Cytokine changes during rituximab therapy in HIV-associated multicentric Castleman disease

Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. 4521-4524 ◽  
Author(s):  
Mark Bower ◽  
Ophelia Veraitch ◽  
Richard Szydlo ◽  
Peter Charles ◽  
Peter Kelleher ◽  
...  
Keyword(s):  
Immune Cell ◽  
Castleman Disease ◽  
Viral Loads ◽  
Multicentric Castleman Disease ◽  
Immunodeficiency Virus ◽  
Cytokine Levels ◽  
Plasma Cytokines ◽  
Inflammatory Cytokine Response ◽  
Systemic Symptoms ◽  
Anti Cd20

Abstract Recent data highlight the importance of inflammatory markers during human immunodeficiency virus type 1 (HIV) infection. HIV-associated multicentric Castleman disease (HIV-MCD) presents with systemic symptoms attributed to cytokine disarray, and we have previously shown that the use of the anti-CD20 monoclonal antibody rituximab induces clinical remissions. Before and during successful rituximab therapy, 15 plasma cytokines were measured as were adaptive (CD4, CD8, CD19) and innate (CD16/56) immune cell populations and HIV-1 viral loads. A significant reduction from baseline of the CD19 B-cell count, consistent with rituximab's mechanism of action, was observed. Markedly elevated cytokine levels were observed before rituximab therapy, and a reduction from baseline values with rituximab therapy was observed for interleukin (IL)-5, IL-6, and IL-10. Therapies that reduce the inflammatory cytokine response are likely to be successful in a range of diseases, including HIV-MCD, and in the future may be used to guide therapeutic strategies.

Plasma HHV8 DNA predicts relapse in individuals with HIV-associated multicentric Castleman disease

Blood ◽  
2011 ◽  
Vol 118 (2) ◽  
pp. 271-275 ◽  
Author(s):  
Justin Stebbing ◽  
Caroline Adams ◽  
Adam Sanitt ◽  
Salvinia Mletzko ◽  
Mark Nelson ◽  
...  
Keyword(s):  
Human Herpesvirus ◽  
Castleman Disease ◽  
Human Herpesvirus 8 ◽  
Histologic Diagnosis ◽  
Herpesvirus 8 ◽  
Multicentric Castleman Disease ◽  
Younger Age ◽  
Systemic Symptoms ◽  
Anti Cd20 ◽  
Active Attack

Abstract HIV-associated multicentric Castleman disease (HIV-MCD) is a rare lymphoproliferative disorder caused by infection with human herpesvirus-8. The disease follows a relapsing and remitting clinical course, with marked systemic symptoms during an active attack, which can prove fatal. Its incidence is rising, and new data indicate the utility of the anti-CD20 monoclonal antibody rituximab at inducing remissions in both first- and second-line settings, although biomarkers associated with relapse have not been previously identified. In 52 individuals with a histologic diagnosis of HIV-MCD, we performed univariate and multivariate analyses to predict factors associated with an HIV-MCD attack. Although a younger age (< 50 years) was associated with an attack, the strongest association was observed with plasma levels of human herpesvirus-8 DNA. Rising levels predicted an attack (hazard ratio = 2.9; 95% confidence interval, 1.3-6.7), and maintenance therapy with rituximab should be considered in these individuals.

scholarly journals The Contribution of Kaposi’s Sarcoma–Associated Herpesvirus to Mortality in Hospitalized Human Immunodeficiency Virus–Infected Patients Being Investigated for Tuberculosis in South Africa

2019 ◽  
Vol 220 (5) ◽  
pp. 841-851 ◽  
Author(s):  
Melissa J Blumenthal ◽  
Charlotte Schutz ◽  
David Barr ◽  
Michael Locketz ◽  
Vickie Marshall ◽  
...  
Keyword(s):  
South Africa ◽  
Human Immunodeficiency Virus ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Castleman Disease ◽  
South Africans ◽  
Multicentric Castleman Disease ◽  
Immunodeficiency Virus ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

