Sudden death of a child associated with invasive non-typeable Haemophilus influenzae infection with underlying IgG2 subclass deficiency.

Haemophilus influenzae can be divided into typeable and non-typeable strains. Although non-typeable Haemophilus influenzae (NTHi) is less likely to be a fatal bacterium, invasive NTHi infection has been reported to increase worldwide. This study presents a case of sudden death of a child with invasive NTHi infection and underlying immunoglobulin G2 (IgG2) deficiency. A two years seven months male child with a high fever was found unresponsive in bed, lying face down on a soft pillow. Later, the hospital declared the subject dead. An autopsy revealed that the only noteworthy finding was tissue congestion. The histopathological findings disclosed neutrophils within blood vessels of major organs. Meanwhile, the formation of the micro abscess was not visible, which indicated bacteremia. The bacterial blood culture was positive for Haemophilus Influenzae. Polymerase chain reaction assay revealed the absence of an entire capsule locus. The transmission electron microscopy showed that the colonies did not have polysaccharide capsules. Based on the above findings, the strain was identified as NTHi. Furthermore, the value of serum IgG2 was deficient, indicating the presence of IgG2 subclass deficiency. The subject eventually died from asphyxia by smothering due to a comorbid condition with a high fever brought on by NTHi-induced bacteremia and lying face down. IgG2 subclass deficiency contributed to the development of invasive NTHi infection. The invasive NTHi infection might present a risk of sudden death, particularly for immunocompromised children. As forensic pathologists and pediatricians may encounter such a problematic clinical condition, they should be aware of this.

Serum Protein Electrophoresis May Be Used as a Screening Tool for Antibody Deficiency in Children and Adolescents.

Background: Patients with antibody deficiency may experience exceptionally long diagnostic delays, increasing the risk of life-threatening infections, end-organ damage, mortality, and health costs. Objective: This study aimed to analyze serum protein electrophoresis and verify the correlation between calculated globulin (CG, total protein minus albumin levels) or electrophoretically determined serum gamma globulin fraction (Gamma) with IgG levels in children and adolescents under 18 years old (yo). Methods: We analyzed serum protein electrophoresis (GC or Gamma) and IgG levels from 1215 children and adolescents under 18 yo, classified into 5 age groups. We verified the correlation between CG or Gamma with serum IgG levels. Results: Serum IgG levels varied according to age groups (from 4.3 ± 2.3 g/l in children under 6 months old to 11.4 ± 3.2 g/l in adolescents in the 10-<18 yo group). CG sensitivity and specificity to detect IgG below the reference range for all patients were 93.1% and 81.8%, respectively, and varied according to age group. Gamma sensitivity and specificity for all patients were 100% and 87.8%, respectively, and varied according to age group as well. We found serum IgG levels below the age reference level in 29 patients (2.4% of the cases) using CG or Gamma levels. Conclusion: Both CG and Gamma levels may be of utility as a screening tool for earlier diagnosis of antibody deficiency in children and adolescents under 18 yo.

Association of mannose-binding lectin, ficolin-2 and immunoglobulin concentrations with future exacerbations in patients with chronic obstructive pulmonary disease: secondary analysis of the randomized controlled REDUCE trial.

BACKGROUND: The innate and adaptive immune system is involved in the airway inflammation associated with acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). We evaluated the association of mannose-binding lectin (MBL), immunoglobulin (Ig) and ficolin-2 concentrations with COPD exacerbations and according to the glucocorticoid treatment duration for an index exacerbation. METHODS: Post-hoc analysis of the randomized, double-blind, placebo-controlled REDUCE trial of 5 vs. 14 days of glucocorticoid treatment for an index exacerbation. MBL, ficolin-2 and total IgG/IgA and subclass concentrations were determined in stored samples drawn (n = 178) 30 days after the index exacerbation and associated with the risk of re-exacerbation during a 180-day follow-up period. RESULTS: IgG and subclass concentrations were significantly lower after 14 days vs. 5 days of glucocorticoid treatment. Patients with higher MBL concentrations were more likely to suffer from a future exacerbation (multivariable hazard ratio 1.03 per 200 ng/ml increase (95% confidence interval (CI) 1.00-1.06), p = 0.048), whereas ficolin-2 and IgG deficiency were not associated. The risk was most pronounced in patients with high MBL concentrations, IgG deficiency and 14 days of glucocorticoid treatment pointing towards an interactive effect of MBL and IgG deficiency in the presence of prolonged glucocorticoid treatment duration [Relative excess risk due to interaction 2.13 (95% CI - 0.41-4.66, p = 0.10)]. IgG concentrations were significantly lower in patients with frequent re-exacerbations (IgG, 7.81 g/L vs. 9.53 g/L, p = 0.03). CONCLUSIONS: MBL modified the short-term exacerbation risk after a recent acute exacerbation of COPD, particularly in the setting of concurrent IgG deficiency and recent prolonged systemic glucocorticoid treatment. Ficolin-2 did not emerge as a predictor of a future exacerbation risk.

