TY - JOUR

T1 - The extent of B-cell activation and dysfunction preceding lymphoma development in HIV-positive people

AU - Shepherd, L.

AU - Borges, H.

AU - Harvey, R.

AU - Bower, M.

AU - Grulich, A.

AU - Silverberg, M.

AU - Weber, J.

AU - Ristola, M.

AU - Viard, J. P.

AU - Bogner, J. R.

AU - Gargalianos-Kakolyris, P.

AU - Mussini, C.

AU - Mansinho, K.

AU - Yust, I.

AU - Paduta, D.

AU - Jilich, D.

AU - Smiatacz, T.

AU - Radoi, R.

AU - Tomazic, J.

AU - Plomgaard, P.

AU - Frikke-Schmidt, R.

AU - Lundgren, J.

AU - Mocroft, A.

AU - Losso, M.

AU - Kundro, M.

AU - Kronborg, G.

AU - Benfield, T.

AU - Gerstoft, J.

AU - Katzenstein, T.

AU - Møller, N. F.

AU - Pedersen, C.

AU - Ostergaard, L.

AU - Wiese, L.

AU - Nielsen, L. N.

AU - Schmidt, R.

AU - Szlávik, J.

AU - Bruun, J.

AU - Victor, B.

AU - Johnson, A. M.

AU - Johnson, M. A.

AU - Pedersen, C.

AU - Kirk, O.

AU - Peters, L.

AU - Fischer, A. H.

AU - Bojesen, A.

AU - Raben, D.

AU - Kristensen, D.

AU - Larsen, J. F.

AU - Podlekareva, D.

AU - EuroSIDA in EuroCoord

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - B-cell dysfunction

KW - biomarkers

KW - free light chains

KW - HIV

KW - immunoglobulins

KW - lymphoma

U2 - 10.1111/hiv.12546

DO - 10.1111/hiv.12546

M3 - Journal article

C2 - 28857427

AN - SCOPUS:85028644376

VL - 19

SP - 90

EP - 101

JO - HIV Medicine

JF - HIV Medicine

SN - 1464-2662

IS - 2

ER -