, is a heterogeneous group of immunologic disorders estimated to affect 1:10,000-1:50,000. Although a clear disease etiology remains elusive, a common characteristic of CVID is deficient IgG Ab production in response to infection or vaccination. Patients often also exhibit autoimmune cytopenias with symptoms of abnormal T cell function, including reductions in naive T cells, which correlate with clinical severity. In this study, we discovered that targeted alterations in the glycome of the myeloid lineage lead to spontaneous immunodeficiency characteristic of both humoral and T cell dysfunction regularly found in human CVID. Mice carrying a myeloid-specific knockout of the Mgat2 gene encoding UDP-GlcNAc:α-6-d-mannoside β-1,2-N-acetylglucosaminyltransferase II enzyme exhibit deficiencies in IgG responses to both protein and polysaccharide conjugate vaccines. Interestingly, the immunodeficiency is associated with decreased T cell activity because of a persistent autoimmune-mediated depletion of naive T cells, which is induced by changes in erythrocyte surface glycosylation. The N-glycosylation dependent autoepitopes that emerge on erythrocytes lead to autoimmune hemolytic anemia, and the causative auto-IgM cross-reacts with naive T cells despite the lack of glycan change on T cells. These findings demonstrate that alterations in erythrocyte glycosylation trigger the development of autoantibodies directed at both erythrocytes and naive T cells, revealing a possible mechanistic link between the induction of autoimmune hemolytic anemia, the reduction in naive T cells, and poor Ab responses to vaccine in severe CVID patients.

AB0359 Deficiencies of Igg and Its Subclasses in Patients Suffering from Rheumatoid Arthritis

BackgroundThe occurrence and clinical significance of IgG subclass deficiencies in rheumatoid arthritis (RA) has only been determined in small investigations (1, 2) and with different methods as the results are...

Targeted modification of complex N-glycosylation results in a spontaneous CVID-like immunodeficiency with anti-lymphocyte autoimmunity (BA14P.204)

Abstract Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency affecting humans. Although a clear disease etiology remains elusive, a common characteristic of CVID is deficient IgG antibody production to infection or vaccination. Many patients also exhibit symptoms of abnormal T cell function, including an apparent lack of naïve T cells which correlates with clinical severity. We describe here one of the first animal models of spontaneous CVID that incorporates aspects of both humoral and T cell dysfunction. The CVID mice exhibit characteristic deficiencies in IgG responses to both protein and polysaccharide vaccines. Interestingly, the immunodeficiency is associated with decreased T cell activity due to a persistent autoimmune response depleting naïve T cells, which appears to be mechanistically linked to changes in erythrocyte surface N-glycosylation. The N-glycosylation dependent auto-epitopes that emerge on erythrocytes were found to cross-react with naïve T cells independent of changes to the latter’s glycosylation profile. While the use of Ig replacement therapy and antibiotics has reduced the number of infections in CVID, the major inflammatory complications such as lung disease, cancer, and autoimmunity still develop; thus our findings provide potential insight into human CVID beyond hypogammaglobulinemia by addressing the mechanisms that may contribute to the more broad defects in adaptive immunity linked to clinical severity.

Isolated Immunoglobulin G4 Subclass Deficiency in a Child with Bronchiectasis

Immunoglobulin G4 subclass deficiency is the most common IgG subclass deficiency, followed by immunoglobulin G2 deficiency. However, IgG2 deficiency is the most common IgG subclass deficiency associated with recurrent infections. Immunoglobulin G4 subclass deficiency occurs in association with other isotype deficiencies. Isolated IgG4 deficiency, however, is much less common. Although respiratory tract infections are the most common manifestation in isolated IgG4 deficiency, other mucosal surfaces may also be affected in IgG4 deficiency leading to diarrhea and recurrent giardiasis. The authors herein report a case of isolated immunoglobulin G4 subclass deficiency in a young girl presenting with bronchiectasis. The diagnosis was established after ruling out other causes of secondary and primary immunodeficiency.

High pneumococcal serotype specific IgG, IgG1 and IgG2 levels in serum and the middle ear of children with recurrent acute otitis media receiving ventilation tubes

Recurrent acute otitis media (AOM), frequently caused by Streptococcus pneumoniae, is a major paediatric health problem. A reduced antibody response against pneumococcal polysaccharides may contribute to an increased susceptibility to AOM. Using a multiplex bead-based assay we measured IgG, IgG1 and IgG2 levels against 11 pneumococcal polysaccharides in serum samples from 166 children below 3 years of age with a history of at least 3 episodes of acute otitis media receiving ventilation tubes, and 61 healthy controls. Pneumococcal serotype specific IgG was also determined in 144 middle ear effusion samples. Pneumococcal serotype specific IgG, IgG1 and IgG2 levels were similar in children with or without AOM, except for IgG and IgG1 levels against serotype 5, which were significantly higher in children with a history of frequent AOM (IgG: 137.5μg/ml vs. 84.0μg/ml; p=0.02; IgG1: 24.5μg/ml vs. 18.2μg/ml; p=0.05). The age-related development of pneumococcal serotype-specific IgG, IgG1 and IgG2 levels was similar in children with or without a history of AOM. Pneumococcal serotype specific IgG was present in middle ear effusion and these levels correlated significantly with serum titres. Children with a history of frequent AOM receiving ventilation tubes do not have a deficient IgG, IgG1 or IgG2 response against pneumococcal polysaccharides, either induced by vaccination or due to natural exposure. The strong correlation between IgG levels in serum and the middle ear suggests parenteral pneumococcal conjugate vaccination induces antibodies in the middle ear which may therefore contribute to reducing the burden of AOM.

