IgG4 subclass deficiency

BACKGROUND AND AIM: Treating hemophilia A patients who develop inhibitors remains a clinical challenge. A mouse model of hemophilia A can be used to test the efficacy of strategies for inhibitor suppression, but the differences in the immune systems of mice and humans limit its utility. To address this shortcoming, we established a humanized NOD/SCID-IL2rγnull hemophilia A (hu-NSG-HA) mouse model with a severely deficient mouse immune system presenting a patient's adapted immune cells...

Immunoglobulin G (IgG) subclasses have been suggested to confer naturally acquired immunity to Plasmodium falciparum malaria. Cytophilic IgG1 and IgG3 with their potential for opsonization, phagocytosis, and antibody-dependent cellular inhibition in association with monocytes have been suggested to have a critical role in malaria. The potential for production of antibodies is influenced by micronutrient status. This study aimed at exploring the effect of micronutrients, particularly zinc status, on the profiles of IgG subclasses in 304 Tanzanian children aged ≤ 5 years...

S. pneumoniae is an important human pathogen which has a polysaccharide capsule with virulent properties. This work aims to estimate the titres of S. pneumoniae specific IgG and IgA isotypes, with respect to age and sex. An in-house whole bacterial cell ELISA was used for the determination of relative levels and endpoint titres of IgG subclasses and IgA1 subclass specific for S. pneumoniae serogroup 1, and to quantify specific IgG1 and IgG2 levels. Significantly lower anti-pneumococcus IgG1 titres were found in older individuals, which was more pronounced in men...

BACKGROUND: Immunoglobulin G (IgG) deficiency increases the risk of acute exacerbations and mortality in chronic obstructive pulmonary disease (COPD). However, the impact of IgG subclass deficiency on mortality in COPD is unknown. Here, we determined which IgG subclass, if any, is associated with increased risk of mortality in COPD. METHODS: We measured serum IgG subclass concentrations of 489 hospitalized patients with COPD who were enrolled in the Rapid Transition Program (clinicaltrials...

We report a case of IgG4-RD in a patient with high IgG4 levels, low functional antibodies, and low IgM levels. He presented with bilateral orbital pseudotumors and, after initial improvement on corticosteroids, relapsed with recurrent pleural effusion and pelvic pseudotumor. He had a grossly elevated serum IgG (1905 mg/dl) with elevations in all IgG subclasses but marked elevation in IgG4 (412 mg/dl), low IgM, and low pneumococcal antibodies. Orbital mass biopsy showed polyclonal lymphocytic infiltration and increased IgG4 plasma cells...

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multi-systemic disease characterized by debilitating fatigue that is not relieved by rest. The causes of the disease are still largely unexplained, and no causative treatment is currently available. Changes in the immune response are considered as fundamental in the development of ME/CFS. Thus, we aimed to evaluate the immunological profile of ME/CFS patients in a retrospective data analysis. As part of the routine workup for ME/CFS patients, a differential blood count, leukocyte subtyping, and quantification of immunoglobulins and IgG subclasses, as well as a complement analysis, was performed...

BACKGROUND: Factors associated with IgG levels in adults with IgG subclass deficiency (IgGSD) are incompletely understood. We studied adults with IgGSD with subnormal IgG1 only, subnormal IgG1/IgG3, or subnormal IgG3 only without other subnormal IgG subclasses, IgA, or IgM. We compiled: age; sex; autoimmune condition(s) (AC); atopy; IgG, IgG subclasses, IgA, IgM; IgGsum (IgG1 + IgG2 + IgG3 + IgG4); and D (percentage difference between IgGsum and IgG). We compared attributes of patients with/without subnormal IgG (< 7...

BACKGROUND: In contrast to intense investigations of galactose-deficient immunoglobulin A (IgA)1 specific immunoglobulin G (IgG), little is known about the IgG subclasses in IgA nephropathy (IgAN). Low IgG4 levels in IgAN were noticed in our preliminary experiment. We aimed to verify the low IgG4 levels and investigate the related immune mechanism in IgAN. METHODS: A total of 112 healthy controls (HC) and 112 newly diagnosed IgAN patients were enrolled in this study...

Anthrax vaccine adsorbed (AVA) is a significant line of defense against bioterrorist attack from Bacillus anthracis spores. However, in a subset of individuals, this vaccine may produce a suboptimal quantity of anti-protective antigen (PA), antibodies that are poorly neutralizing, and/or antibody titers that wane over time, necessitating annual boosters. To study individuals with such poor responses, we examine the properties of anti-PA in a subset of vaccinated individuals that make significant quantities of antibody but are still unable to neutralize toxin...

Immunoglobulins and antibodies to immunoglobulins (autoimmunoglobulins) have been identified to be implicated in the pathogenesis of rheumatoid arthritis (RA). Immunoglobulin deficiencies have been suggested to account for the increased risk of infections in RA patients. This study was carried out to determine the prevalence of immunoglobulin deficiencies in patients with RA and the identification of putative contributing factors. Immunoglobulin levels in blood samples of patients with rheumatoid arthritis were evaluated by an immunonephelometric assay...

