Low immunoglobulin E flags two distinct types of immune dysregulation

Abstract

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.

Immunoglobulin G and Subclasses as Potential Biomarkers in Metastatic Melanoma Patients Starting Checkpoint Inhibitor Treatment

“…Low serum IgG2 and IgG4, but not IgG3, have been recently shown to be associated with the clinical diagnosis of antibody deficiency in a retrospective analysis. 24 Thus, patients with low IgG2 and IgG4 may suffer from a mild form of immunodeficiency that was previously not recognized in these patients. It is interesting to note that, in 2013, Karagiannis et al 25 described an association between high IgG4 levels and poor survival in 57 patients diagnosed with stage I-IV malignant melanoma.…”

The other side of the coin: IgE deficiency, a susceptibility factor for malignancy occurrence

“…33 May be associated with other immunodeficiencies Ataxia telangiectasia, 31 Common Variable Immunodeficiency (CVID), 38 IgA deficiency, 39 IgG subclass deficiency. 40 When all other immunoglobulins are normal, the condition is called “Selective IgE deficiency”. Patients might have environmental allergy-like symptoms Environmental allergy-like symptoms (e.g.…”

“…Ataxia telangiectasia, 31 Common Variable Immunodeficiency (CVID), 38 IgA deficiency, 39 IgG subclass deficiency. 40 …”

“…To answer these questions, the cause of IgE deficiency needs to be elucidated. Existent data describe 2 categories of patients with IgE deficiency: those with selective IgE deficiency when all other immunoglobulins are normal, and those with an associated humoral immunodeficiency, such as common variable immunodeficiency (CVID), 38 IgA deficiency, 39 or IgG subclass deficiency 40 ( Table 1 ). Interestingly, although malignancy is common in CVID patients, the higher rate of cancer in IgE deficient individuals was unrelated to the CVID diagnosis.…”

Spectrum of Disease Manifestations in Patients with Selective Immunoglobulin E Deficiency

“…An excess of IgE (>100 kU/L) can be established but, in contrast to the other immunoglobulins, there is no generally accepted minimum level to establish an IgE deficiency. In various studies in the literature, different cut-off points have been used to define IgE deficiency [ 15 , 16 , 17 , 18 , 19 ]. Most clinicians do not attribute any pathological significance to very low IgE values, even those that are unquantifiable (≤2 kU/L), which are usually considered as “normal”.…”