Characterization of adult patients with IgG subclass deficiency and subnormal IgG2.

BACKGROUND: Adults with IgG subclass deficiency (IgGSD) with subnormal IgG2 are inadequately characterized. METHODS: We retrospectively analyzed observations in unrelated adults with IgGSD evaluated in a single hematology clinic (1991-2019) and selected those with subnormal serum IgG2 (<117 mg/dL (<1.2 g/L)) without corticosteroid therapy to describe: age; prevalence of women; upper/lower respiratory infection; autoimmune condition(s); atopy; other allergy; frequent or severe respiratory tract infection in first-degree relatives; IgG, IgG subclasses, IgA, and IgM; blood lymphocyte subpopulations; human leukocyte antigen (HLA)-A and -B types and haplotypes; and 23-valent pneumococcal polysaccharide vaccination (PPSV23) responses. We determined the prevalence of subnormal IgG2 among unrelated adults with IgGSD without corticosteroid therapy and compared general characteristics of those with and without subnormal IgG2. RESULTS: There were 18 patients (94.4% women) with subnormal IgG2. Mean age was 52 ± 11 y. Upper/lower respiratory infection occurred in 94.4%/74.8%, respectively. Autoimmune condition(s), atopy, other allergy, and frequent or severe respiratory infection in first-degree relatives occurred in 44.4%, 44.4%, 61.1%, and 22.2%, respectively. Median IgG2 was 105 mg/dL (83, 116). Subnormal IgG, IgG1, IgG3, IgG4, IgA, and IgM was observed in 66.7%, 50.0%, 100.0%, 5.6%, 33.3%, and 0%, respectively. Lymphocyte subpopulations were normal in most patients. HLA frequencies were similar in patients and controls. Three of 4 patients had no protective S. pneumoniae serotype-specific IgG levels before or after PPSV23. These 18 patients represent 7.6% of 236 adults with IgGSD. Prevalence of subnormal IgG, subnormal IgG3, and subnormal IgA was significantly greater in 18 adults with subnormal IgG2 than 218 adults without subnormal IgG2. Prevalence of subnormal IgM was significantly lower in patients with subnormal IgG2. CONCLUSIONS: Characteristics of adults with IgGSD with subnormal IgG2 include female predominance, other immunologic abnormalities, subnormal IgG3 and/or IgG1, lack of HLA-A and -B association, and suboptimal PPSV23 response.

ALG12-CDG: novel glycophenotype insights endorse the molecular defect.

Congenital disorders of glycosylation (CDG) are genetic diseases characterized by deficient synthesis (CDG type I) and/or abnormal processing (CDG type II) of glycan moieties linked to protein and lipids. The impact of the molecular defects on protein glycosylation and in turn on the clinical phenotypes of patients with CDG is not yet understood. ALG12-CDG is due to deficiency of ALG12 α1,6-mannosyltransferase that adds the eighth mannose residue on the dolichol-PP-oligosaccharide precursor in the endoplasmic reticulum. ALG12-CDG is a severe multisystem disease associated with low to deficient serum immunoglobulins and recurrent infections. We thoroughly investigated the glycophenotype in a patient with novel ALG12 variants and immunodeficiency. We analyzed serum native transferrin, as first line test for CDG and we profiled serum IgG and total serum N-glycans by a combination of consolidated (N-glycan analysis by MALDI MS) and innovative mass spectrometry-based protocols, such as GlycoWorks RapiFluor N-glycan analysis coupled with LC-ESI MS. Intact serum transferrin showed, as expected for a CDG type I defect, underoccupancy of N-glycosylation sites. Surprisingly, total serum proteins and IgG N-glycans showed some specific changes, consisting in accumulating amounts of definite high-mannose and hybrid structures. As a whole, ALG12-CDG behaves as a dual CDG (CDG-I and II defects) and it is associated with distinct, abnormal glycosylation of total serum and IgG N-glycans. Glycan profiling of target glycoproteins may endorse the molecular defect unraveling the complex clinical phenotype of CDG patients.

