850 Absence of recurrent bacterial infections in common variable immunodeficiency (CVID): Retention of functional antibody responses despite severe panhypogammaglobulinemia

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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Serum Bactericidal Antibody Responses to Meningococcal Polysaccharide Vaccination as a Basis for Clinical Classification of Common Variable Immunodeficiency

Clinical and Vaccine Immunology ◽

10.1128/cvi.00489-07 ◽

2008 ◽

Vol 15 (4) ◽

pp. 607-611 ◽

Cited By ~ 26

Author(s):

Nima Rezaei ◽

Asghar Aghamohammadi ◽

Seyed Davar Siadat ◽

Mostafa Moin ◽

Zahra Pourpak ◽

...

Keyword(s):

Common Variable Immunodeficiency ◽

Polysaccharide Vaccine ◽

Antibody Responses ◽

Nonresponder Group ◽

Bactericidal Antibody ◽

Recurrent Pyogenic Infections ◽

Normal Controls ◽

Common Variable ◽

Increased Susceptibility

ABSTRACT Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia and increased susceptibility to recurrent pyogenic infections. This study was performed to subclassify CVID on the basis of the bactericidal antibody responses of patients to polysaccharide meningococcal vaccine. Twenty-five patients with CVID (18 male and 7 female) and 25 healthy volunteers received meningococcal polysaccharide vaccine A + C. Serum bactericidal antibody (SBA) titers were measured at baseline and after 3 weeks. Response was correlated with clinical and immunological manifestations of CVID. Twenty-four (96%) of the 25 normal controls had a protective SBA titer of ≥8 postvaccination, whereas only 16 (64%) of the 25 CVID patients had a protective titer (P value = 0.013). Among the patients with CVID who were nonresponders, there were significantly increased rates of bronchiectasis (P = 0.008), splenomegaly (P = 0.016), and autoimmunity (P = 0.034) in comparison with patients who had protective SBA titers. A reversed CD4/CD8 ratio was more common in the nonresponder group of patients (P = 0.053). We conclude that individuals with CVID who cannot produce protective postvaccination titers after receiving meningococcal polysaccharide vaccine are more likely to exhibit bronchiectasis, splenomegaly, and autoimmune diseases. Vaccination response may define subgroups of patients with CVID, enabling more effective monitoring and therapeutic strategies.

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Increased Prevalence of Neoplasms In Patients Diagnosed with Common Variable Immunodeficiency.

Blood ◽

10.1182/blood.v116.21.1531.1531 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1531-1531

Author(s):

William J Grossman ◽

Patrick O Bonnet ◽

Yan Xiong

Keyword(s):

Common Variable Immunodeficiency ◽

Matched Control ◽

Malignant Neoplasm ◽

Antibody Responses ◽

Control Cohort ◽

Diagnosis Code ◽

Hematopoietic Tissue ◽

Increased Risk ◽

Immune Deficiencies ◽

Common Variable

Abstract Abstract 1531 Introduction: Common variable immunodeficiency (CVID) is a heterogenous disorder characterized by hypogammaglobulinemia, poor specific antibody responses, and increased numbers of infections. In addition, patients with CVID have been reported to carry an increased risk of developing other co-morbidities, including autoimmunity and certain types of neoplasms. Data establishing the overall risk and prevalence of these co-morbidities in patients with CVID has been limited due to the small sizes of patient cohorts examined to-date, and the lack of comprehensive primary immunodeficiency registries. The objective of this study was to document the prevalence rates of lymphoma select neoplasms in a large cohort of patients with CVID. Methods: The MedStat MarketScan database, which contains approximately 48 million patients, was evaluated for the number of IVIG-treated CVID patients using the 279.06 ICD-9 code for CVID over a 6-year period (2002-2008). Ten-fold the number of randomly selected patients, based on age, gender and length of enrollment, were used for matched control comparisons to our CVID cohort. Each cohort was evaluated for the rate of select neoplasms using ICD-9 codes for malignant lymphatic and hematopoietic tissue neoplasms (ICD-9 codes 200 to 208). Results: 814 CVID patients with at least 18 months of data were identified in the database, with 61% being female and 39% being male. The average age for females and males was 45 and 37 years, respectively (p<.0001). The CVID cohort carried a significantly higher prevalence of having a diagnosis code for a malignant neoplasm of the lymphatic and hematopoietic tissue than the control cohort [10.1% vs. 0.6%, respectively (p<.0001)]. Most of these neoplasm diagnoses occurred after the diagnosis of their CVID; however, 26.8% of neoplasm diagnoses occurred before the diagnosis of CVID. Additionally, the rates for each of the select neoplasms examined showed a significantly higher rate in the CVID cohort than in the control cohort. Conclusions: This study showed that CIVD patients have a higher prevalence of being co-diagnosed with certain neoplasms than matched controls. These data also suggest that CVID patients should not only be evaluated longitudinally for the development of neoplasms, but that certain cancer patients may also need to be considered and evaluated for underlying immune deficiencies such as CVID. Disclosures: Grossman: Baxter BioScience: Employment. Bonnet:Baxter BioScience: Employment. Xiong:BioScience: Employment.

