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B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B-cell lymphoma.

ABSTRACT: BACKGROUND:The risk of developing non-Hodgkin lymphoma (NHL) is greatly increased in HIV infection. The aim of this study was to determine whether elevated serum levels of molecules associated with B-cell activation precede the diagnosis of AIDS-associated NHL (AIDS-NHL). METHODS:Serum levels of B-cell activation-associated molecules, interleukin (IL)6, IL10, soluble CD23 (sCD23), sCD27, sCD30, C-reactive protein (CRP), and immunoglobulin E were determined in 179 NHL cases and HIV+ controls in the Multicenter AIDS Cohort Study, collected at up to 3 time points per subject, 0 to 5 years prior to AIDS-NHL diagnosis. RESULTS:Serum IL6, IL10, CRP, sCD23, sCD27, and sCD30 levels were all significantly elevated in the AIDS-NHL group, when compared with HIV+ controls or with AIDS controls, after adjusting for CD4 T-cell number. Elevated serum levels of B-cell activation-associated molecules were seen to be associated with the development of systemic [non-CNS (central nervous system)] NHL, but not with the development of primary CNS lymphoma. CONCLUSIONS:Levels of certain B-cell stimulatory cytokines and molecules associated with immune activation are elevated for several years preceding the diagnosis of systemic AIDS-NHL. This observation is consistent with the hypothesis that chronic B-cell activation contributes to the development of these hematologic malignancies. IMPACT:Marked differences in serum levels of several molecules are seen for several years prediagnosis in those who eventually develop AIDS-NHL. Some of these molecules may serve as candidate biomarkers and provide valuable information to better define the etiology of NHL.

SUBMITTER: Breen EC

PROVIDER: S-EPMC3132317 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B-cell lymphoma.

Breen Elizabeth Crabb EC Hussain Shehnaz K SK Magpantay Larry L Jacobson Lisa P LP Detels Roger R Rabkin Charles S CS Kaslow Richard A RA Variakojis Daina D Bream Jay H JH Rinaldo Charles R CR Ambinder Richard F RF Martinez-Maza Otoniel O

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20110428 7

<h4>Background</h4>The risk of developing non-Hodgkin lymphoma (NHL) is greatly increased in HIV infection. The aim of this study was to determine whether elevated serum levels of molecules associated with B-cell activation precede the diagnosis of AIDS-associated NHL (AIDS-NHL).<h4>Methods</h4>Serum levels of B-cell activation-associated molecules, interleukin (IL)6, IL10, soluble CD23 (sCD23), sCD27, sCD30, C-reactive protein (CRP), and immunoglobulin E were determined in 179 NHL cases and HIV ...[more]

PMID: 21527584

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Project description:BackgroundThe prevalence, pathology, and existence of malnutrition-associated diabetes remain uncertain, especially with respect to adult-acquired undernutrition.ObjectiveThe aim was to investigate the association of prior undernutrition (low BMI, in kg/m2), acquired in adulthood and insulin during an oral glucose tolerance test (OGTT).MethodsWe followed up 630 adults recruited 7-14 y previously for other studies. Plasma insulin was measured fasting and at 30 and 120 min during an OGTT. The main exposure was BMI measured 7-14 y prior. The main outcome of interest was plasma insulin, controlling for time during the OGTT using generalized estimating equations, and exploratory outcomes were early insulin response (relative change in insulin and glucose from 0-30 min) and relative insulin and glucose AUCs from 0 to 120 min. Current confounding factors were age, sex, BMI, HIV, socioeconomic status, and physical activity.ResultsIn unadjusted analyses, increasing severity of prior malnutrition was associated with lower insulin concentration. In multivariate adjusted analyses, only current BMI was a strong predictor of overall insulin concentration. Associations with prior BMI of insulin responses accounting for glucose were also seen in unadjusted but not adjusted analyses. For insulin concentration but not the outcomes accounting for glucose, there was a sex interaction with prior BMI such that only men had lower insulin if previously malnourished: insulin (pmol/L) at 120 min was 311 (95% CI: 272, 351) for prior BMI ≥18.5, 271 (95% CI: 221, 321) for prior BMI 17.0-18.5, and 237 (95% CI: 194, 297) for prior BMI <17.0; P = 0.03. HIV status showed limited and variable associations with insulin.ConclusionsInsulin concentration, fasting and during an OGTT, was normalized in women more than in men several years after adult malnutrition. Chronic malnutrition, as indicated by low prior and current BMI, may contribute to diabetes through low insulin secretion.

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B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B-cell lymphoma.

Publications

B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B-cell lymphoma.

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