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

EuroSIDA in EuroCoord

doi:10.1111/hiv.12546

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

EuroSIDA in EuroCoord

Institut for Klinisk Medicin

5 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	HIV Medicine
Vol/bind	19
Udgave nummer	2
Sider (fra-til)	90-101
Antal sider	12
ISSN	1464-2662
DOI	https://doi.org/10.1111/hiv.12546
Status	Udgivet - feb. 2018

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10.1111/hiv.12546

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title = "The extent of B-cell activation and dysfunction preceding lymphoma development in HIV-positive people",

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.",

keywords = "B-cell dysfunction, biomarkers, free light chains, HIV, immunoglobulins, lymphoma",

author = "L. Shepherd and H. Borges and R. Harvey and M. Bower and A. Grulich and M. Silverberg and J. Weber and M. Ristola and Viard, {J. P.} and Bogner, {J. R.} and P. Gargalianos-Kakolyris and C. Mussini and K. Mansinho and I. Yust and D. Paduta and D. Jilich and T. Smiatacz and R. Radoi and J. Tomazic and P. Plomgaard and R. Frikke-Schmidt and J. Lundgren and A. Mocroft and M. Losso and M. Kundro and G. Kronborg and T. Benfield and J. Gerstoft and T. Katzenstein and M{\o}ller, {N. F.} and C. Pedersen and L. Ostergaard and L. Wiese and Nielsen, {L. N.} and R. Schmidt and J. Szl{\'a}vik and J. Bruun and B. Victor and Johnson, {A. M.} and Johnson, {M. A.} and C. Pedersen and O. Kirk and L. Peters and Fischer, {A. H.} and A. Bojesen and D. Raben and D. Kristensen and Larsen, {J. F.} and D. Podlekareva and {EuroSIDA in EuroCoord}",

year = "2018",

month = feb,

doi = "10.1111/hiv.12546",

language = "English",

volume = "19",

pages = "90--101",

journal = "HIV Medicine",

issn = "1464-2662",

publisher = "Wiley-Blackwell",

number = "2",

}

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 - 2018/2

Y1 - 2018/2

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

SN - 1464-2662

VL - 19

SP - 90

EP - 101

JO - HIV Medicine

JF - HIV Medicine

IS - 2

ER -

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

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