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HIV Med. 2018 Feb;19(2):90-101. doi: 10.1111/hiv.12546. Epub 2017 Aug 31.

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

Collaborators (178)

Losso M, Kundro M, Schmied B, Karpov I, Vassilenko A, Mitsura VM, Paduto D, Clumeck N, De Wit S, Delforge M, Florence E, Vandekerckhove L, Hadziosmanovic V, Begovac J, Machala L, Sedlacek D, Kronborg G, Benfield T, Gerstoft J, Katzenstein T, Møller NF, Pedersen C, Ostergaard L, Wiese L, Nielsen LN, Zilmer K, Jelena Smidt, Nakkusosakond Siseklinik, Kohtla-Järve, Ristola M, Aho I, Girard PM, Pradier C, Fontas E, Duvivier C, Rockstroh J, Schmidt R, Degen O, Stellbrink HJ, Stefan C, Fätkenheuer G, Chkhartishvili N, Gargalianos P, Xylomenos G, Armenis K, Sambatakou H, Szlávik J, Gottfredsson M, Mulcahy F, Turner D, Burke M, Shahar E, Hassoun G, Elinav H, Haouzi M, Elbirt D, Sthoeger ZM, D'Arminio Monforte A, Esposito R, Mazeu I, Mazzotta F, Gabbuti A, Vullo V, Lichtner M, Zaccarelli M, Antinori A, Acinapura R, Plazzi M, Lazzarin A, Castagna A, Gianotti N, Galli M, Ridolfo A, Sacco OL, Rozentale B, Uzdaviniene V, Matulionyte R, Staub T, Hemmer R, Reiss P, Ormaasen V, Maeland A, Bruun J, Knysz B, Gasiorowski J, Inglot M, Horban A, Bakowska E, Flisiak R, Grzeszczuk A, Parczewski M, Maciejewska K, Aksak-Was B, Beniowski M, Mularska E, Gensing M, Jablonowska E, Malolepsza E, Wojcik K, Mozer-Lisewska I, Caldeira L, Maltez F, Oprea C, Victor Babes, Panteleev A, Panteleev O, Yakovlev A, Trofimora T, Khromova I, Kuzovatova E, Borodulina E, Vdoushkina E, Jevtovic D, Gatell JM, Miró JM, Moreno S, Rodriguez JM, Clotet B, Jou A, Paredes R, Tural C, Puig J, Bravo I, Domingo P, Gutierrez M, Mateo G, Sambeat MA, Laporte JM, Falconer K, Thalme A, Sonnerborg A, Blaxhult A, Flamholc L, Scherrer A, Weber R, Cavassini M, Calmy A, Furrer H, Battegay M, Schmid P, Kuznetsova A, Kyselyova G, Sluzhynska M, Gazzard B, Johnson AM, Simons E, Edwards S, Phillips A, Johnson MA, Mocroft A, Orkin C, Scullard G, Clarke A, Leen C, Gatell J, Gazzard B, Horban A, Karpov I, Losso M, d'Arminio Monforte A, Pedersen C, Reiss P, Rockstroh J, Rockstroh J, Kirk O, Kirk O, Peters L, Matthews C, Fischer AH, Bojesen A, Raben D, Kristensen D, Grønborg Laut K, Larsen JF, Podlekareva D, Cozzi-Lepri A, Schultze A, Amele S.

Author information

1
Research Department of Infection and Population Health, University College London, London, UK.
2
Centre of Excellence for Health, Immunity and Infections, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
3
Charing Cross Oncology Laboratory and Trophoblastic Disease Centre, Charing Cross Hospital Campus of Imperial College Healthcare National Health Service Trust, London, UK.
4
National Centre for HIV Malignancy, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
5
Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.
6
Kaiser Permanente Northern California, Oakland, CA, USA.
7
Imperial College London, London, UK.
8
Division of Infectious Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
9
AP-HP, Diagnostic & Therapeutic Center, Hotel Dieu Hospital, Paris, France.
10
Department of Internal Medicine IV, University of Munich, Munich, Germany.
11
First Department of Internal Medicine and Infectious Diseases Unit, General Hospital of Athens "G. Gennimatas", Athens, Greece.
12
Clinic of Infectious and Tropical Diseases, University of Modena and Reggio Emilia, Azienda Policlinico, Modena, Italy.
13
Department of Infectious Diseases, Hospital Egas Moniz-CHLO, E.P.E., Lisboa, Portugal.
14
Ichilov Hospital, Tel Aviv, Israel.
15
Gomel Regional Centre for Hygiene, Gomel, Belarus.
16
Department of Infectious and Tropical Diseases, First Faculty of Medicine, Charles University, Prague, Czech Republic.
17
Infectious Diseases Department, Medical University of Gdańsk, Gdańsk, Poland.
18
Clinical Hospital of Infectious and Tropical Diseases 'Dr. Victor Babeş', Bucharest, Romania.
19
Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia.
20
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.

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:

HIV ; B-cell dysfunction; biomarkers; free light chains; immunoglobulins; lymphoma

PMID:
28857427
DOI:
10.1111/hiv.12546
[Indexed for MEDLINE]

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