Clinical and Immunological Features of 78 Adult Patients with Primary Selective IgG Subclass Deficiencies.

The purpose of this study is to describe both clinical and immunological features in large cohort of adult patients with IgG subclass deficiency, and response to immunoglobulin therapy. This is a retrospective study of data obtained from electronic medical records and paper charts of 78 patients with IgG subclass deficiency seen and followed at our immunology clinics from 2010 to 2016. Both isolated selective IgG subclass deficiency as well as combined (two) subclass deficiencies were observed. IgG3 subclass deficiency, isolated and in combination with other IgG subclass deficiency, is the most frequent of IgG subclass deficiency. A majority of patients presented with upper and lower respiratory tract infections, especially chronic sinusitis. Both allergic and autoimmune manifestations are common; however, there is no subclass preference. The proportions and absolute numbers of CD3+ T cells, CD4+ T and CD8+ T cells, CD19+ B cells, and CD3-CD16+CD56+ NK cells were normal in the majority of patients in all IgG subclass deficiencies. Total serum IgG levels did not correlate with IgG subclass levels across all IgG subclass deficiencies. Anti-pneumococcal polysaccharide antibody responses were impaired in 56% of patients. IgG3 subclass deficiency is the most common IgG subclass deficiency, and anti-polysaccharide antibody responses are distributed among IgG subclasses with modest preference in IgG2 subclass. The majority of patients treated with immunoglobulin responded by reduction in frequency of infections and requirement of antibiotics.

Duration of frequent or severe respiratory tract infection in adults before diagnosis of IgG subclass deficiency.

Many adults with IgG subclass deficiency (IgGSD) experience long intervals of frequent/severe respiratory tract infection before IgGSD diagnosis, but reasons for delays in IgGSD diagnoses are incompletely understood. We performed a retrospective study of 300 white adults (ages ≥18 y) with IgGSD including frequency analyses of age at IgGSD diagnosis, duration of frequent/severe respiratory tract infection before IgGSD diagnosis, and age at onset of frequent/severe infection (calculated). We performed multivariable regressions on age at diagnosis, infection duration, and age at infection onset using these variables, as appropriate: sex; age at diagnosis; diabetes; autoimmune condition(s); atopy; allergy; corticosteroid use; body mass index; serum immunoglobulin isotype levels; blood lymphocyte subsets; three IgGSD-associated human leukocyte antigen-A and -B haplotypes; and referring physician specialties. Mean age at diagnosis was 50 ± 12 (standard deviation) y (median 50 y (range 19-79)). There were 247 women (82.3%). Mean infection duration at IgGSD diagnosis was 12 ± 13 y (median 7 y (range 1-66)). Mean age at infection onset was 38 ± 16 y (median 38 y (range 4, 76)). Age at infection onset was ≥18 y in 95.7% of subjects. Regressions on age at diagnosis and infection duration revealed no significant associations. Regression on age at infection onset revealed one positive association: age at diagnosis (p <0.0001). We conclude that the median duration of frequent/severe respiratory tract infection in adults before IgGSD diagnosis was 7 y. Older adults may be diagnosed to have IgGSD after longer intervals of infection than younger adults. Duration of frequent/severe respiratory tract infection before IgGSD diagnosis was not significantly associated with routine clinical and laboratory variables, including referring physician specialties.

Validation of Calculated Globulin (CG) as a Screening Test for Antibody Deficiency in an Italian University Hospital.

BACKGROUND: Morbidity and mortality of primary and secondary antibody deficiencies (AD) are frequently associated with diagnostic delays. These could be avoided by a combination of factors including a widespread and effective development in screening tests. METHODS: Calculated globulin (CG), derived from the difference between serum total protein and albumin levels, reflects immunoglobulin serum levels and has shown to have a predictive value in the early diagnosis of antibody deficiencies. This study investigated the possibility to use low levels of CG to detect antibody deficiency in an Italian University Hospital. RESULTS: First, we conducted an analysis of anonymized adult samples collected at our biochemistry laboratory with a range of calculated globulin levels from 15 to 22 g/l. A CG cut-off of 19 g/l detected subjects with IgG lower than 600 mg/dl with a sensitivity of 70% and a specificity of 75%. To further verify the clinical usefulness of CG, we retrospectively evaluated the relationship between CG values and serum IgG levels in 38 patients diagnosed with CVID at our Institution. Using a CG cut-off of 19 g/l, we detected antibody deficiency in 97.3% (37/38) of the subjects present in our cohort. CONCLUSION: Finally, we chose a CG value of 19 g/l as the cut-off for a prospective AD screening program. The results of this study show that a screening CG test can be used as a tool to reduce diagnostic delays, improve long-term prognosis and reduce the healthcare costs of antibody deficiency.

Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD.

BACKGROUND: The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts. METHODS: We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653). All samples were collected from clinically stable participants upon entry into both studies. IgG subclass deficiency was diagnosed when IgG subclass levels were below their respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24 g/L; and IgG4 < 0.052 g/L. To investigate the impact of IgG subclass levels on time to first exacerbation or hospitalization, we log-transformed IgG levels and performed Cox regression models, with adjustments for confounders. RESULTS: One or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%) participants in MACRO and STATCOPE, respectively. Lower IgG1 or IgG2 levels resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of 1.30 (95% CI, 1.10-1.54, p < 0.01) and 1.19 (95% CI, 1.05-1.35, p < 0.01), respectively in the MACRO study, with STATCOPE yielding similar results. Reduced IgG1 or IgG2 levels were also associated with increased risk of hospitalizations: the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15-2.02, p < 0.01) and 1.33 (95% CI, 1.08-1.64, p < 0.01), respectively for the MACRO study; in STATCOPE, only IgG2 was an independent predictor of hospitalization. In our multivariate Cox models, IgG3 and IgG4 levels did not result in significant associations for both outcomes in either MACRO or STATCOPE cohorts. CONCLUSIONS: Approximately 1 in 5 COPD patients had one or more IgG subclass deficiencies. Reduced IgG subclass levels were independent risk factors for both COPD exacerbations (IgG1 and IgG2) and hospitalizations (IgG2) in two COPD cohorts. TRIAL REGISTRATION: This study used serum samples from participants of the MACRO ( NCT00325897 ) and STATCOPE ( NCT01061671 ) trials.

Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment-free and overall survival in Chronic Lymphocytic Leukaemia.

Immune dysfunction attributed to hypogammaglobulinaemia is common in chronic lymphocytic leukaemia (CLL) and infection is a major contributor to morbidity and mortality. A higher incidence of multiple immunoglobulin and immunoglobulin G (IgG) subclass deficiency was associated with more advanced disease (P < 0·001 and P < 0·001, respectively) in a cohort of 147 CLL patients. Multiple immunoglobulin and IgG subclass deficiency were significantly associated with shorter treatment-free survival (TFS) (P < 0·001 and P = 0·006, respectively). The association between disease stage and immune dysfunction demonstrated by these data suggest aspects of immune deficiency correlate with disease severity and may be associated with shorter TFS in CLL.

The immunophenotypic fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives.

The etiology of primary antibody deficiencies is largely unknown. Beside rare monogenic forms, the majority of cases seem to have a more complex genetic basis. Whereas common variable immunodeficiency has been investigated in depth, there are only a few reports on milder primary antibody deficiencies such as idiopathic primary hypogammaglobulinemia and IgG subclass deficiency. We performed flow cytometric immunophenotyping in 33 patients with common variable immunodeficiency, 23 with idiopathic primary hypogammaglobulinemia and 21 with IgG subclass deficiency, as well as in 47 asymptomatic first-degree family members of patients and 101 unrelated healthy controls. All three groups of patients showed decreased memory B- and naïve T-cell subsets and decreased B-cell activating factor receptor expression. In contrast, circulating follicular helper T-cell frequency and expression of inducible T-cell co-stimulator and chemokine receptors were only significantly altered in patients with common variable immunodeficiency. Asymptomatic first-degree family members of patients demonstrated similar, albeit intermediate, alterations in naïve and memory B- and T-cell subsets. About 13% of asymptomatic relatives had an abnormal peripheral B-cell composition. Furthermore, asymptomatic relatives showed decreased levels of CD4+ recent thymic emigrants and increased central memory T cells. Serum IgG and IgM levels were also significantly lower in asymptomatic relatives than in healthy controls. We conclude that, in our cohort, the immunophenotypic landscape of primary antibody deficiencies comprises a spectrum, in which some alterations are shared between all primary antibody deficiencies whereas others are only associated with common variable immunodeficiency. Importantly, asymptomatic first-degree family members of patients were found to have an intermediate phenotype for peripheral B- and T-cell subsets.

