Circulating serum free light chains as predictive markers of AIDS-related lymphoma.
PURPOSE HIV-infected persons have an elevated risk of developing non-Hodgkin's lymphoma (NHL); this risk remains increased in the era of effective HIV therapy. We evaluated serum immunoglobulin (Ig) proteins as predictors of NHL risk among HIV-infected individuals. PATIENTS AND METHODS By using three cohorts of HIV-infected persons (from 1982 to 2005), we identified 66 individuals who developed NHL and 225 matched (by cohort, sex, ethnicity, age, and CD4 count), HIV-infected, lymphoma-free controls who had available stored prediagnostic blood samples. Serum/plasma samples obtained 0 to 2 years and 2 to 5 years before diagnosis/selection were assayed for IgG, IgM, and IgA levels; monoclonal (M) Igs; and kappa and lambda free light chain (FLC) levels. Patients and matched controls were compared by using conditional logistic regression. Results The kappa and lambda FLCs were both significantly higher in patients (eg, in 2- to 5-year window: median kappa, 4.24 v 3.43 mg/dL; median lambda, 4.04 v 3.09 mg/dL) and strongly predicted NHL in a dose-response manner up to 2 to 5 years before diagnosis/selection (eg, NHL risk 3.76-fold higher with kappa concentration at least 2.00 times the upper limit of normal, and 8.13-fold higher with lambda concentration at least 2.00 times the upper limit of normal compared with normal levels). In contrast, IgG, IgM, and IgA levels were similar in patients and controls. M proteins were detected in only two patients with NHL (3%) and in nine controls (4%), and they were not significantly associated with NHL risk. CONCLUSION Elevated FLCs may represent sensitive markers of polyclonal B-cell activation and dysfunction and could be useful for identifying HIV-infected persons at increased NHL risk.
Landgren
Ola
O
National Cancer Institute, National Institutes of Health, Center for Cancer Research, Medical Oncology Branch, 9000 Rockville Pike, Bldg 10/Room 13N240, Bethesda, MD, 20892, USA. landgreo@mail.nih.gov
Goedert
James J
JJ
Rabkin
Charles S
CS
Wilson
Wyndham H
WH
Dunleavy
Kieron
K
Kyle
Robert A
RA
Katzmann
Jerry A
JA
Rajkumar
S Vincent
SV
Engels
Eric A
EA
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000097:blood*; D007146:Immunoglobulin lambda-Chains / Q000097:blood*; D016015:Logistic Models; D008213:Lymphocyte Activation; D016483:Lymphoma, AIDS-Related / Q000276:immunology* / Q000821:virology; D008297:Male; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000276:immunology / Q000821:virology; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains