Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

Baldovino, Simone; Montin, Davide; Martino, Silvana; Sciascia, Savino; Menegatti, Elisa; Roccatello, Dario

doi:10.1016/j.autrev.2012.11.003

Cited by 51 publications

(28 citation statements)

References 73 publications

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“…While mutations autosomal genes leading to loss of B cell function have been identified in a few rare cases [4], [5,6,7][8,9],, for the great majority of patients, the genetic basis remains unknown. As for other predominantly B cell defects, immunoglobulin (Ig) replacement is the mainstay of treatment, and while this therapy effectively reduces the incidence of bacterial infections, it does not prevent or ameliorate the non-infectious organ-damaging complications which develop in about half of all subjects [10,11]. These complications include hematologic and organ-specific autoimmunity, granulomatous infiltrations, interstitial lung disease, lymphoid hyperplasia, gastrointestinal inflammatory disease, cancer, and lymphoma [12,13,14,15,16].…”

Section: Introductionmentioning

confidence: 99%

Interferon Signature in the Blood in Inflammatory Common Variable Immune Deficiency

Park

Munagala²,

et al. 2013

PLoS ONE

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About half of all subjects with common variable immune deficiency (CVID) are afflicted with inflammatory complications including hematologic autoimmunity, granulomatous infiltrations, interstitial lung disease, lymphoid hyperplasia and/or gastrointestinal inflammatory disease. The pathogenesis of these conditions is poorly understood but singly and in aggregate, these lead to significantly increased (11 fold) morbidity and mortality, not experienced by CVID subjects without these complications. To explore the dysregulated networks in these subjects, we applied whole blood transcriptional profiling to 91 CVID subjects, 47 with inflammatory conditions and 44 without, in comparison to subjects with XLA and healthy controls. As compared to other CVID subjects, males with XLA or healthy controls, the signature of CVID subjects with inflammatory complications was distinguished by a marked up-regulation of IFN responsive genes. Chronic up-regulation of IFN pathways is known to occur in autoimmune disease due to activation of TLRs and other still unclarified cytoplasmic sensors. As subjects with inflammatory complications were also more likely to be lymphopenic, have reduced B cell numbers, and a greater reduction of B, T and plasma cell networks, we suggest that more impaired adaptive immunity in these subjects may lead to chronic activation of innate IFN pathways in response to environmental antigens. The unbiased use of whole blood transcriptome analysis may provides a tool for distinguishing CVID subjects who are at risk for increased morbidity and earlier mortality. As more effective therapeutic options are developed, whole blood transcriptome analyses could also provide an efficient means of monitoring the effects of treatment of the inflammatory phenotype.

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Section: Introductionmentioning

confidence: 99%

Interferon Signature in the Blood in Inflammatory Common Variable Immune Deficiency

Park

Munagala²,

et al. 2013

PLoS ONE

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“…Autoimmune diseases can occur with increased frequency in CVID [2][3][4]. Pathogenesis of autoimmunity is unknown in CVID patients, although a loss of switched memory B cells, defective elimination of autoimmune B cells and T cell dysfunction have been implicated [10].…”

Section: Discussionmentioning

confidence: 99%

“…Typically, patients present with recurrent bacterial infections of the respiratory and gastrointestinal tract. They may also develop malignancies, inflammatory and autoimmune complications [2][3][4]. The depletion of switched memory B cells as well as attenuation of regulatory T cells have been shown to be associated with autoimmune disease in patients with CVID [5].…”

Section: Introductionmentioning

confidence: 99%

Juvenile Idiopathic Arthritis (JIA) Presenting as Temporomandibular Joint Arthritis in Patients with Common Variable Immunodeficiency (CVID)

Jolanta¹,

Finn²

2015

Pediat Therapeut

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CVID is the most common clinically encountered primary antibody deficiency disorder and can be associated with autoimmune complications. We report 2 children with CVID who developed joint symptoms several years after initial diagnosis and were referred to a pediatric rheumatologist, who suspected temporomandibular joint arthritis clinically. Both patients underwent MRI imaging with contrast administration, which confirmed temporomandibular arthritis. They were successfully treated with intra-articular steroid joint injections. Juvenile idiopathic arthritis (JIA) can be one of the autoimmune associations with CVID, but temporomandibular arthritis as the primary manifestation is uncommon, difficult to detect clinically and has not been described previously in CVID. Although jaw pain and discomfort on chewing might indicate underlying temporomandibular joint arthritis, these symptoms might not necessarily be present. If not promptly identified and treated, arthritis of JIA can cause joint damage/disability and therefore needs specialist multidisciplinary management under a pediatric rheumatologist. JIA may not respond to steroid injections alone and might require escalation in therapy with systemic immunosuppressive agents. Little is known about the intricacies of systemic immunosuppressive therapy in patients with CVID who develop JIA. Conclusion:In relation to CVID, juvenile idiopathic arthritis (JIA) can be an associated autoimmune manifestation. JIA presenting as temporomandibular joint arthritis as the first manifestation is unusual but can occur and might be potentially difficult to detect clinically. Pediatricians should be aware of the possibility of JIA in a child with CVID and refer to a pediatric rheumatologist for appropriate management. If not treated promptly, JIA can cause joint destruction and disability.

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“…More than 25% of CVID patients have been reported to have autoimmune complications. 23 Autoantibodies and auto-reactive B cells can be detected in these patients, even if serum immunoglobulins are very low and specific response to various antigens is impaired. 24 Cytopenia is the most common autoimmune manifestation in these patients with CVID 25 and autoimmune thrombocytopenia (ITP) was found in 7 out of 18 patients in our study.…”

Section: Volume 59 • Number 5 Infection Profiles Of Turkish Patientsmentioning

confidence: 99%

Defective pneumococcal antibody response in patients with recurrent respiratory tract infections

Erman¹,

Demirtaş

Bildik

et al. 2017

Turk J Pediatr

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Streptococcus pneumoniae is a common pathogen responsible for pulmonary infections and the leading cause of mortality and morbidity in patients with particularly B cell immunodeficiencies. Antibody production is the principal protective immune response against S. pneumoniae and measurement of the production of antipolysaccharide antibodies is important in the evaluation of B cell deficiencies. We quantified serotype-specific immunoglobulin G antibodies against seven common pneumococcal serotypes before and three weeks after unconjugated vaccine in 416 patients with recurrent respiratory tract infections; fifty-five (13%) of whom showed impaired antibody response. We could evaluate 41 of these 55 patients for their particular clinical features. Specific antibody deficiency, was diagnosed in 10 of these patients, common variable immunodeficiency in 18, ataxia telangiectasia in 10 and other antibody deficiencies in 7 (transient hypogammaglobulinemia in 4, IgG subclass deficiency in 1, partial and selective IgA deficiency in 1) patients. Evaluation of the antibody response to polysaccharide antigens should be considered early on in patients with recurrent respiratory infections and required particularly for the diagnosis of specific antibody deficiency and the decision of the appropriate treatment approaches.

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Common variable immunodeficiency: Crossroads between infections, inflammation and autoimmunity

Cited by 51 publications

References 73 publications

Interferon Signature in the Blood in Inflammatory Common Variable Immune Deficiency

Interferon Signature in the Blood in Inflammatory Common Variable Immune Deficiency

Juvenile Idiopathic Arthritis (JIA) Presenting as Temporomandibular Joint Arthritis in Patients with Common Variable Immunodeficiency (CVID)

Defective pneumococcal antibody response in patients with recurrent respiratory tract infections

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