The Challenge of Immunoglobulin-G Subclass Deficiency and Specific Polysaccharide Antibody Deficiency--a Dutch Pediatric Cohort Study.

PURPOSE: Immunoglobulin(Ig)G-subclass deficiency and specific polysaccharide antibody deficiency (SPAD) are among the most frequent causes of recurrent respiratory infections in children. Little is known about their prevalence, clinical presentation and prognosis. No study has been published in a Western-European nor in a mainly non-tertiary cohort until now. Therefore, we performed this observational cohort study in children recruited from secondary and tertiary pediatric practices all over The Netherlands. METHODS: Dutch pediatricians were monthly asked to report patients with IgG-subclass deficiency and/or SPAD. Demographic, clinical and laboratory characteristics were collected. Separate informed consent was asked from parents and children (≥ 12 years of age) for annual update of the medical status. RESULTS: 49 children with confirmed IgG-subclass deficiency and/or SPAD were included. The majority of children (69%) was reported by four (out of 12) secondary hospitals with a pediatric immunologist in the staff. 45 children had ≥ 1 low IgG-subclass level and 11 had SPAD. IgG2 deficiency was the most prevalent IgG-subclass deficiency (37/49;76%). 10% of these children already showed bronchiectasis. Two-thirds were male (33/49;67%, p = 0.015). From 10 years of age, only boys were left and only boys showed progressive immunodeficiency during follow-up (11/24; 46%). CONCLUSIONS: This is the first Western-European mainly non-tertiary cohort of children with IgG-subclass deficiency and/or SPAD. The disease course is not always benign, especially in boys. Most children were reported and managed in secondary hospitals with a pediatric immunologist in the staff. To identify more patients, the awareness of these diseases among general pediatricians should increase.

Overcoming recurrent spontaneous abortions in women suffering from IgG subclass deficiency: high efficiency of low dose intravenous immunoglobulins treatment.

PROBLEM: It's well known that iv. immunoglobulins may be useful to overcome habitual abortions, but the mechanisms at the base of a successful outcome and the likelihoods are still unknown. METHOD OF STUDY: In one hundred and sixty women with habitual abortions and one hundred and sixty healthy mothers, we evaluated blood IgG subclasses; among the patients, sixteen merely showed IgG subclass deficiency, after leaving out any autoimmunity and/or coagulation disorders. All the patients (100%) showed IgG3, twelve (75%) IgG1, eight (50%) IgG4 and six (37,5%) IgG2 deficiency; healthy control people's IgG subclasses fell in normal range in 156 women, but just four women showed IgG2 and IgG4 deficiency with neither immune deficiency's clinical marks nor increased vulnerability to infections. All the patients were treated with whole immunoglobulins iv. infusion (200 mg/kg/monthly) all over the pregnancy. RESULTS: The successful pregnancy rate is very high (>90%): 100% out of women showing IgG1 (12/12), 87,5% of IgG3 (14/16), 75% of IgG4 (6/8) and 66% of IgG2 deficiency (4/6) had successful pregnancies. The Odd's Ratio between IgG subclass deficiency and recurrent abortions is 4,33 with confidence interval of 95%; chi square value is 7.68 (p<0.025). CONCLUSIONS: Low dose immunoglobulin infusion is the only effective way to reach successful pregnancy, despite previous habitual abortions in patients suffering from IgG subclass deficiency without autoimmunity and/or coagulation disorders, likely restoring idiotype-antiidiotype network; showing evidence of IgG subclasses deficiency (mostly IgG1 and IgG3) may help identify patients who can benefit from iv. immunoglobulin treatment.

Comparisons of CVID and IgGSD: referring physicians, autoimmune conditions, pneumovax reactivity, immunoglobulin levels, blood lymphocyte subsets, and HLA-A and -B typing in 432 adult index patients.

