scholarly journals Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency

2005 ◽  
Vol 202 (4) ◽  
pp. 479-484 ◽  
Author(s):  
William H. Wheat ◽  
Carlyne D. Cool ◽  
Yoshikazu Morimoto ◽  
Pradeep R. Rai ◽  
Charles H. Kirkpatrick ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
B Cell ◽  
Common Variable Immunodeficiency ◽  
B Cell Lymphoma ◽  
Lymphoproliferative Disorders ◽  
Nuclear Antigen ◽  
Qrt Pcr ◽  
Hhv8 Infection ◽  
Common Variable

Patients who have common variable immunodeficiency (CVID) and granulomatous/lymphocytic interstitial lung disease (GLILD) are at high risk for early mortality and B cell lymphomas. Infection with human herpes virus type 8 (HHV8), a B cell lymphotrophic virus, is linked to lymphoproliferative disorders in people who have secondary immunodeficiencies. Therefore, we determined the prevalence of HHV8 infection in CVID patients with GLILD. Genomic DNA isolated from peripheral blood mononuclear cells was screened by nested- and real time-quantitative PCR (QRT-PCR) for the presence of HHV8 genome. It was positive in 6/9 CVID patients with GLILD (CVID-GLILD), 1/21 CVID patients without GLILD (CVID-control), and no patients receiving intravenous gamma globulin (n = 13) or normal blood donors (n = 20). Immunohistochemistry (IHC) demonstrated expression of the latency-associated nuclear antigen-1 (LANA-1) in the biopsies of the lung, liver, and bone marrow of four patients with CVID-GLILD. One CVID-GLILD patient developed a B cell lymphoma during the course of the study. QRT-PCR demonstrated high copy number of HHV8 genome and IHC showed diffuse staining for LANA-1 in the malignant lymph node. HHV8 infection may be an important factor in the pathogenesis of the interstitial lung disease and lymphoproliferative disorders in patients with CVID.

scholarly journals B Cell Dysregulation in Common Variable Immunodeficiency Interstitial Lung Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Erik M. Matson ◽  
Miranda L. Abyazi ◽  
Kayla A. Bell ◽  
Kevin M. Hayes ◽  
Paul J. Maglione
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
B Cell ◽  
Common Variable Immunodeficiency ◽  
Cell Biology ◽  
Gastrointestinal Disease ◽  
Expression Patterns ◽  
Granulomatous Inflammation ◽  
Lung Pathology ◽  
Common Variable

Common variable immunodeficiency (CVID) is the most frequently diagnosed primary antibody deficiency. About half of CVID patients develop chronic non-infectious complications thought to be due to intrinsic immune dysregulation, including autoimmunity, gastrointestinal disease, and interstitial lung disease (ILD). Multiple studies have found ILD to be a significant cause of morbidity and mortality in CVID. Yet, the precise mechanisms underlying this complication in CVID are poorly understood. CVID ILD is marked by profound pulmonary infiltration of both T and B cells as well as granulomatous inflammation in many cases. B cell depletive therapy, whether done as a monotherapy or in combination with another immunosuppressive agent, has become a standard of therapy for CVID ILD. However, CVID is a heterogeneous disorder, as is its lung pathology, and the precise patients that would benefit from B cell depletive therapy, when it should administered, and how long it should be repeated all remain gaps in our knowledge. Moreover, some have ILD recurrence after B cell depletive therapy and the relative importance of B cell biology remains incompletely defined. Developmental and functional abnormalities of B cell compartments observed in CVID ILD and related conditions suggest that imbalance of B cell signaling networks may promote lung disease. Included within these potential mechanisms of disease is B cell activating factor (BAFF), a cytokine that is upregulated by the interferon gamma (IFN-γ):STAT1 signaling axis to potently influence B cell activation and survival. B cell responses to BAFF are shaped by the divergent effects and expression patterns of its three receptors: BAFF receptor (BAFF-R), transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA). Moreover, soluble forms of BAFF-R, TACI, and BCMA exist and may further influence the pathogenesis of ILD. Continued efforts to understand how dysregulated B cell biology promotes ILD development and progression will help close the gap in our understanding of how to best diagnose, define, and manage ILD in CVID.

scholarly journals Airway and interstitial lung disease are distinct entities in paediatric common variable immunodeficiency

2011 ◽  
Vol 165 (2) ◽  
pp. 235-242 ◽  
Author(s):  
A. A. J. M. van de Ven ◽  
P. A. de Jong ◽  
D. P. Hoytema van Konijnenburg ◽  
O. A. M. Kessels ◽  
M. Boes ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Common Variable Immunodeficiency ◽  
Common Variable

Interstitial Lung Disease in Patients with Diffuse Large B-Cell Lymphoma Receiving CHOP-Based Chemotherapy Is Associated with the Use of Rituximab.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3435-3435 ◽  
Author(s):  
Ronald S. Go ◽  
Kevin M. Riggle ◽  
Sue A. Beier-Hanratty ◽  
Jacob D. Gundrum ◽  
Jonean E. Schroeder ◽  
...  
Keyword(s):  
Risk Factors ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Imaging Studies ◽  
Cardiopulmonary Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Several cases of chemotherapy-induced interstitial lung disease (ILD) or pneumonitis have been reported in recent years in patients with lymphoma. The potential roles of rituximab (R) and granulocyte colony stimulating factor (GCSF), agents more commonly used in recent years, are suggested. Objective: We wanted to determine the prevalence of ILD and identify risk factors in patients with diffuse large B-cell lymphoma (DLCL) who received cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP)-based chemotherapy. Methods: Selection criteria included newly diagnosed DLCL patients treated at our institution from 2000–2006 who received CHOP with or without R and had at least 3 serial CT or PET/CT scans during chemotherapy. ILD was defined as new bilateral interstitial pulmonary infiltrates not likely representing fluid overload or fibrosis. One radiologist blinded to clinical data reviewed all imaging studies. Results: Out of a total of 174 new cases of DLCL, 73 met our study criteria. Reasons for exclusion included no chemotherapy (45), <3 imaging studies (46), and non-CHOP-based chemotherapy (10). Among the 73 study patients, 52 (71%) received R in addition to CHOP. Eleven (15.1%) patients developed ILD, all in the subgroup that received RCHOP (P = 0.027). Most occurred between cycles 2 and 4 of RCHOP (81.8%) and persisted until after completion of chemotherapy (63.6%). Nine (81.8%) patients with ILD were asymptomatic and never required treatment or delay of RCHOP. The remaining 2 patients became symptomatic (1 hospitalized), were empirically treated for atypical pneumonia with clinical recovery, and had delay of RCHOP. All patients received the intended number of courses of RCHOP. Univariate analysis of potential ILD risk factors among those who received RCHOP showed a trend with the subgroup that either had GCSF or cardiopulmonary disease (P = 0.09). Multivariate analysis using a two-variable model suggests that the use of GCSF or presence of cardiopulmonary disease (P = 0.065) and a high (3–5) international prognostic index score (P = 0.13) need further investigation as risk factors. Conclusions: In our cohort of DLCL patients receiving CHOP-based chemotherapy, ILD was common and significantly associated with the use of R. While most cases were asymptomatic, self-limited, and did not require delay of chemotherapy, more serious presentation could occur. The mechanism of ILD is unknown and requires further investigation.

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