Current screening approaches for antibody deficiency

Holding, Stephen; Jolles, Stephen

doi:10.1097/aci.0000000000000222

Cited by 20 publications

(20 citation statements)

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“…IgG, IgA and/or IgM) below the reference range for age [10,11]. In line with these reports, a recent review concluded that low IgE levels should be considered as a clinical laboratory 'flag' to screen for antibody deficiency [12]. Some of these studies, however, may have been biased, as they correlated only immunoglobulin levels that had been measured for unspecified clinical reasons.…”

Section: Introductionmentioning

confidence: 65%

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Low immunoglobulin E flags two distinct types of immune dysregulation

Elkuch

Greiff

Berger

et al. 2017

Clinical and Experimental Immunology

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1These authors contributed equally to this study. SummaryDuring the last two decades, hyper-immunoglobulin (Ig)E syndromes have been characterized clinically and molecularly in patients with genetically determined primary immunodeficiencies. However, the detection of low IgE levels, defined here as below detection limit in the routine clinical immunology laboratory, has received little attention. We analysed the association of serum IgA, IgM and IgG levels (including IgG subclasses) with low, normal or high serum IgE levels in patients evaluated in a singlecentre out-patient immunodeficiency and allergy clinic. The correlation of serum IgE levels with IgG subclasses depended on the clinical phenotype. In patients with immunodeficiencies, IgE correlated with IgG2 and IgG4 but not with IgG3. In contrast, in patients referred for signs of allergy, IgE correlated with IgG3 but not with IgG2. A low IgE result was associated with low IgG3 and IgG4 in allergy referrals, while immunodeficiency referrals with a low IgE result had significantly lower IgG1, IgG2 and IgG4 levels. Hierarchical clustering of non-IgE immunoglobulin profiles (IgM, IgA, IgG, IgG1-4) validated that non-IgE immunoglobulin levels predict the clinic referral, i.e. phenotype, of low-IgE patients. These results suggesto guide the clinical management of patients with low serum IgE levels.

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Section: Introductionmentioning

confidence: 65%

“…Patients with antibody deficiencies are often diagnosed with a significant delay [12,25]. This may be partly because the health-care professionals involved in evaluating these patients are unaware of this differential diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Low immunoglobulin E flags two distinct types of immune dysregulation

Elkuch

Greiff

Berger

et al. 2017

Clinical and Experimental Immunology

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“…The most notable ones include: (i) hypergammaglobulinemia should prompt the consideration of HIV infection, especially if greater than 30 g/L, (ii) low-background optical density on the IgA TTG assay or low-background staining on antiendomysial IgA testing should lead to the suspicion of IgA deficiency, (iii) very low IgE (<2 IU) when testing for allergy should make clinicians check the other immunoglobulins, as approximately 7% of those patients may have an antibody deficiency, (iv) patients with low-globulin gap should undergo a follow-up measurement of IgG concentration as 89% of patient with a globulin gap <18 g/L had an IgG <6 g/L. Prompt use of the globulin gap has been shown to improve early detection of hypogammaglobulinemia [11,12], (v) low monocyte counts have been associated with a recently described PID caused by GATA-2 deficiency, and (iv) idiopathic thrombocytopenic purpura can be the presenting feature of primary or secondary immune deficiencies.…”

Section: Screeningmentioning

confidence: 99%

Immune deficiency in chronic rhinosinusitis: screening and treatment

Chiarella

Grammer

2016

Expert Review of Clinical Immunology

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Introduction Chronic rhinosinusitis (CRS) is a prevalent disease with a high annual cost of treatment. Immune deficiencies are more common in individuals with CRS and should be especially considered in those patients who are refractory to medical and surgical therapy. Areas covered We performed a literature search in PubMed of the terms “immunodeficiency” and “sinusitis” or “rhinosinusitis” from 2006 through March 2016. All abstracts were reviewed to determine if they pertained to human disease; relevant articles were evaluated in their entirety and included in this review. Expert commentary CRS is a common disease; in those patients with frequent exacerbations or who are refractory to treatment, an immunodeficiency evaluation should be considered. Treatment includes vaccination, antibiotic therapy, immunoglobulin replacement and surgery.

