Non-infectious Complications of Common Variable Immunodeficiency: Updated Clinical Spectrum, Sequelae, and Insights to Pathogenesis

Common variable immunodeficiency (CVID) is a heterogenous group of immunologic disorders of unknown etiology. Alterations of the normal cellular balance due to an increase in reactive oxygen species and/or decrease in antioxidant defense may lead to increased oxidative stress. We aimed to evaluate the levels of oxidative stress biomarkers in patients with CVID who had different presentations. We investigated the serum catalase (CAT), erythrocyte superoxide dismutase (SOD), erythrocyte reduced glutathione as antioxidants and serum malondialdehyde levels as lipid peroxidation marker in patients with CVID in Uludag University Hospital Department of Pediatric Allergy and Immunology’s outpatient clinics. In the analysis, there were 21 patients and 27 matched healthy controls. The median levels of CAT in patients with CVID was significantly lower than in healthy controls ( p = 0.04). Among the patients with CVID, 19% had autoimmune disease, one had Sjögren’s syndrome, one had autoimmune alopecia, one had juvenile rheumatoid arthritis, and one had chronic inflammatory demyelinating polyneuropathy. Patients with autoimmune complications had significantly lower CAT levels compared to the ones without autoimmune diseases ( p = 0.03). The patients without non-infectious complications (NICs) had lower SOD levels than the patients with NICs ( p = 0.05). The analysis of oxidative stress markers in the patients with CVID suggested a series of abnormalities in the anti-oxidant system. The clinical syndrome associations may be a useful tool for future studies to set prediction markers for the prognosis of patients with CVID.

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Granulomatous lymphocytic interstitial lung disease as a complication of common variable immunodeficiency

Russian Pulmonology ◽

10.18093/0869-0189-2021-31-6-816-821 ◽

2021 ◽

Vol 31 (6) ◽

pp. 816-821

Author(s):

Alexandr V. Averyanov ◽

Anastasia S. Perkina

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Common Variable Immunodeficiency ◽

Clinical Case ◽

Infectious Complications ◽

Pathological Process ◽

Malignant Neoplasms ◽

Recurrent Infections ◽

Autoimmune Conditions ◽

Common Variable

Common variable immunodeficiency (CVID) is a rare immunodeficiency, the classic manifestation being recurrent infections. Other lesions are often found in CVID patients, such as malignant neoplasms, autoimmune conditions caused by abnormal cellular immunity, in addition to infectious complications. Usually, the pathological process involves the lungs. This article presents a clinical case of a patient with CVID complicated by granulomatous lymphocytic interstitial lung disease.

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Involvement of miR-142 and miR-155 in Non-Infectious Complications of CVID

Molecules ◽

10.3390/molecules25204760 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4760

Author(s):

Giuliana Amato ◽

Federica Vita ◽

Paolina Quattrocchi ◽

Paola Lucia Minciullo ◽

Giovanni Pioggia ◽

...

Keyword(s):

Common Variable Immunodeficiency ◽

Bacterial Infections ◽

Infectious Complications ◽

Knock Out ◽

Scientific Databases ◽

Clinical Complications ◽

Mesh Terms ◽

Bibliographic Search ◽

Epigenetic Phenomenon ◽

Common Variable

Background and objectives: Common variable immunodeficiency (CVID) is the most prevalent antibody impairment. It is characterized by failure in immunoglobulin and protective antibody generation and defined by an increased tendency toward bacterial infections, autoimmunity, and malignancy. Most CVID diagnoses do not follow a classical Mendelian pattern of inheritance. In recent years, CVID has been considered an epigenetic phenomenon in the majority of cases, overtaking previous monogenetic and/or polygenetic theories. The aim of this study was to review the role of microRNAs (miRNAs) in CVID, focusing on the involvement of the same miRNAs in various non-infectious clinical complications of CVID, mainly autoimmunity and/or cancer. Materials and Methods: A bibliographic search of the scientific literature was carried out independently by two researchers in scientific databases and search engines. The MeSH terms “microRNAs” and “common variable immunodeficiency” were used. All research articles from inception to May 2020 were considered. Results: The literature data showed the involvement of two miRNAs in primary immunodeficiency: miR-142 and miR-155. Both of these miRNAs have been investigated through mice models, in which miR-142 and miR-155 were deleted. These knock-out (KO) mice models showed phenotypic analogies to CVID patients with hypogammaglobulinemia, adaptive immunodeficiency, polyclonal proliferation, lung disease, and enteric inflammation. miR-142 and miR-155 have been found to be involved in the following autoimmune and neoplastic clinical complications of CVID: Gastric cancer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, natural killer/Tcell lymphoma (NKTCL), and immune thrombocytopenia. Conclusions: miR-142 and miR-155 deregulation leads to similar CVID phenotypesin KO mice models. Although no data are available on the involvement of these miRNAs in human CVID, their dysregulation has been detected in human CVID comorbidities. The literature data show that miRNA sequences in murine models are comparable to those in humans; therefore, miR-142 and miR-155 involvement in human CVID could be hypothesized.

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Case Report of Heart Transplantation for Giant Cell Myocarditis in a Patient with Common Variable Immunodeficiency

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytab447 ◽

2021 ◽

Author(s):

Thomas A Franzon ◽

Anna Kovalszki ◽

Raja Rabah ◽

John M Nicklas

Keyword(s):

Heart Transplantation ◽

Giant Cell ◽

Organ Transplantation ◽

Common Variable Immunodeficiency ◽

Solid Organ Transplantation ◽

Infectious Complications ◽

Solid Organ ◽

Giant Cell Myocarditis ◽

Common Variable

Abstract Background Solid organ transplantation in patients with common variable immunodeficiency (CVID) is controversial due to the risk for severe and recurrent infections. Determining transplantation candidacy in CVID patients is further complicated by the presence of CVID-related noninfectious complications that can reduce overall survival and also recur in the transplanted organ. Data regarding solid organ transplantation in patients with CVID is limited, particularly in heart transplantation. Case Summary A 32 year-old female with CVID presented with new heart failure after 3 months of dyspnea on exertion. Her echocardiogram showed severe global systolic dysfunction with an ejection fraction of approximately 10%, and her right heart catheterization revealed severe biventricular pressure overload and severely reduced cardiac output. Endomyocardial biopsy revealed giant cells and mononuclear infiltrate consistent with giant cell myocarditis. Despite medical management, she developed progressive cardiogenic shock and underwent uncomplicated orthotopic heart transplantation on hospital day 38. After two years of follow up, she has had no major infectious complications and continues to have normal graft function with no recurrence of giant cell myocarditis. Conclusion We report a case of successful heart transplantation for giant cell myocarditis in a patient with CVID, with no major infectious complications after 2 years of follow up. CVID should not be considered an absolute contraindication for heart transplantation.

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