Truly selective primary IgM deficiency is probably very rare

Janssen, Lisanne M. A.; Macken, T; Creemers, M.C.W.; Pruijt, J.F.M.; Eijk, J.J.J. van; Vries, Esther de

doi:10.1111/cei.13065

Cited by 17 publications

(16 citation statements)

References 36 publications

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“…Patient 3 had low IgM levels. The patient whose IgG subsets could not be assessed was regarded as having possible selective IgM deficiency according to the relevant diagnostic criteria (23). High IgG levels (17.3 − 31 g/l) were detected in 6 patients (12.6%) while high IgM levels (2.53 − 4.81g/l) were detected in 4 patients (8.5%).…”

Section: Baseline Demographic Clinical and Laboratory Parameters Ofmentioning

confidence: 99%

Reverse Angle: Immunological Evaluation of Patients with Idiopathic Thrombocytopenic Purpura: A Retrospective Cohort Study

Aytekin¹,

Yıldız²,

Çölkesen³

et al. 2019

Asthma Allergy Immunol

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Objective: Primary Immune Thrombocytopenia (ITP, idiopathic thrombocytopenic purpura, immune thrombocytopenic purpura) is an acquired thrombocytopenia caused by anti-platelet antibodies. The diagnosis of ITP may be challenging due to the various potential causes of thrombocytopenia, some of which are overlooked. Immunodeficiencies are also a rare cause of ITP. Although autoimmunity and, therefore, ITP are a common complication in primary immunodeficiency (PI) patients, there are not many publications in the literature that examine the frequency of PI in ITP patients and the immune abnormalities in these patients. Materials and Methods:Forty-five patients with ITP (F: 37 [78.7%], M: 10 [21.3%]) were included in the study (age 42.9 ± 15.9).Results: At least one antibody deficiency was detected in 7 patients (14.9%), and following further investigations, 2 patients (4.3%) were diagnosed with CVID, 3 (6.4%) with IgG deficiency, 1 (2.1%) with selective IgA deficiency and 1 (2.1%) with possible IgM deficiency. Immunoglobulin levels were normal while at least one abnormality was detected in 20 patients (42.6%) in peripheral lymphocyte subset analyses. The most common abnormality in this patient group was a reduced percentage of CD4+ T-cells (9 patients, 45% of patients with PLS abnormalities, 19.1% of all patients). CD3+ T-cell rates in 8 patients (17.8%), CD19+ B-cell rates in 6 (12.8%), CD3-CD16+56+ natural killer cell rates in 4 (8.5%), and CD4/CD8 cell ratios in 7 (14.9%) were reduced. In addition, the CD8+ T-cell rate in 8 patients (17%) was above the reference ranges. Conclusion:Adult patients who are diagnosed with ITP may develop a variety of immunological abnormalities in addition to hypogammaglobulinemia. Therefore, clinicians should not overlook immunological evaluation in the etiological investigation of ITP and should closely monitor patients with immunological abnormalities.

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Section: Baseline Demographic Clinical and Laboratory Parameters Ofmentioning

confidence: 99%

Reverse Angle: Immunological Evaluation of Patients with Idiopathic Thrombocytopenic Purpura: A Retrospective Cohort Study

Aytekin¹,

Yıldız²,

Çölkesen³

et al. 2019

Asthma Allergy Immunol

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“…The immunological and clinical phenotype of sIgMD is very heterogeneous and patients can remain asymptomatic [ 49 ]. Similar to sIgAD, patients with sIgMD often present with recurrent respiratory problems [ 49 , 50 ]. In a cohort of 17 sIgMD patients, recurrent upper respiratory tract infections were observed in 5 out of 6 patients with undetectable IgM levels (<0.05 g/L) [ 49 ].…”

Section: Immunoglobulin Deficienciesmentioning

confidence: 99%

Limited Innovations After More Than 65 Years of Immunoglobulin Replacement Therapy: Potential of IgA- and IgM-Enriched Formulations to Prevent Bacterial Respiratory Tract Infections