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“…This group of proteins is a valuable serum biomarker for several pathologies that affect directly or have repercussions in the immune system. For instance, decreased levels of IgG may be associated with primary antibody deficiency, protein-losing enteropathies, nephrotic syndrome, or iatrogenic hypogammaglobulinemia as a consequence of immunosuppressant, anti-convulsant, or cytotoxic therapies [3][4][5][6][7]. The level of serum IgG is also a valuable predictor for the risk of infection in transplant recipients [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…The level of serum IgG is also a valuable predictor for the risk of infection in transplant recipients [8][9][10]. Moreover, high IgG levels are indicators of autoimmunity (e.g., demyelinating diseases, lupus erythematosus), chronic infection, liver diseases (e.g., autoimmune hepatitis), and lymphoproliferative disorders (e.g., multiple myeloma) [3,[11][12][13][14]. The early diagnosis of these conditions is a key factor to minimize the risk of permanent organ damage and to proceed with adequate therapy, accounting for less morbidity and mortality [14,15].…”

Section: Introductionmentioning

confidence: 99%

Micro-bead injection spectroscopy for label-free automated determination of immunoglobulin G in human serum

et al. 2017

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Immunoglobulin G (IgG) represents the major fraction of antibodies in healthy adult human serum, and deviations from physiological levels are a generic marker of disease corresponding to different pathologies. Therefore, screening methods for IgG evaluation are a valuable aid to diagnostics. The present work proposes a rapid, automatic, and miniaturized method based on UV-vis micro-bead injection spectroscopy (μ-BIS) for the real-time determination of human serum IgG with label-free detection. Relying on attachment of IgG in rec-protein G immobilized in Sepharose 4B, a bioaffinity column is automatically assembled, where IgG is selectively retained and determined by on-column optical density measurement. A "dilution-and-shoot" approach (50 to 200 times) was implemented without further sample treatment because interferences were flushed out of the column upon sample loading, with minimization of carryover and cross-contamination by automatically discarding the sorbent (0.2 mg) after each determination. No interference from human serum albumin at 60 mg mL in undiluted sample was found. The method allowed IgG determination in the range 100-300 μg mL (corresponding to 5.0-60 mg mL in undiluted samples), with a detection limit of 33 μg mL (1.7 mg mL for samples, dilution factor of 50). RSD values were < 9.4 and < 11.7%, for intra and inter-assay precision, respectively, while recovery values for human serum spiked with IgG at high pathological levels were 97.8-101.4%. Comparison to commercial ELISA kit showed no significant difference for tested samples (n = 8). Moreover, time-to-result decreased from several hours to < 5 min and analysis cost decreased 10 times, showing the potential of the proposed approach as a point-of-care method. Graphical abstract Micro-Bead Injection Spectroscopy method for real time, automated and label-free determination of total serum human Immunoglobulin G (IgG). The method was designed for Lab-on-Valve (LOV) platforms using a miniaturised protein G bioaffinity separative approach. IgG are separated from serum matrix components upon quantification with low non-specific binding in less than 5 min.

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Current screening approaches for antibody deficiency

Abstract: There is a strong case for the use of calculated globulin in screening for antibody deficiency. Further work is required to integrate laboratory results with clinical data to reduce diagnostic delay in patients with hitherto unsuspected antibody deficiency.

Cited by 20 publications

References 48 publications

Low immunoglobulin E flags two distinct types of immune dysregulation

Low immunoglobulin E flags two distinct types of immune dysregulation

Immune deficiency in chronic rhinosinusitis: screening and treatment

Micro-bead injection spectroscopy for label-free automated determination of immunoglobulin G in human serum

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