Respiratory Infections and Antibiotic Usage in Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) belongs to the primary immunodeficiency disorders (PIDs), presenting a profound heterogeneity in phenotype and genotype, with monogenic or complex causes. Recurrent respiratory infections are the most common clinical manifestations. CVID patients can also develop various autoimmune and lymphoproliferative complications. Genetic testing such as whole exome sequencing (WES) can be utilized to investigate likely genetic defects, helping for better clinical management. We described the clinical phenotypes of three sporadic cases of CVID, who developed recurrent respiratory infections with different autoimmune and lymphoproliferative complications. WES was applied to screen disease-causing or disease-associated mutations. Two patients were identified to have monogenic disorders, with compound heterozygous mutations in LRBA for one patient and a frameshift insertion in NFKB1 for another. The third patient was identified to be a complex form of CVID. Two novel mutations were identified, respectively, in LRBA and NFKB1. A combination of clinical and genetic diagnosis can be more extensively utilized in the clinical practice due to the complexity and heterogeneity of CVID.

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Vitamin D Levels and Respiratory Infections in Patients with Common Variable Immunodeficiency

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2011.12.649 ◽

2012 ◽

Vol 129 (2) ◽

pp. AB86 ◽

Cited By ~ 1

Author(s):

J. Zheng ◽

K. Gundling

Keyword(s):

Vitamin D ◽

Common Variable Immunodeficiency ◽

Respiratory Infections ◽

Vitamin D Levels ◽

Common Variable

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The Central Nervous System Effects and Mimicry of Common Variable Immunodeficiency (CVID): A Case Report with Literature Review

Case Reports in Rheumatology ◽

10.1155/2019/7623643 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Sohail Farshad ◽

Fernando Figueroa Rodriguez ◽

Alexandra Halalau ◽

Joseph Skender ◽

Cory Rasmussen ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Literature Review ◽

Common Variable Immunodeficiency ◽

Respiratory Infections ◽

Neurological Complications ◽

Treatment Team ◽

Treatment Regimens ◽

The Central Nervous System ◽

Common Variable

There is a scarceness of information on the central nervous system effects of common variable immunodeficiency (CVID). A 30-year-old woman with a history of recurrent upper respiratory infections, vitiligo, and immune thrombocytopenic purpura presented with right-sided numbness. Magnetic resonance imaging (MRI) of the thoracic spine revealed a signal hyperintensity. MRI of the brain demonstrated FLAIR hyperintensity in the right middle frontal gyrus. Cerebral spinal fluid was unremarkable. Serum immunoglobulins revealed hypogammaglobulinemia. Endobronchial and subsequent mediastinum biopsies were all negative for sarcoidosis and malignancy. No infectious etiology was found. She was treated with glucocorticoids and intravenous immunoglobulin (IVIG) replacement therapy for CVID-associated myelitis. Follow-up MRI showed improvement; however, her numbness persisted despite these treatments, which led to an outside physician adding methotrexate for their suspicion of sarcoidosis. Her symptoms remained stable for two years, but when the methotrexate dose was weaned, her numbness worsened. Upon review, the treatment team refuted the diagnosis of sarcoidosis but continued treatment with prednisone, IVIG, and methotrexate for CVID-associated myelitis, from which her symptoms have stabilized. Here, we discuss CVID-associated neurological complications, its similarities to sarcoidosis, and a literature review with treatment regimens and outcomes.

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Trained Immunity Based-Vaccines as a Prophylactic Strategy in Common Variable Immunodeficiency. A Proof of Concept Study

Biomedicines ◽

10.3390/biomedicines8070203 ◽

2020 ◽

Vol 8 (7) ◽

pp. 203

Author(s):

Kissy Guevara-Hoyer ◽

Paula Saz-Leal ◽

Carmen M. Diez-Rivero ◽

Juliana Ochoa-Grullón ◽

Miguel Fernández-Arquero ◽

...

Keyword(s):

Common Variable Immunodeficiency ◽

Respiratory Infections ◽

Pharmacoeconomic Analysis ◽

Indirect Costs ◽

Antibiotic Use ◽

Sublingual Administration ◽

Trained Immunity ◽

Before And After ◽

Tract Infections ◽

Common Variable

Background. A major concern in the care of common variable immunodeficiency (CVID) patients is the persistence of subclinical or recurrent respiratory tract infections (RRTI) despite adequate trough IgG levels, which impacts the quality of life (QoL) and morbidity. Therefore, the development of new approaches to prevent and treat infection, especially RRTI, is necessary. Objectives. We conducted a clinical observational study from May, 2016 to December, 2017 in 20 CVID patients; ten of these patients had a history of RRTI and received the polybacterial preparation MV130, a trained immunity-based vaccine (TIbV) to assess its impact on their QoL and prognosis. Methods. Subjects with RRTI received MV130 for 3 months and were followed up to 12 months after initiation of the treatment. The primary endpoint was a reduction in RRTI at the end of the study. We analyzed the pharmacoeconomic impact on the RRTI group before and after immunotherapy by estimating the direct and indirect costs, and assessed CVID-QoL and cytokine profile. Specific antibody responses to the bacteria contained in MV130 were measured. Results. The RRTI-group treated with TIbV MV130 showed a significant decrease in infection rate (p = 0.006) throughout the 12 months after initiation of the treatment. A decrease in antibiotic use and unscheduled outpatient visits was observed (p = 0.005 and p = 0.002, respectively). Significant increases in anti-pneumococcus and anti-MV130 IgA antibodies (p = 0.039 both) were detected after 12 months of MV130. Regarding the CVID QoL questionnaire, an overall decrease in the score by more than 50% was observed (p < 0.05) which demonstrated that patients experienced an improvement in their QoL. The pharmacoeconomic analysis showed that the real annual direct costs decreased up to 4 times per patient with the prophylactic intervention (p = 0.005). Conclusion. The sublingual administration of the TIbV MV130 significantly reduced the rate of respiratory infections, antibiotic use and unscheduled visits, while increasing specific IgA responses in CVID patients. Additionally, the CVID population felt that their QoL was improved, and a decrease in expenses derived from health care was predicted.