Kartagener's syndrome with immunoglobulin G subclass deficiency

Kartagener syndrome is characterized by the triad of situs inversus, bronchiectasis, and chronic paranasal sinusitis. Recurrent sinopulmonary infection, the major determinant for diagnosing immunodeficiency, is the most common clinical manifestation of the disease. A 17-year-old female patient presented with dyspnea, cough, sputum, nasal congestion, and rhinorrhea for more than 5 years. Nasal symptoms and dyspnea had not been controlled by intermittent treatment with mucolytics and antibiotics from primary clinics since 3 months before visiting our clinic. Chest X-ray and computed tomography showed situs inversus, dextrocardia and bronchiectasis. Paranasal sinus series revealed mucosal thickening and haziness on both maxillary sinus. Serum immunoglobulin (Ig) G4 was decreased, but total IgG was within normal range. Under the diagnosis of Kartagener syndrome with IgG4 deficiency, monthly intravenous IgG (IVIG) treatment was performed for 6 months. Her symptoms were well controlled and the frequency of antibiotics use was markedly decreased. We report a patient having the Kartagener syndrome with IgG4 deficiency that was successfully controlled with a 6-month-treatment of IVIG. (Allergy Asthma Respir Dis 2013;1:288-291)

Antibody response to pneumococcal vaccination in children with chronic or recurrent rhinosinusitis

PurposeAlthough chronic and recurrent rhinosinusitis is prevalent in children, little is known about its causes. Here, we investigated the humoral immunity in children with chronic or recurrent rhinosinusitis.MethodsWe examined 16 children attending the outpatient clinic at the CHA Bundang Medical Center including 11 boys and 5 girls, aged 3.11 years (mean age, 5.6 years), who had rhinosinusitis for >3 months or >3 times per year. The complete blood count with differential and total serum concentrations of Immunoglobulin (Ig) E, IgA, IgD, IgM, IgG, and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) of all children were measured. All subjects received 23-polysaccharide pneumococcal vaccination (PPV), and the levels of antibodies to 5 serologic types (4, 6B, 14, 18C, and 23F) of pneumococcal capsular polysaccharide antigens were measured before and after vaccination. Post-PPV antibody titers ≥0.35 µg/mL or with a ≥4-fold increase were considered as positive responses.ResultsThe titers of IgG, IgA, IgD, and IgM were within normal range in all 16 children, whereas the total IgE concentration was higher than normal in 2 children. IgG1 deficiency was observed in 1 patient and IgG3 deficiency in 3. After PPV, 1 patient failed to respond to all 5 serologic types, 2 failed to respond to 4 serologic types, and 2 failed to respond to 3 serologic types.ConclusionClinicians should consider the evaluation of humoral immune functions in children with chronic or recurrent rhinosinusitis who do not respond to prolonged antibiotic treatment.

Serum immunoglobulin levels in children with respiratory infections who used a synbiotic dietary supplement

Objective. The purpose of this study was to investigate the effectiveness and the optimal time of supplementation with synbiotic in atopic children with common respiratory and/or ear infections. Methods. We recruited inpatients children with frequent respiratory infections and/or inflammation of the ear and analyzed pretreatment and post-treatment level of immunoglobulins using repeated measures analysis. Results. Hospitalized children are old averaging 19 months, all had deficiency of IgA, 58% showed deficiency of IgG, 81% are the atopics and at the same time, suffer from respiratory infection (pneumonia 45%, middle ear infection 26%, pharyngitis 74%) and concomitant diseases (anemia 26%, enlarge adenoids 6%, eczema13%, wheezing bronchitis16%, asthma 42%, urticaria 3%). After 3 months treatment by synbiotic level of IgA increased for 1.8 times up from 0.33±3.42 g/l to 0.6±0.78 in 35% children and after 6 months increased for 3.9 times up to 1.3±1.76 in 81% children (t=0,43, p<0,05). Conclusion. Optimal duration of supplementation with synbiotic to reduce the risk of common infectious disease, in young, atopic children, is at least 6 months although achieved clinical improvement after 3 months.

IgG3 deficiency and severity of 2009 pandemic H1N1 influenza

The severity of the 2009 pandemic H1N1 influenza (H1N1 pdm 09) in immune deficient children is unknown. The aim of the present study was to investigate this in a case of complete IgG3 deficiency complicated by pneumonia and asthma attack. The clinical parameters of the IgG3 deficiency patient were compared with those of four control patients using 95% confidence intervals. These control patients were selected from 71 patients admitted due to pneumonia or bronchitis caused by H1N1 pdm 09, and were chosen according to age, absence of pretreatment with oseltamivir before admission, presence of a past history of asthma, use of antibiotics, and combination of inhalation of a beta2 agonist and treatment with i.v. methylprednisolone for asthma attack. The IgG3 deficiency patient had significantly longer duration of admission and period of oseltamivir, with a significantly decreased pulse oxygen saturation and increased maximum serum C-reactive protein, creatine kinase and urinary excretion of β2-microglobulin/creatinine, compared with the controls (P < 0.05). Complete IgG3 deficiency is possibly associated with severity of the clinical course of pneumonia and asthma attack in children suffering from H1N1 pdm 09.