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Clinical and Immunological Features of 65 Iranian Patients with Common Variable Immunodeficiency

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.7.825-832.2005 ◽

2005 ◽

Vol 12 (7) ◽

pp. 825-832 ◽

Cited By ~ 72

Author(s):

Asghar Aghamohammadi ◽

Abolhasan Farhoudi ◽

Mostafa Moin ◽

Nima Rezaei ◽

Ali Kouhi ◽

...

Keyword(s):

Otitis Media ◽

Common Variable Immunodeficiency ◽

Bacterial Infections ◽

Diagnostic Delay ◽

Primary Immunodeficiency Disease ◽

Serum Immunoglobulin ◽

Recurrent Infections ◽

Baseline Serum ◽

Common Variable

ABSTRACT Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by hypogammaglobulinemia and recurrent bacterial infections. The records of 65 patients with CVID (37 males and 28 females) in the age range of 24 to 537 months were reviewed. By the year 2003, 11 patients had died and seven patients could not be located. The total follow-up period was 221 patient-years. The median diagnostic delay (time between onset and diagnosis) in our patient group was 60 months. At the time of diagnosis, the baseline serum immunoglobulin G (IgG), IgM, and IgA levels were below the level normal for the patients' age; the medians for this group were 120, 10, and 0 mg/dl, respectively. All of the patients presented with infectious diseases at the time of onset, the most common of which were otitis media, diarrhea, pneumonia, and sinusitis. Acute and recurrent infections were also found in almost all of the patients, particularly involving respiratory and gastrointestinal systems. The most common infections, before diagnosis and during follow-up, were pneumonia, acute diarrhea, acute sinusitis, and otitis media. CVID should be considered in any patient with a history of recurrent infections and decreased levels of all serum immunoglobulin isotypes.

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Common variable immunodeficiency syndrome with chronic diarrhoea

BMJ Case Reports ◽

10.1136/bcr-2018-228240 ◽

2019 ◽

Vol 12 (3) ◽

pp. e228240 ◽

Cited By ~ 1

Author(s):

Mukesh Nasa ◽

Smruti Ranjan Mishra ◽

Lipika Lipi ◽

Randhir Sud

Keyword(s):

Common Variable Immunodeficiency ◽

Bacterial Infections ◽

Lymphoid Hyperplasia ◽

Lymphoid Cells ◽

Chronic Diarrhoea ◽

Gi Tract ◽

Chronic Infections ◽

Immunodeficiency Syndrome ◽

Common Variable ◽

Common Variable Immunodeficiency Syndrome

Common variable immunodeficiency syndrome (CVID) is a heterogeneous disorder characterised by diminished levels of IgG, IgA and/or IgM, and recurrent bacterial infections. Sinopulmonary infections are most commonly reported followed by gastrointestinal (GI) infections. GI tract represents the largest immune organ with abundance of lymphoid cells, its involvement can manifest variably ranging from asymptomatic involvement to florid symptoms and signs. Diffuse nodular lymphoid hyperplasia (DNLH) of the GI tract is characterised by numerous small polypoid nodules of variable size in the small intestine, large intestine or both. It is commonly seen in association to immunodeficiency states such as CVID, IgA deficiency and chronic infections due to Giardia lamblia and Helicobacter pylori and cryptosporidiosis. Repetitive antigenic stimulation leads to lymphoid hyperplasia. We herein describe a case of DNLH of the intestine and another case of duodenal cytomegalovirus (CMV) infection associated with CVID.