AbstractBackgroundDespite increasing numbers of human immunodeficiency virus (HIV)–infected South Africans receiving antiretroviral therapy (ART), tuberculosis (TB) remains the leading cause of mortality. Approximately 25% of patients treated for TB have microbiologically unconfirmed diagnoses. We assessed whether elevated Kaposi’s sarcoma–associated herpesvirus (KSHV) viral load (VL) contributes to mortality in hospitalized HIV-infected patients investigated for TB.MethodsSix hundred eighty-two HIV-infected patients admitted to Khayelitsha Hospital, South Africa, were recruited, investigated for TB, and followed for 12 weeks. KSHV serostatus, peripheral blood KSHV-VL, and KSHV-associated clinical correlates were evaluated.ResultsMedian CD4 count was 62 (range, 0–526) cells/μL; KSHV seropositivity was 30.7% (95% confidence interval [CI], 27%–34%); 5.8% had detectable KSHV-VL (median, 199.1 [range, 13.4–2.2 × 106] copies/106 cells); 22% died. Elevated KSHV-VL was associated with mortality (adjusted odds ratio, 6.5 [95% CI, 1.3–32.4]) in patients without TB or other microbiologically confirmed coinfections (n = 159). Six patients had “possible KSHV-inflammatory cytokine syndrome” (KICS): 5 died, representing significantly worse survival (P &lt; .0001), and 1 patient was diagnosed with KSHV-associated multicentric Castleman disease at autopsy.ConclusionsGiven the association of mortality with elevated KSHV-VL in critically ill HIV-infected patients with suspected but not microbiologically confirmed TB, KSHV-VL and KICS criteria may guide diagnostic and therapeutic evaluation.

scholarly journals Chronic Myelomonocytic Leukemia following Multicentric Castleman Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Feng Li ◽  
Xiaomei Zhang ◽  
Yanting Guo ◽  
Yuandong Zhu ◽  
Yicun Wu ◽  
...  
Keyword(s):  
Lymphoproliferative Disorder ◽  
Pluripotent Stem Cell ◽  
Underlying Mechanism ◽  
Castleman Disease ◽  
Chronic Myelomonocytic Leukemia ◽  
Cell Precursor ◽  
Multicentric Castleman Disease ◽  
Night Sweats ◽  
Systemic Symptoms ◽  
Myelomonocytic Leukemia

Multicentric Castleman disease (MCD) is a rare nonmalignant lymphoproliferative disorder presenting systemic symptoms such as fever, night sweats, fatigue, anemia, effusions, and multifocal lymphadenopathy. The etiology of MCD has not been clarified to date. The coexistence of MCD with chronic myelomonocytic leukemia (CMML) has been rarely reported. Although the pathogenesis remains unclear, this association probably reflects an incidental and fortuitous finding rather than the alteration of a common pluripotent stem cell precursor. Herein, we report on one case of MCD coexisting with CMML and elucidate the underlying mechanism of pathology in some aspects.

scholarly journals Reliability of self-sampling for accurate assessment of respiratory virus viral and immunologic kinetics

2020 ◽  
Author(s):  
Alpana Waghmare ◽  
Elizabeth M. Krantz ◽  
Subhasish Baral ◽  
Emma Vasquez ◽  
Tillie Loeffelholz ◽  
...  
Keyword(s):  
Immune Responses ◽  
Respiratory Virus ◽  
Viral Infections ◽  
Immune Cell ◽  
Cell Of Origin ◽  
Virus Shedding ◽  
Viral Loads ◽  
Home Based ◽  
Cytokine Levels ◽  
Respiratory Viral Infections

AbstractThe SARS-CoV-2 pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with foam swabs is well-tolerated and provides quantitative viral output concordant with flocked swabs. Using longitudinal home-based self-sampling, we demonstrate nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction using mathematical models. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.