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1316. Uncommon Presentations of Common Variable Immunodeficiency

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1508 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S746-S747

Author(s):

Akankcha Alok ◽

John Greene ◽

Sadaf Aslam

Keyword(s):

T Cell ◽

Mycobacterium Avium ◽

Common Variable Immunodeficiency ◽

Streptococcus Agalactiae ◽

Mycobacterium Avium Complex ◽

Respiratory Infections ◽

Immunoglobulin M ◽

Lymphocyte Function ◽

Lung Infections ◽

Common Variable

Abstract Background Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder which affects B lymphocyte function and differentiation causing decreased levels of Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin M (IgM).1 The objective of this study is to highlight how hypogammaglobulinemia can lead to respiratory infections with microbes that are lesser known in the background of CVID with the help of a two-case series. Methods Medical records of two patients with CVID were reviewed who were found to have mycobacterium avium-complex intracellulare and streptococcus agalactiae lung infections respectively. Results Decreased IgG in CVID means reduced antibody production, low IgA leads to mucosal inflammation and increased susceptibility to respiratory infections2 and lower IgM memory B-cells causes infections with encapsulated microorganisms.3 Table 1 highlights the various respiratory infections and their etiologies that have been reported with CVID, the most common being encapsulated organisms like Haemophilus influenza, Streptococcus pneumonia, Neisseria meningitidis along with enterovirus. Table 2 demonstrates our findings. In the first case we have reported a patient with mycobacterium avium-complex intracellulare (MAC-I). This could be because of hypogammaglobulinemia, decreased B and T-cell interaction and reduced T-cell signaling caused by CVID.4 Although, mycobacterium tuberculosis, simiae and hominis lung infections and mycobacterium bovis systemic infections have been reported before, MAC-I is relatively rare in CVID.5 In our second case, the patient developed streptococcus agalactiae or Group-B streptococcus (GBS) empyema. Most cases of GBS have been reported in pregnant women and infants. Infections with other encapsulated organisms have been reported in CVID but GBS empyema is less frequent and can happen due to decreased bacteria-specific CD4 cells, microbial translocation and hypogammaglobulinemia.6 . Table 1. Respiratory Infections reported in CVID along with their etiologies. Figure 1. CT image of MAC-I infection. Conclusion We encountered two unique cases of CVID with rare infectious etiologies. The cases are intended to create an awareness and vigilance regarding CVID induced hypogammaglobulinemia which can cause respiratory infections with lesser known pathogens where antibodies may be important. Disclosures All Authors: No reported disclosures

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Alterations of the X-linked lymphoproliferative disease geneSH2D1A in common variable immunodeficiency syndrome

Blood ◽

10.1182/blood.v98.5.1321 ◽

2001 ◽

Vol 98 (5) ◽

pp. 1321-1325 ◽

Cited By ~ 85

Author(s):

Massimo Morra ◽

Olin Silander ◽

Silvia Calpe ◽

Michelle Choi ◽

Hans Oettgen ◽

...

Keyword(s):

Common Variable Immunodeficiency ◽

B Lymphocyte ◽

Respiratory Infections ◽

Immunoglobulin A ◽

Elevated Serum ◽

B Cell Lymphoma ◽

Lymphoproliferative Disease ◽

Susceptibility To Infection ◽

Immunoglobulin Deficiency ◽

Common Variable

X-linked lymphoproliferative (XLP) disease is a primary immunodeficiency caused by a defect in the SH2D1A gene. At least 3 major manifestations characterize its clinical presentation: fatal infectious mononucleosis (FIM), lymphomas, and immunoglobulin deficiencies. Common variable immunodeficiency (CVID) is a syndrome characterized by immunoglobulin deficiency leading to susceptibility to infection. In some patients with CVID, a defective btk orCD40-L gene has been found, but most often there is no clearly identified etiology. Here, 2 unrelated families in whom male members were affected by CVID were examined for a defect in theXLP gene. In one family previously reported in the literature as having progressive immunoglobulin deficiencies, 3 brothers were examined for recurrent respiratory infections, whereas female family members showed only elevated serum immunoglobulin A levels. A grandson of one of the brothers died of a severeAspergillus infection secondary to progressive immunoglobulin deficiency, FIM, aplastic anemia, and B-cell lymphoma. In the second family, 2 brothers had B lymphocytopenia and immunoglobulin deficiencies. X-linked agammaglobulinemia syndrome was excluded genetically, and they were classified as having CVID. The occurrence of FIM in a male cousin of the brothers led to the XLP diagnosis. Because the SH2D1A gene was found altered in both families, these findings indicate that XLP must be considered when more than one male patient with CVID is encountered in the same family, and SH2D1A must be analyzed in all male patients with CVID. Moreover, these data link defects in the SH2D1A gene to abnormal B-lymphocyte development and to dysgammaglobulinemia in female members of families with XLP disease.

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