Combined immunodeficiency and Epstein-Barr virus–induced B cell malignancy in humans with inherited CD70 deficiency

Abolhassani, Hassan; Edwards, Emily S.J.; İkincioğulları, Aydan; Jing, Huie; Borte, Stephan; Buggert, Marcus; Du, Likun; Matsuda-Lennikov, Mami; Romano, Rosa; Caridha, Rozina; Bade, Sangeeta; Zhang, Yu; Frederiksen, Juliet; Fang, Mingyan; Bal, Sevgi Köstel; Haskoloğlu, Şule; Doğu, Figen; Taçyıldız, Nurdan; Matthews, Helen; McElwee, Joshua; Gostick, Emma; Price, David A.; Palendira, Umaimainthan; Aghamohammadi, Asghar; Boisson, Bertrand; Rezaei, Nima; Karlsson, Annika C.; Lenardo, Michael J.; Casanova, Jean‐Laurent; Hammarström, Lennart; Tangye, Stuart G.; Su, Helen C.; Pan‐Hammarström, Qiang

doi:10.1084/jem.20160849

Cited by 129 publications

(124 citation statements)

References 56 publications

(82 reference statements)

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“…GLILD (usually presenting in CVID), chronic granulomatous disease, and immune dysregulation (including hemophagocytic lymphohistiocytosis and autoimmune lymphoproliferative syndrome) are common lymphoproliferative PIDs associated with pulmonary adenopathies. Primary lymphoma (extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue due to increased genetic vulnerability to Epstein-Barr virus-induced complications) [120,121] and secondary lung metastatic malignancy (in PAD and CID patients with DNA repair system defects, NK-cell defects, and cytotoxic T-cell defects) may present initially with thoracic adenopathy [122][123][124]. Infiltration of the lung with metastases and subsequent restrictive disease is more common than primary lung tumors.…”

Section: Pulmonary Adenopathies and Malignanciesmentioning

confidence: 99%

Infectious and Noninfectious Pulmonary Complications in Patients With Primary Immunodeficiency Disorders

Yazdani

Abolhassani

et al. 2017

J Investig Allergol Clin Immunol

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Primary immunodeficiency disorders (PIDs) are caused by 1 or more defects of the immune system. Patients are more likely to experience recurrent and/or severe infections and tend to develop a wide range of complications. Respiratory diseases are the main and initial manifestation in most cases and the most common complication. Pulmonary complications cause significant morbidity and mortality in patients with PIDs. Early diagnosis and appropriate treatment can prevent or at least slow the development of respiratory complications. Since the spectrum of pulmonary complications in PIDs is broad, we divided pulmonary complications into upper respiratory complications (eg, sinusitis, otitis media, and laryngeal angioedema) and lower respiratory complications (eg, pneumonia, bronchitis, bronchiectasis, interstitial lung diseases, organizing pneumonia, pulmonary adenopathies and malignancies, hyperreactive airway diseases, pulmonary dysgenesis, and adverse reactions to treatment). This review covers the main respiratory manifestations in patients with PIDs. Key words: Primary immunodeficiency disorders. Pulmonary complications. Upper respiratory tract. Lower respiratory tract. ResumenLas inmunodeficiencias primarias (PIDs) son enfermedades causadas por uno o más defectos del sistema inmunológico. Estos pacientes presentan con frecuencia infecciones recidivantes y/o severas así como otro tipo de complicaciones. Las patologías respiratorias son la principal y más frecuente manifestación y complicación de las PIDs. Las complicaciones de estas patologías pulmonares constituyen una de las principales causas de morbimortalidad entre los pacientes que sufren PIDs. El diagnóstico temprano y el tratamiento adecuado pueden prevenir, o al menos retrasar, la aparición de las complicaciones respiratorias en estos pacientes. Dado que el espectro de las enfermedades pulmonares es muy amplio, hemos dividido estas complicaciones entre aquellas que afectan a las vías aéreas superiores (sinusitis, otitis media y angioedema laríngeo, etc.) y las que afectan a las vías aéreas bajas (neumonía, bronquitis, bronquiectasias, enfermedades pulmonares intersticiales, neumonía organizada, adenopatías pulmonares y neoplasias, hiperreactividad bronquial, disgenesia pulmonar y las debidas a los efectos secundarios del tratamiento instaurado). Este artículo revisa las manifestaciones respiratorias que se observan más frecuentemente en los pacientes con PIDs. Palabras clave: Inmunodeficiencias primarias. Complicaciones pulmonares. Vías respiratorias altas. Vías respiratorias bajas.

