title: Serum biomarkers of immune activation and subsequent risk of non-hodgkin B-cell lymphoma among HIV-infected women.
abstract: BACKGROUND
  There is increasing evidence that chronic immune activation predisposes to non-Hodgkin lymphoma (NHL). Whether this association exists among women representative of the current HIV epidemic in the United States who are at high risk of HIV-associated NHL (AIDS-NHL), remains to be determined.
  
  
  METHODS
  We conducted a nested case-control study within the Women's Interagency HIV Study with longitudinally collected risk factor data and sera. Cases were HIV-infected women with stored sera collected at three time-windows 3 to 5 years, 1 to 3 years, and 0 to 1 year before AIDS-NHL diagnosis (n = 22). Three to six HIV-infected controls, without AIDS-NHL, were matched to each case on age, race, CD4(+) T-cell count, and study follow-up time (n = 78). ORs and 95% confidence intervals (CI) for the association between one unit increase in log-transformed biomarker levels and AIDS-NHL were computed using random effect multivariate logistic regression models.
  
  
  RESULTS
  Elevated levels of sCD27 (OR = 7.21; 95% CI, 2.62-19.88), sCD30 (OR = 2.64; 95% CI, 1.24-5.64), and CXCL13 (OR = 2.56; 95% CI, 1.32-4.96) were associated with subsequent diagnosis of AIDS-NHL overall. Elevated sCD23 was associated with a two to three-fold increased risk of AIDS-NHL in certain subgroups, whereas elevated interleukin 6 was associated with a two-fold increased risk in the 0 to 1 year time-window, only.
  
  
  CONCLUSIONS
  These findings support the hypothesis that chronic B-cell activation contributes to the development of AIDS-NHL in women.
  
  
  CONCLUSIONS
  Soluble CD23 (sCD23), sCD27, sCD30, and CXCL13 may serve as biomarkers for AIDS-NHL.
authors.affiliation: Authors' Affiliations: Department of Epidemiology, Fielding School of Public Health; Jonsson Comprehensive Cancer Center; Departments of Psychiatry and Biobehavioral Sciences, and Obstetrics & Gynecology, and Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at UCLA; UCLA AIDS Institute; University of California; Keck School of Medicine, University of Southern California, Los Angeles; Departments of Clinical Pharmacy and of Medicine, University of California, San Francisco; Department of Hematology/HCT, City of Hope National Medical Center, Duarte, California; Departments of Medicine and Epidemiology & Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx; SUNY Downstate Medical Center, Brooklyn, New York; CORE Center of Cook County Health and Hospitals System and Departments of Medicine, Rush University and Cook County Health and Hospitals System, Chicago, Illinois; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Departments of Pathology, Medicine, and Prevention and Community Health, George Washington University, Washington, DC.
authors.forename: Shehnaz K
authors.initials: SK
authors.lastname: Hussain
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Hessol
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Levine
authors.forename: Elizabeth Crabb
authors.initials: EC
authors.lastname: Breen
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Mardge
authors.initials: M
authors.lastname: Cohen
authors.forename: Gypsyamber
authors.initials: G
authors.lastname: D'Souza
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Gustafson
authors.forename: Sylvia
authors.initials: S
authors.lastname: Silver
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D016483:Lymphoma, AIDS-Related / Q000097:blood / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000097:blood / Q000276:immunology* / Q000821:virology*; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor
references.citation: Cancer Epidemiol Biomarkers Prev. 2011 Aug;20(8):1571-9
references.pmid: 21750174
references.citation: AIDS. 2001 Mar 30;15(5):629-33
references.pmid: 11317001
references.citation: Cancer Res. 2012 Sep 15;72(18):4733-43
references.pmid: 22846913
references.citation: Clin Diagn Lab Immunol. 2005 Sep;12(9):1013-9
references.pmid: 16148165
references.citation: Biometrics. 1992 Jun;48(2):631-44
references.pmid: 1637985
references.citation: J Rheumatol. 2000 Mar;27(3):698-702
references.pmid: 10743811
references.citation: J Proteome Res. 2011 Jan 7;10(1):113-9
references.pmid: 20886858
references.citation: AIDS. 2007 Nov 12;21(17):2265-70
references.pmid: 18090274
references.citation: Am J Public Health. 2004 Jul;94(7):1147-51
references.pmid: 15226135
references.citation: J Exp Med. 1998 Feb 16;187(4):655-60
references.pmid: 9463416
references.citation: J Exp Med. 2003 May 5;197(9):1173-81
references.pmid: 12732658
references.citation: AIDS. 1994 Jun;8(6):741-5
references.pmid: 8086130
references.citation: Nature. 2002 Mar 7;416(6876):94-9
references.pmid: 11882900
references.citation: J Clin Oncol. 2010 Feb 10;28(5):773-9
references.pmid: 20048176
references.citation: AIDS. 2013 Jan 28;27(3):469-74
references.pmid: 23169327
references.citation: Blood. 2009 Sep 24;114(13):2730-2
references.pmid: 19638620
references.citation: Clin Immunol. 1999 Sep;92(3):293-9
references.pmid: 10479534
references.citation: Allergy. 2001 Jul;56(7):593-603
references.pmid: 11421916
references.citation: Immunol Rev. 2009 May;229(1):216-31
references.pmid: 19426224
references.citation: Epidemiology. 1998 Mar;9(2):117-25
references.pmid: 9504278
references.citation: Leukemia. 2010 May;24(5):1018-24
references.pmid: 20357822
references.citation: Nature. 2000 Jul 20;406(6793):309-14
references.pmid: 10917533
references.citation: Curr Opin Oncol. 2006 Sep;18(5):444-8
references.pmid: 16894291
references.citation: Clin Immunol. 1999 Dec;93(3):239-44
references.pmid: 10600334
references.citation: Blood. 1995 Apr 1;85(7):1843-9
references.pmid: 7703491
references.citation: J Interferon Cytokine Res. 2005 Nov;25(11):702-6
references.pmid: 16318584
references.citation: AIDS. 2011 Jan 28;25(3):303-14
references.pmid: 21192231
references.citation: Blood. 2007 Jul 15;110(2):695-708
references.pmid: 17389762
references.citation: Am J Hematol. 2011 Oct;86(10):875-8
references.pmid: 22022727
references.citation: Clin Immunol. 1999 Nov;93(2):114-23
references.pmid: 10527687
references.citation: Clin Exp Rheumatol. 1995 May-Jun;13(3):339-43
references.pmid: 7554561
references.citation: Histol Histopathol. 2000 Apr;15(2):573-6
references.pmid: 10809378
references.citation: Cancer Epidemiol Biomarkers Prev. 2013 Feb;22(2):295-307
references.pmid: 23250934
references.citation: Cancer Epidemiol Biomarkers Prev. 2011 Jul;20(7):1303-14
references.pmid: 21527584