Assessing Disease Severity in Common Variable Immunodeficiency Disorders (CVID) and CVID-Like Disorders

Ameratunga, Rohan

doi:10.3389/fimmu.2018.02130

Cited by 49 publications

(53 citation statements)

References 41 publications

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“…However, albumin levels were confirmed as normal in 12 of these patients. Food allergies have been rarely described in CVID patients and IgE levels are generally low, and this may an important clue to THI . THI patients with food allergies had the highest rate of asthma, which is a known association (Table ).…”

Section: Discussionmentioning

confidence: 99%

Transient hypogammaglobulinaemia of infancy: many patients recover in adolescence and adulthood

Ameratunga

Ahn

Steele

et al. 2019

Clinical and Experimental Immunology

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Summary Transient hypogammaglobulinaemia of infancy (THI) is a relatively rare disorder where there is an exaggeration of the physiological nadir of immunoglobulin (Ig)G between loss of transplacentally acquired maternal IgG and production by the infant. Patients may be vulnerable to infections during the period of hypogammaglobulinaemia. The precise time to recovery in all infants is currently unknown. We sought to determine the clinical features and time–course of recovery for patients with THI. We reviewed our experience with THI over the last three decades in order to describe clinical and laboratory features, as well as the time–course of recovery. Forty‐seven patients were identified with THI. Only thirty‐seven per cent remitted by 4 years of age, while some patients did not recover until the third or fourth decade. In keeping with previous studies, the majority (25 of 47) presented with recurrent infections, nine had a family history of immunodeficiency and 13 had adverse reactions to food as their dominant clinical manifestation. Chronic tonsillitis developed in 10 patients and symptoms improved following surgery. The group with food allergies recovered sooner than those presenting with infections or with a family history immunodeficiency. Eight patients failed to respond to at least one routine childhood vaccine. Two have IgA deficiency and four individuals recovering in adolescence and adulthood continue to have borderline/low IgG levels. None have progressed to common variable immunodeficiency disorders (CVID). THI is a misnomer, as the majority do not recover in infancy. Recovery from THI can extend into adulthood. THI must be considered in the differential diagnosis of adolescents or young adults presenting with primary hypogammaglobulinemia.

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Section: Discussionmentioning

confidence: 99%

Transient hypogammaglobulinaemia of infancy: many patients recover in adolescence and adulthood

Ameratunga

Ahn

Steele

et al. 2019

Clinical and Experimental Immunology

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“…Detailed history was obtained including the reasons for testing, when symptoms began, medication history, hospitalizations, numbers and severity of infections and any treatment received. Particular emphasis was placed on target organ damage (1). Patients were asked to undertake a comprehensive set of laboratory tests as part of their diagnostic evaluation.…”

Section: Methodsmentioning

confidence: 99%

“…They are at risk of bronchiectasis and chronic upper respiratory tract disease. A significant minority experience a broad range of autoimmune and inflammatory disorders (1).…”

Section: Introductionmentioning

confidence: 99%

The Natural History of Untreated Primary Hypogammaglobulinemia in Adults: Implications for the Diagnosis and Treatment of Common Variable Immunodeficiency Disorders (CVID)

et al. 2019

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Background: Adults with primary hypogammaglobulinemia are frequently encountered by clinicians. Where IgG levels are markedly decreased, most patients are treated with subcutaneous or intravenous immunoglobulin (SCIG/IVIG), because of the presumed risk of severe infections. The natural history of untreated severe asymptomatic hypogammaglobulinemia is thus unknown. Similarly, there are no long-term prospective studies examining the natural history of patients with moderate reductions in IgG. Methods: In 2006, we began a prospective cohort study of patients with symptomatic and asymptomatic reductions in IgG who were not immediately commenced on SCIG/IVIG. Over the course of 12 years, 120 patients were enrolled in the NZ hypogammaglobulinemia study (NZHS) including 59 who were asymptomatic. Results: Five patients with profound primary hypogammaglobulinemia (IgG < 3 g/l), who were not on regular SCIG/IVIG have remained well for a mean duration of 139 months. This study has also shown most asymptomatic patients with moderate hypogammaglobulinemia (IgG 3.0–6.9 g/l) have been in good health for a mean observation period of 96 months. We have only identified one asymptomatic patient with moderate hypogammaglobulinemia who experienced progressive decline in IgG levels to <3 g/l and was accepted for IVIG replacement. Prospective monitoring has shown that none have suffered catastrophic infections or any of the severe autoimmune or inflammatory sequelae associated with Common Variable Immunodeficiency Disorders (CVID). Unexpectedly, 18.1% of asymptomatic and 41.6% of symptomatic hypogammaglobulinemic patients spontaneously increased their IgG into the normal range (≥7.0 g/l) on at least one occasion, which we have termed transient hypogammaglobulinemia of adulthood (THA). In this study, vaccine challenge responses have correlated poorly with symptomatic state and long-term prognosis including subsequent SCIG/IVIG treatment. Conclusions: In spite of our favorable experience, we recommend patients with severe asymptomatic hypogammaglobulinemia are treated with SCIG/IVIG because of the potential risk of severe infections. Patients with moderate asymptomatic hypogammaglobulinemia have a good prognosis. Patients with symptomatic hypogammaglobulinemia are a heterogeneous group where some progress to SCIG/IVIG replacement, while many others spontaneously recover. This study has implications for the diagnosis and treatment of CVID.

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“…Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous group of disorders where patients present hallmark loss of at least two immunoglobulin isotypes (IgG and IgA and/or IgM) and impaired specific antibody production . CVID are the most prevalent cause of hypogammaglobulinemia in adults, affecting ≥ 1 : 25 000 .…”

Section: Introductionmentioning

confidence: 99%

Chemical chaperones reverse early suppression of regulatory circuits during unfolded protein response in B cells from common variable immunodeficiency patients

Bhatt

Stan²,

Pinhata

et al. 2020

Clinical and Experimental Immunology

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Summary B cells orchestrate pro‐survival and pro‐apoptotic inputs during unfolded protein response (UPR) to translate, fold, sort, secrete and recycle immunoglobulins. In common variable immunodeficiency (CVID) patients, activated B cells are predisposed to an overload of abnormally processed, misfolded immunoglobulins. Using highly accurate transcript measurements, we show that expression of UPR genes and immunoglobulin chains differs qualitatively and quantitatively during the first 4 h of chemically induced UPR in B cells from CVID patients and a healthy subject. We tested thapsigargin or tunicamycin as stressors and 4‐phenylbutyrate, dimethyl sulfoxide and tauroursodeoxycholic acid as chemical chaperones. We found an early and robust decrease of the UPR upon endoplasmic reticulum (ER) stress in CVID patient cells compared to the healthy control consistent with the disease phenotype. The chemical chaperones increased the UPR in the CVID patient cells in response to the stressors, suggesting that misfolded immunoglobulins were stabilized. We suggest that the AMP‐dependent transcription factor alpha branch of the UPR is disturbed in CVID patients, underlying the observed expression behavior.

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Assessing Disease Severity in Common Variable Immunodeficiency Disorders (CVID) and CVID-Like Disorders

Cited by 49 publications

References 41 publications

Transient hypogammaglobulinaemia of infancy: many patients recover in adolescence and adulthood

Transient hypogammaglobulinaemia of infancy: many patients recover in adolescence and adulthood

The Natural History of Untreated Primary Hypogammaglobulinemia in Adults: Implications for the Diagnosis and Treatment of Common Variable Immunodeficiency Disorders (CVID)

Chemical chaperones reverse early suppression of regulatory circuits during unfolded protein response in B cells from common variable immunodeficiency patients

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