The pediatric common variable immunodeficiency — from genetics to therapy: a review

AbstractCommon variable immunodeficiency (CVID) is the most prevalent antibody deficiency, characterized by remarkable genetic, immunological, and clinical heterogeneity. The diagnosis of pediatric CVID is challenging due to the immaturity of the immune response and sustained actively developing antibody affinity to antigens and immunological memory that may overlap with the inborn error of immunity. Significant progress has been recently done in the field of immunogenetics, yet a paucity of experimental and clinical studies on different systemic manifestations and immunological features of CVID in children may contribute to a delayed diagnosis and therapy. In this review, we aimed at defining the variable epidemiological, etiological, and clinical aspects of pediatric CVID with special emphasis on predominating infectious and non-infectious phenotypes in affected children.Conclusion: While pediatric CVID is a multifaceted and notorious disease, increasing the pediatricians’ awareness of this disease entity and preventing the diagnostic and therapeutic delay are needed, thereby improving the prognosis and survival of pediatric CVID patients. What is Known:• CVID is an umbrella diagnosis characterized by complex pathophysiology with an antibody deficiency as a common denominator.• It is a multifaceted disease characterized by marked genetic, immunological, and clinical heterogeneity.. What is New:• The diagnosis of pediatric CVID is challenging due to the immaturity of innate and adaptive immune response.• Increasing the pediatricians’ awareness of CVID for the early disease recognition, timely therapeutic intervention, and improving the prognosis is needed.

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Cellular and humoral influenza-specific immune response upon vaccination in patients with common variable immunodeficiency and unclassified antibody deficiency

Vaccine ◽

10.1016/j.vaccine.2016.03.091 ◽

2016 ◽

Vol 34 (21) ◽

pp. 2417-2423 ◽

Cited By ~ 17

Author(s):

Leif G. Hanitsch ◽

Madlen Löbel ◽

Jan Florian Mieves ◽

Sandra Bauer ◽

Nina Babel ◽

...

Keyword(s):

Immune Response ◽

Common Variable Immunodeficiency ◽

Antibody Deficiency ◽

Specific Immune Response ◽

Common Variable

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Common variable immunodeficiency disorder associated with bronchiectasis: a case report

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20210665 ◽

2021 ◽

Vol 8 (3) ◽

pp. 565

Author(s):

Mohammad Zahirul Islam Khan ◽

Kamrul Laila ◽

Mohammed Mahbubul Islam ◽

Mohammad Imnul Islam ◽

Shahana Akhter Rahman

Keyword(s):

Health Care Providers ◽

Common Variable Immunodeficiency ◽

Delayed Diagnosis ◽

Gene Mutations ◽

Growth Failure ◽

Recurrent Infections ◽

Care Providers ◽

Immunodeficiency Disorder ◽

Specific Antibody Production ◽

Common Variable

Common variable immunodeficiency disorder (CVID) is the commonest type of primary immunodeficiency disorders (PIDs) characterized by hypogammaglobulinemia, defective specific antibody production and increased susceptibility of recurrent infections. Autoimmunity, neoplasm and lymphoproliferative disorders are usually associated with CVID. In most cases, the cause is unknown, but multiple gene mutations (10%) may be associated with CVID. Here, we report an eight years old girl with CVID presented with recurrent infections, growth failure, generalized lymphadenopathy and hepatosplenomegaly. Chest examination and radiological findings of this girl were consistent with bronchiectasis. Lack of awareness among health care providers is the reason for delayed diagnosis of several years for this girl. Therefore, it is essential to raise awareness regarding PID patients among the physicians to improve the quality of life.

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Delayed diagnosis in common variable immunodeficiency

The Journal of Pediatrics ◽

10.1016/j.jpeds.2009.04.019 ◽

2009 ◽

Vol 154 (6) ◽

pp. A1 ◽

Cited By ~ 1

Author(s):

Robert W. Wilmott

Keyword(s):

Common Variable Immunodeficiency ◽

Delayed Diagnosis ◽

Common Variable

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Clinical and laboratory characteristics of clozapine-treated patients with schizophrenia referred to a national immunodeficiency clinic reveals a B-cell signature resembling common variable immunodeficiency (CVID)

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-206235 ◽

2020 ◽

Vol 73 (9) ◽

pp. 587-592 ◽

Cited By ~ 5

Author(s):

Mark James Ponsford ◽

Rachael Steven ◽

Kathyrn Bramhall ◽

Mathew Burgess ◽

Sonali Wijetilleka ◽

...

Keyword(s):

Common Variable Immunodeficiency ◽

Antibody Deficiency ◽

Case Note ◽

Retrospective Case ◽

Clozapine Therapy ◽

Clozapine Treatment ◽

Immunoglobulin Replacement ◽

Common Variable ◽

Case Note Review ◽

Drug Cessation

AimsAn association between antibody deficiency and clozapine use in individuals with schizophrenia has recently been reported. We hypothesised that if clozapine-associated hypogammaglobulinaemia was clinically relevant this would manifest in referral patterns.MethodsRetrospective case note review of patients referred and assessed by Immunology Centre for Wales (ICW) between January 2005 and July 2018 with extraction of clinical and immunological features for individuals with diagnosis of schizophrenia-like illness.Results1791 adult patients were assessed at ICW during this period; 23 patients had a psychiatric diagnosis of schizophrenia or schizoaffective disorder. Principal indications for referral were findings of low calculated globulin and immunoglobulins. Clozapine was the single most commonly prescribed antipsychotic (17/23), disproportionately increased relative to reported use in the general schizophrenia population (OR 6.48, 95% CI: 1.79 to 23.5). Clozapine therapy was noted in 6/7 (86%) of patients subsequently requiring immunoglobulin replacement therapy (IgRT). Marked reduction of class-switched memory B cells (CSMB) and plasmablasts were observed in clozapine-treated individuals relative to healthy age-matched controls. Clozapine duration is associated with CSMB decline. One patient discontinued clozapine, with gradual recovery of IgG levels without use of IgRT.ConclusionsOur findings are consistent with enrichment of clozapine-treatment within schizophrenic individuals referred for ICW assessment over the last 13 years. These individuals displayed clinical patterns closely resembling the primary immunodeficiency common variable immunodeficiency, however appears reversible on drug cessation. This has diagnostic, monitoring and treatment implications for psychiatry and immunology teams and directs prospective studies to address causality and the wider implications for this patient group.

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