2018

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Patients with primary immunoglobulin deficiency have lower immunoglobulin levels or decreased immunoglobulin function, which makes these patients more susceptible to bacterial infection. Most prevalent are the selective IgA deficiencies (~1:3,000), followed by common variable immune deficiency (~1:25,000). Agammaglobulinemia is less common (~1:400,000) and is characterized by very low or no immunoglobulin production resulting in a more severe disease phenotype. Therapy for patients with agammaglobulinemia mainly relies on prophylactic antibiotics and the use of IgG replacement therapy, which successfully reduces the frequency of invasive bacterial infections. Currently used immunoglobulin preparations contain only IgG. As a result, concurrent IgA and IgM deficiency persist in a large proportion of agammaglobulinemia patients. Especially patients with IgM deficiency remain at risk for recurrent infections at mucosal surfaces, which includes the respiratory tract. IgA and IgM have multiple functions in the protection against bacterial infections at the mucosal surface. Because of their multimeric structure, both IgA and IgM are able to agglutinate bacteria efficiently. Agglutination allows for entrapment of bacteria in mucus that increases clearance from the respiratory tract. IgA is also important for blocking bacterial adhesion by interfering with bacterial adhesion receptors. IgM in its place is very well capable of activating complement, therefore, it is thought to be important in complement-mediated protection at the mucosal surface. The purpose of this Mini Review is to highlight the latest advances regarding IgA- and IgM-enriched immunoglobulin replacement therapy. We describe the different IgA- and IgM-enriched IgG formulations, their possible modes of action and potential to protect against respiratory tract infections in patients with primary immunoglobulin deficiencies.

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“…When these criteria are completely fulfilled, we refer to this condition as “truly selective primary IgM deficiency” ( true sIgMdef), albeit we consider the absence of clinical signs suggesting a T cell defect a sufficient criterion. Only six of 261 (2%) patients described in the literature with “IgM deficiency” completely fulfil the defined criteria for true sIgMdef . For many reported patients, the diagnosis is either uncertain, which means that the ESID criteria are not fulfilled completely because data on IgG subclasses and/or vaccination responses are lacking (we refer to the latter as “ possible sIgMdef”), or their IgM deficiency is not selective, because other antibody abnormalities are present; these cases fit the ESID classification “unclassified primary antibody deficiency” ( unPAD ) …”

Section: Introductionmentioning

confidence: 99%

“…The reported patients are almost always symptomatic and most of them presented with infections . We recently showed in a secondary centre population that decreased serum IgM levels can often incidentally be found in asymptomatic adults . The determination of the clinical significance of sIgMdef is not only challenged by the rarity and highly variable phenotype of this primary immunodeficiency, but also by the different criteria for “selective IgM deficiency” that are used in the literature .…”

Section: Introductionmentioning

confidence: 99%

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Challenges in investigating patients with isolated decreased serum IgM: The SIMcal study

2019

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The clinical consequences of isolated decreased serum immunoglobulin (Ig)M are not sufficiently known. Therefore, it is difficult to determine the clinical policy following such a finding. Only few reported IgM‐deficient patients fulfil the European Society for Immunodeficiencies (ESID) diagnostic criteria for selective IgM deficiency (true sIgMdef), or their diagnosis is uncertain due to insufficient laboratory data (possible sIgMdef). Decreased serum IgM is often incidentally found in asymptomatic adults. The objective of our study was to further characterize true sIgMdef and to compare the European data collected through the ESID Registry community (tertiary centres) to our previously published Dutch cohort (secondary centre). Fifteen centres (12 countries) participated with 98 patients. Patients were excluded if serum IgM was only determined once (n = 14), had normalized (n = 8), or if they also had other immunological abnormalities (n = 15). Ten patients (5 adults) completely fulfilled the ESID criteria for true sIgMdef. Age‐matched cut‐off values varied widely between centres; when using the ESID diagnostic protocol reference values, only six patients (five adults) had true sIgMdef. Because of these small numbers, further analyses were performed in patients with true or possible sIgMdef (13 adults, 48 children). Respiratory infections were commonly reported at presentation (adults 54%, children 60%). Symptomatic adults had lower serum IgM levels (mean 0.27 g/L, 95% CI 0.22‐0.31) than those without symptoms (mean 0.33 g/L, 95% CI 0.30‐0.36; P = 0.02). To be able to explore the clinical consequences of true sIgMdef, we should fully analyse and accurately describe those patients in whom a decreased serum IgM is found.

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Truly selective primary IgM deficiency is probably very rare

Cited by 17 publications

References 36 publications

Reverse Angle: Immunological Evaluation of Patients with Idiopathic Thrombocytopenic Purpura: A Retrospective Cohort Study

Reverse Angle: Immunological Evaluation of Patients with Idiopathic Thrombocytopenic Purpura: A Retrospective Cohort Study

Limited Innovations After More Than 65 Years of Immunoglobulin Replacement Therapy: Potential of IgA- and IgM-Enriched Formulations to Prevent Bacterial Respiratory Tract Infections

Challenges in investigating patients with isolated decreased serum IgM: The SIMcal study

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