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Section: Pulmonary Adenopathies and Malignanciesmentioning

confidence: 99%

Infectious and Noninfectious Pulmonary Complications in Patients With Primary Immunodeficiency Disorders

Yazdani

Abolhassani

et al. 2017

J Investig Allergol Clin Immunol

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“…For instance, both genetic lesions affecting immune response and certain immunosuppressants are associated with increased risk of EBV lymphoproliferative disease. [4][5][6] These EBV-associated hematolymphoid tumors often respond to immune interventions such as adoptive cellular therapy with EBV-specific T cells or withdrawal of immunosuppressive pharmacologic agents. 7 Immune dysfunction as a predisposing factor is poorly defined in EBV 1 tumors not associated with overt systemic immunosuppression, including CHL, nasopharyngeal carcinoma, and gastric carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Th17 immune microenvironment in Epstein-Barr virus–negative Hodgkin lymphoma: implications for immunotherapy

et al. 2017

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Key Points• CHL broadly expresses the PD-1/PD-L1 pathway, but EBV 1 CHL displays a Th1 profile, whereas EBV 2 tumors have a pathogenic Th17 profile.• These findings support further studies to define the role of the IL-23/IL-17 axis in CHL response/resistance to anti-PD-1 therapy.Classical Hodgkin lymphoma (CHL) is a neoplasm characterized by robust inflammatory infiltrates and heightened expression of the immunosuppressive PD-1/PD-L1 pathway.Although anti-PD-1 therapy can be effective in .60% of patients with refractory CHL,

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“…CD70-CD27 interaction provides a potent second signal for CD4 T cell-dependent and -independent CD8 T cell priming, effector differentiation, and memory development in virus clearance or tumor rejection (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Human CD27 or CD70 deficiency due to genetic mutations resulted in persistent symptomatic EBV infection and EBV-associated lymphoproliferative disorders, including lethal lymphoma (26)(27)(28)(29)(30). In contrast, triggering CD27 persistently, such as by constitutively expressing CD70 in transgenic mouse models, resulted in a progressive and ultimately lethal deficiency in T cells, NK cells, and B cells due to direct exhaustion and activationinduced cell death (AICD) or IFN-g-mediated indirect depletion (31)(32)(33)(34).…”

mentioning

confidence: 99%

CD27-Mediated Regulatory T Cell Depletion and Effector T Cell Costimulation Both Contribute to Antitumor Efficacy

Wasiuk

Testa

Weidlick

et al. 2017

The Journal of Immunology

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CD27, a member of the TNFR superfamily, is constitutively expressed in most T cells and plays crucial roles in T cell effector functions. The costimulation and antitumor activity of CD27 agonistic Abs have been well documented in mouse models. Clinical testing of a human IgG1 anti-CD27 Ab, varlilumab (clone 1F5), is ongoing in cancer patients. In this study, we set out to further understand CD27 as an immunomodulatory target and to address the mechanism of antitumor efficacy using different IgG isotypes of 1F5 in human CD27-transgenic mice. 1F5mIgG1, the only isotype engaging inhibitory FcγRIIB expressed in B cells, elicited the most potent and broad immune response, but terminal differentiation, exhaustion, and apoptosis in the activated effector T cells were inevitable. Accordingly, this isotype was the most effective in eradicating BCL1 lymphoma but had limited efficacy in s.c. tumors. Conversely, 1F5mIgG2a, which interacts with cells expressing activating FcγRs, led to moderate immune activation, as well as to prominent reduction in the number and suppressive activity of regulatory T cells. These combined mechanisms imparted potent antitumor activity to 1F5mIgG2a, particularly against the s.c. tumors. 1F5hIgG1, varlilumab, showed balanced agonistic activity that was prominent at lower doses and depleting activity that was greater at higher doses. 1F5hIgG1 had good antitumor activity in all tumor models tested. Thus, both agonist and depleting properties contribute to the antitumor efficacy of CD27-targeted immunotherapy, and modulation of these activities in patients may be achieved by varying the dose and regimen.

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Combined immunodeficiency and Epstein-Barr virus–induced B cell malignancy in humans with inherited CD70 deficiency

Abstract: Abolhassani et al. show that CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of CD27 deficiency. CD70–CD27 interactions play a nonredundant role regulating humoral- and cell-mediated immunity in humans, especially for control of EBV.

Cited by 129 publications

References 56 publications

Infectious and Noninfectious Pulmonary Complications in Patients With Primary Immunodeficiency Disorders

Infectious and Noninfectious Pulmonary Complications in Patients With Primary Immunodeficiency Disorders

Th17 immune microenvironment in Epstein-Barr virus–negative Hodgkin lymphoma: implications for immunotherapy

CD27-Mediated Regulatory T Cell Depletion and Effector T Cell Costimulation Both Contribute to Antitumor Efficacy

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