scholarly journals HIV-associated multicentric Castleman disease: a report of 19 cases at an oncology institution

2020 ◽  
Vol 31 (4) ◽  
pp. 318-325 ◽  
Author(s):  
P Volkow-Fernández ◽  
C Lome-Maldonado ◽  
H Quintero-Buenrostro ◽  
B Islas-Muñoz ◽  
P Cornejo-Juárez
Keyword(s):  
Clinical Characteristics ◽  
Plasma Cells ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
People Living With Hiv ◽  
Multicentric Castleman Disease ◽  
Positron Emission ◽  
Systemic Symptoms ◽  
Clinical Records ◽  
Living With Hiv

The aim of this study is to describe the clinical characteristics and outcome of multicentric Castleman disease (MCD) in HIV-infected patients at an oncological referral center in Mexico. Clinical records at the HIV-AIDS clinic of all patients diagnosed with MCD from 1994 to 2018 were reviewed. There were 19 patients, mean age was 31.3 ± 8.4 years, and 17 (89.5%) were males. Fifteen patients (79%) had also Kaposi sarcoma (KS). Main clinical characteristics were multiple lymphadenopathy (95%), systemic symptoms (63%), and hepatosplenomegaly (50%). Computed tomography scan and 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography showed multiple lymphadenopathy, inversion of the liver:spleen uptake ratio, with an increase in SUVmax (5.7). The histopathology report described plasma cells in 58%, mixed type in 26%, and hyaline vascular in 16%. Eleven patients (57.9%) received different chemotherapy regimens. Seven patients died (36.8%): four related to MCD progression or chemotherapy complications, median survival was eight months. For those patients who survived, median, follow-up was 28 months (p < 0.001). The incidence of MCD in people living with HIV is probably underestimated. In patients with lymphadenopathy, B symptoms, deranged inflammatory markers, and/or disseminated KS, a biopsy of an enlarged lymph node is warranted, and the histology should be reviewed by an experienced pathologist.

Long-term remission of Kaposi sarcoma–associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3473-3475 ◽  
Author(s):  
Mario Corbellino ◽  
Giovanna Bestetti ◽  
Chiara Scalamogna ◽  
Sara Calattini ◽  
Morena Galazzi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Dna Sequences ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Quantitative Polymerase Chain Reaction ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Peripheral Blood Mononuclear ◽  
Multicentric Castleman Disease ◽  
Anti Cd20

Abstract Kaposi sarcoma–associated herpesvirus (KSHV)–related multicentric Castleman disease (MCD) is potentially lethal. Growing evidence indicates that, as in Epstein-Barr virus–driven lymphoproliferative disorders after transplantation, KSHV DNA burden in peripheral blood mononuclear cells (PBMCs) may represent the most accurate marker of disease activity. This report describes a patient with human immunodeficiency virus who was followed up clinically and by quantitative polymerase chain reaction for KSHV DNA sequences in PBMCs for more than 3 years following the diagnosis of KSHV-related MCD. Therapy with the antiherpesvirus agent cidofovir, antihuman interleukin-6 antibody BE-8, antiblastic chemotherapy, and combination antiretroviral agents did not achieve durable clinical or virologic remission of the disease. By contrast, administration of the anti-CD20 monoclonal antibody rituximab was well tolerated and allowed a 14-month remission of clinical symptoms and KSHV viremia. Rituximab should be added to the therapeutic armamentarium for KSHV-related MCD.

scholarly journals Failure of rituximab in human immunodeficiency virus-associated multicentric Castleman disease

2005 ◽  
Vol 79 (4) ◽  
pp. 337-339 ◽  
Author(s):  
Ségolène Neuville ◽  
Felix Agbalika ◽  
Claire Rabian ◽  
Josette Brière ◽  
Jean-Michel Molina
Keyword(s):  
Human Immunodeficiency Virus ◽  
Castleman Disease ◽  
Multicentric Castleman Disease ◽  
Immunodeficiency Virus
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