Shepherd, L;
Borges, AH;
Harvey, R;
Bower, M;
Grulich, A;
Silverberg, M;
Weber, J;
... Mocroft, A; + view all
(2018)
The extent of B-cell activation and dysfunction preceding lymphoma development in HIV-positive people.
HIV Medicine
, 19
(2)
pp. 90-101.
10.1111/hiv.12546.
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Abstract
OBJECTIVES: B-cell dysfunction and activation are thought to contribute to lymphoma development in HIV-positive people; however, the mechanisms are not well understood. We investigated levels of several markers of B-cell dysfunction [free light chain (FLC)-κ, FLC-λ, immunoglobulin G (IgG), IgA, IgM and IgD] prior to lymphoma diagnosis in HIV-positive people. METHODS: A nested matched case–control study was carried out within the EuroSIDA cohort, including 73 HIV-positive people with lymphoma and 143 HIV-positive lymphoma-free controls. Markers of B-cell dysfunction were measured in prospectively stored serial plasma samples collected before the diagnosis of lymphoma (or selection date in controls). Marker levels ≤ 2 and > 2 years prior to diagnosis were investigated. RESULTS: Two-fold higher levels of FLC-κ [odds ratio (OR) 1.84; 95% confidence interval (CI) 1.19, 2.84], FLC-λ (OR 2.15; 95% CI 1.34, 3.46), IgG (OR 3.05; 95% CI 1.41, 6.59) and IgM (OR 1.46; 95% CI 1.01, 2.11) were associated with increased risk of lymphoma > 2 years prior to diagnosis, but not ≤ 2 years prior. Despite significant associations > 2 years prior to diagnosis, the predictive accuracy of each marker was poor, with FLC-λ emerging as the strongest candidate with a c-statistic of 0.67 (95% CI 0.58, 0.76). CONCLUSIONS: FLC-κ, FLC-λ and IgG levels were higher > 2 years before lymphoma diagnosis, suggesting that B-cell dysfunction occurs many years prior to lymphoma development. However, the predictive value of each marker was low and they are unlikely candidates for risk assessment for targeted intervention.
| Type: | Article |
|---|---|
| Title: | The extent of B-cell activation and dysfunction preceding lymphoma development in HIV-positive people |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/hiv.12546 |
| Publisher version: | http://dx.doi.org/10.1111/hiv.12546 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Infectious Diseases, B-cell dysfunction, biomarkers, free light chains, HIV, immunoglobulins, lymphoma, Free Light-Chains, Active Antiretroviral Therapy, Non-Hodgkin-Lymphoma, Aids-Related Lymphoma, Cancer-Risk, United-States, Infection, Disease, Immunodeficiency, Inflammation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10042605 |
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