Volume 7 Supplement 1
Kaposi sarcoma herpesvirus (KSHV)-associated lymphomas are associated with markedly elevated serum IL-10, elevated IL-6, IL-17 and circulating KSHV
© Uldrick et al; licensee BioMed Central Ltd. 2012
Published: 19 April 2012
KSHV, also called human herpesvirsus-8 (HHV8), is the etiologic agent of primary effusion lymphoma (PEL) (including extracavitary variant), and large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease (together, KSHV-associated non-Hodgkin lymphoma (KSHV-NHL). Additional KSHV-associated diseases include: Kaposi sarcoma (KS), a form of multicentric Castleman disease (KSHV-MCD), and a proposed KSHV-associated inflammatory cytokine syndrome (KICS). Like KSHV-MCD, inflammatory symptoms are common in KSHV-NHL. We compared an array of inflammatory and angiogenic cytokines, chemokines, growth factors, and select clinical laboratory values between HIV-infected patients with KSHV-NHL and other lymphomas (HIV-lymphoma).
Patients were enrolled in HAMB and/or NIAID protocols. Cases had KSHV-NHL; controls other HIV-lymphoma. Clonality of PEL diagnosed from effusions was confirmed by PCR for immunoglobin rearrangements. Serum was evaluated by ELISA for IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, TNF-α, IL-17, VEGF-A, (Meso-Scale Discovery, Gathersberg, MD), CXCL1, VEGF-C (R&D Systems, Minneapolis, MN). In patients with KSHV-NHL, peripheral blood mononuclear cell associated KSHV viral load was measured. Clinical data included demographics, CD4 count, albumin, platelets, hemoglobin, and c-reactive protein (CRP). Comparison of each parameter between patients with KSHV-NHL and other HIV-lymphoma employed an exact form of the Wilcoxon rank-sum test. P-values are 2-sided, with p ≤ 0.01 considered statistically significant, and 0.01< p <0.05 considered strong trends.
Subjects:13 KSHV-NHL cases: 12 men, 1 woman. Median age 44, (IQR 39-55). 4 white, 4 Hispanic, 3 African-American, 2 African. PEL (8), extracavitary variant PEL (3), large B-cell lymphoma arising in HHV8-associated MCD (2, both with large effusions), history pathology confirmed KSHV-MCD (4). 28 HIV-associated lymphoma controls: 23 men, 5 women. Median age 38 (IQR 35-46). 17 white, 4 Hispanic, 6 African-American, 1 African. Histologies: primary central nervous system lymphoma (13), diffuse large B-cell lymphoma (DLBCL) (10), Hodgkin disease (1), Burkitt lymphoma (2), plasmablastic lymphoma (1), EBV+ large B-cell lymphoma NOS (1). KSHV-NHL subjects had elevated KSHV viral load, [median 2812 copies/106 cells (IQR 186-115,789)] and CRP [median 51 mg/L (IQR 45-67)]. Compared to other HIV-lymphomas, patients with KSHV-NHL have higher CD4 counts (median CD4 133 vs. 29 cells/uL, p=0.002), hypoalbuminema (median albumin 1.9 vs. 3.5 mg/dL, p= 0.0034)), and trend towards more severe anemia, thrombocytopenia, and hyponatremia. KSHV-NHL is associated with elevated circulating KSHV, marked elevations in IL-10 (513 vs. 12.2 pg/mL, p <0.0001), elevations in IL-6 (29 vs. 4.1 pg/mL, p=0.0013), IL-17 (1.6 vs. 0.5 pg/mL, p=0.0074), and trends towards increased IFN-γ and IL-1β.
Inflammatory cytokines are important n KSHV-NHL pathogenesis and symptomatology. Clinical and translational studies evaluating these abnormalities in KSHV-associated malignancies are ongoing.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.