Despite the pandemic status of COVID-19, there is limited information about host risk factors and treatment beyond supportive care. Immunoglobulin G (IgG) could be a potential treatment target. Our aim was to determine the incidence of IgG deficiency and associated risk factors in a cohort of 62 critically ill patients with COVID-19 admitted to two German ICUs (72.6% male, median age: 61 yr). Thirteen (21.0%) of the patients displayed IgG deficiency (IgG < 7 g/L) at baseline (predominant for the IgG1, IgG2, and IgG4 subclasses)...

Background: The most important infectious trigger of asthma is the virus and patients with immunoglobulin deficiencies are prone to recurrent respiratory infections. Objective: We investigated the relationship between immunoglobulin G subclass and recurrent respiratory symptom exacerbation and explored possible therapeutic effects of intravenous immunoglobulin administration. Methods: Twenty-eight infants less than 24 months old with 2 or more recurrent wheezing episodes (infantile wheezer group) and 29 asthmatic children aged 24 months to 15 years (bronchial asthma [B-asthma] group) visited our hospital from October 2010 to January 2018...

CH50 is a screening assay for the activation of the classical complement pathway, the immunoglobulins-mediated one, activated in several inflammatory diseases. Adult growth hormone deficiency (aGHD) is recognized as a chronic inflammatory condition, although poorly evaluated under the profile of inflammatory biomarkers. The aim of this case-control observational study is to analyze CH50 and immunoglobulins G (IgG) subclasses production in aGHD, comparing this condition to healthy controls. 38 subjects were included and divided as follows: aGHD (n = 18, 6 females and 12 males); healthy controls (n = 20, 10 females and 10 males)...

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...

BACKGROUND: Immunoglobulin G subclass 4 (IgG4) is hypothesized to play an immunomodulatory role, downregulating humoral immune responses. The role of this anti-inflammatory molecule in inflammatory bowel disease (IBD) has not been fully characterized. We sought to define alterations in serum IgG4 in patients with IBD and their association with multiyear disease severity. METHODS: We analyzed metadata derived from curated electronic health records from consented patients with IBD prospectively followed at a tertiary center over a 10-year time period...

Recurrent respiratory tract infections (RTI) are one of the most common diseases in childhood. Frequent infections adversely affect the development of a child and may lead to suspicion of immunodeficiency. An additional allergy component is thought conducive to infection occurrence. In this study, we retrospectively assessed medical records of 524 children hospitalized with RTI. Patients were divided into two groups: RTI-alone (n = 394) and RTI with a history of allergy (n = 130). Overall, we found that a great majority of children with RTI had the immunoglobulin G within the normal limit, irrespective of allergy...

BACKGROUND: Serum immunoglobulin G (IgG) concentrations are integral to the workup of immune deficiencies and IgG4-related disease (IgG4-RD). Demographic differences in IgG concentrations are poorly described but can influence test interpretation, contribute to racial disparities in primary immunodeficiency diagnosis, and explain demographic differences in IgG concentrations in IgG4-RD. OBJECTIVE: To assess differences in IgG and IgG subclass concentrations according to sex and race...

The immune pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains obscure. Our aim was to compare humoral immunity and white blood cell counts in patients with CRSwNP and controls. A prospective case-control study was carried out in 37 patients with CRSwNP and 34 controls without CRS. Clinical data were gathered through a systematic interview. Computed tomography scan, skin prick test, spirometry, and immunological parameters (leukocyte differential count, immunoglobulin classes, and immunoglobulin [Ig] G subclasses) in serum specimens were obtained...

IgG4-related disease (IgG4-RD) is characterized by multiorgan irreversible damage resulting from tissue-specific infiltration of IgG4+ plasma cells and cytotoxic T lymphocytes (CTLs). However, whether IgG4 antibody (Ab) contributes to the inflammation remains unclear. In this study, we established a mouse model enables to evaluate the pathogenic function of IgG4 Abs in response to a tissue-specific autoantigen using recombinant OVA-specific human IgG4 monoclonal Ab (rOVA-hIgG4 mAb) and the mice expressing OVA of the pancreatic islet (RIP-mOVA mice)...

BACKGROUND: Immunoglobulin (Ig) therapy is highly effective in reducing the frequency and severity of infections. However, a subset of patients does not respond adequately. OBJECTIVE: To determine in adult patients with primary hypogammaglobulinemia (a) if failure to reconstitute IgG subclass(es) is associated with inadequate clinical response, (b) whether reconstitution of IgG subclasses differs between routes of Ig administration, (c) which subclasses contribute to low total IgG, and (d) what are the most commonly impaired Streptococcus pneumoniae serotypes...