Common variable immunodeficiency (CVID) and immunoglobulin (Ig) G subclass deficiency (IgGSD) are heterogeneous disorders characterized by respiratory tract infections, selective Ig isotype deficiencies, and impaired antibody responses to polysaccharide antigens. Using univariable analyses, we compared observations in 34 CVID and 398 IgGSD adult index patients (81.9% women) referred to a hematology/oncology practice. Similarities included specialties of referring physicians, mean ages, proportions of women, reactivity to Pneumovax, median serum IgG3 and IgG4 levels, median blood CD56+/CD16+ lymphocyte levels, positivity for HLA-A and -B types, and frequencies of selected HLA-A, -B haplotypes. Dissimilarities included greater prevalence of autoimmune conditions, lower median IgG, IgA, and IgM, and lower median CD19+, CD3+/CD4+, and CD3+/CD8+ blood lymphocytes in CVID patients. Prevalence of Sjögren's syndrome and hypothyroidism was significantly greater in CVID patients. Combined subnormal IgG1/IgG3 occurred in 59% and 29% of CVID and IgGSD patients, respectively. Isolated subnormal IgG3 occurred in 121 IgGSD patients (88% women). Logistic regression on CVID (versus IgGSD) revealed a significant positive association with autoimmune conditions and significant negative associations with IgG1, IgG3, and IgA and CD56+/CD16+ lymphocyte levels, but the odds ratio was increased for autoimmune conditions alone (6.9 (95% CI 1.3, 35.5)).

[Sinonasal polyposis associated with a deficiency subclass immunoglobulin G: Place of substitution immunoglobulins]. / Polypose nasosinusienne associée à un déficit en sous-classes d'Immunoglobuline G: place de la substitution en immunoglobulines polyvalentes.

PURPOSE: To study the effect of the introduction of a substitution by intravenous Immunoglobulins (Ig IV) at patients with immunoglobulins G (IgG) subclasses deficiency and nasal polyposis. MATERIAL AND METHODS: Prospective study concerning five patients with IgG subclasses deficiency and nasal polyposis treated by Ig IV. Rhinologic, otologic and pulmonary symptoms, exacerbations of nasal polyposis, chronic otitis and asthma as well as the number of antibiotics and corticoids treatments were counted during the Ig IV substitution. OBJECTIVES: To study the association between IgIV substitution and the number of exacerbations of nasal polyposis, chronic otitis, asthma and the number of antibiotics and corticoids treatments in patients with IgG subclasses deficiency and nasal polyposis. RESULTS: Five patients with a IgG subclass deficiency and nasal polyposis were substituted. The number of antibiotics and corticoids cures increased at one patient and remained stable at four others. The number of sinus, ear and lung infections as well as the global rhinologic score of symptoms and the endoscopic stage of the nasal polyposis remained stable. In the absence of efficiency of the treatment, this one was interrupted at the end of 6 months for patients n° 1 and n° 3, 24 months for patient n° 4 and 42 months for patient n° 5. CONCLUSION: The current study failed to highlight clinical improvement in patients wih IgG subclasses deficiency and nasal polyposis treated by Ig IV. A previous study had not allowed to find a link between IgG subclasses deficiency and severity of nasal polyposis, what seems to be confirmed by the absence of improvement brought during the substitution of this deficit in the current study.

Subcutaneous IgG replacement therapy is safe and well tolerated in lung transplant recipients.

Intravenous immunoglobulin (IVIG) replacement has been shown to decrease the risk of post-transplant infections secondary to hypogammaglobulinemia, however the use of subcutaneous immunoglobulin (SCIG) in this population has not been reported. A retrospective analysis of the efficacy and tolerability of subcutaneous immunoglobulin replacement on 10 lung-transplant recipients was performed. All 10 patients demonstrated an increase in IgG levels at three months that was sustained at 6-12 months with SCIG replacement therapy, with the majority (70%) tolerating infusion without complications. The results of this study suggest that subcutaneous IgG replacement therapy is a well tolerated alternative to IVIG.

Systemic atopy and immunoglobulin deficiency in Turkish patients with vernal keratoconjunctivitis.

PURPOSE: To determine the prevalence of systemic atopy and immunoglobulin (Ig) deficiencies in vernal keratoconjunctivitis (VKC). METHODS: Sixty-seven VKC subjects (79.1% boys) with a mean age of 11.3 ± 4.3 years were included. Serum Ig levels and specific IgE levels were measured using the nephelometric method and reversed enzyme immunoassay with sandwich ELISA technique, respectively. The patients underwent epidermal skin tests with commercial extracts. RESULTS: Family history of atopy and associated systemic allergies were detected in 32.8 and 40.3% of the subjects, respectively. Blood eosinophilia, elevated total, and specific IgE and positive skin tests were detected in 33.8, 42.2, 50, and 35% of the subjects, respectively. Out of 62 subjects, low levels of IgA, IgG, IgM, and IgG3 were detected in 12.9, 8, 6.5, and 1.6% of the patients, respectively. CONCLUSION: IgE-mediated mechanisms are involved in approximately 40% of VKC patients. A new finding was the higher incidence of Ig deficiency.