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Neuroborreliosis in a horse with common variable immunodeficiency

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638718824146 ◽

2019 ◽

Vol 31 (2) ◽

pp. 241-245 ◽

Cited By ~ 2

Author(s):

Heidi L. Pecoraro ◽

M. Julia B. Felippe ◽

Andrew D. Miller ◽

Thomas J. Divers ◽

Kenneth W. Simpson ◽

...

Keyword(s):

Lyme Disease ◽

Common Variable Immunodeficiency ◽

Fluorescent In Situ Hybridization ◽

Bacterial Infections ◽

Rare Condition ◽

Neurologic Disease ◽

Appropriate Therapy ◽

Common Variable ◽

Increased Susceptibility

Common variable immunodeficiency (CVID) is a rare condition in adult horses characterized by hypogammaglobulinemia and increased susceptibility to parasitic and bacterial infections, including recurrent respiratory diseases, septicemia, and meningitis. Lyme disease is often included as a differential diagnosis in CVID horses with signs of meningitis; however, the Borrelia burgdorferi organism has not been demonstrated previously within central nervous system tissues of CVID horses with neurologic disease, to our knowledge. We report herein a case of neuroborreliosis in a CVID horse, confirmed by combined immunologic testing, histopathology, real-time PCR assay, fluorescent in situ hybridization, and immunohistochemical staining. Implications of these findings include heightened monitoring of CVID horses for Lyme disease in endemic areas and appropriate therapy in the case of neurologic disease.

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Common variable immunodeficiency: an important but little-known risk factor for gastric cancer

Revista do Colégio Brasileiro de Cirurgiões ◽

10.1590/0100-6991e-20213133 ◽

2021 ◽

Vol 48 ◽

Author(s):

PAULA KREIN ◽

GUSTAVO GONÇALVES YOGOLARE ◽

MARINA ALESSANDRA PEREIRA ◽

OCTAVIO GRECCO ◽

MYRTHES ANNA MARAGNA TOLEDO BARROS ◽

...

Keyword(s):

Gastric Cancer ◽

Surgical Treatment ◽

Common Variable Immunodeficiency ◽

Bacterial Infections ◽

Disease Recurrence ◽

Clinicopathological Characteristics ◽

Curative Gastrectomy ◽

Significant Difference ◽

Oncological Results ◽

Common Variable

ABSTRACT Introduction: although it is a rare disease, common variable immunodeficiency (CVID) stands out as the most frequent primary symptomatic immunodeficiency. Carriers are prone to a variety of recurrent bacterial infections, in addition to the risk of developing autoimmune diseases and neoplasms including gastric cancer (GC). Despite the recognized risk, there are no specific standardized protocols for the management of GC in these patients, so the reported oncological results are varied. Thus, this study aims to describe the clinicopathological characteristics and prognosis of patients with CVID undergoing surgical treatment of GC. Methods: all patients with GC undergoing surgical treatment between 2009 and 2020 were retrospectively evaluated. Later, patients diagnosed with CVID were identified and this group was compared with the remaining patients without any immunodeficiency. Results: among the 1101 patients with GC evaluated in the period, 10 had some type of immunodeficiency, and 5 were diagnosed with CVID. Patients with CVID had younger age, lower BMI, and smaller lesions compared to those without CVID. Four patients underwent curative gastrectomy and one patient underwent jejunostomy. Two patients died (1 palliative and 1 curative) and one patient had disease recurrence. There was no statistically significant difference regarding the incidence of postoperative complications and survival between the evaluated groups. Conclusion: the CVID incidence in patients with GC undergoing surgical treatment was 0.5%, occurring at a less advanced age, but with no difference regarding surgical and oncological results.

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