Characterization of high-risk HIV-1 seronegative hemophiliacs.
Mechanisms that protect most high-risk HIV-1 seronegative (HRSN) persons are not well understood. Among hemophiliacs from the Multicenter Hemophilia Cohort Study who remained HIV-1 seronegative despite a high (94%) risk for acquisition of HIV-1 infection, only 7/43 were homozygous for the protective CCR5 Delta32 polymorphism. Among the remainder, neither CCR5 density nor beta-chemokine production, nor in vitro susceptibility to infection with the HIV-1 isolate JR-FL could distinguish HRSN hemophiliacs from healthy controls. When compared to lymphocytes of healthy controls not at risk for HIV-1 infection, diminished spontaneous lymphocyte proliferation was seen in lymphocytes of HRSN hemophiliacs as well as in lymphocytes of hemophiliacs not at risk for HIV-1 infection. Surprisingly sera/plasmas obtained from high-risk HIV-1 seropositve hemophiliacs prior to seroconversion more often contained alloreactive antibodies than date-matched sera/plasmas obtained from HRSN hemophiliacs. Thus alloreactivity may predispose to acquisition of HIV-1 infection after parenteral exposure.
Salkowitz
J R
JR
Division of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
Purvis
S F
SF
Meyerson
H
H
Zimmerman
P
P
O'Brien
T R
TR
Aledort
L
L
Eyster
M E
ME
Hilgartner
M
M
Kessler
C
C
Konkle
B A
BA
White
G C
GC
Goedert
J J
JJ
Lederman
M M
MM
D000293:Adolescent; D000328:Adult; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000097:blood; D002648:Child; D015331:Cohort Studies; D004340:Drug Contamination; D005169:Factor VIII / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000635:transmission; D018023:HIV Seronegativity; D006679:HIV Seropositivity; D015497:HIV-1; D006467:Hemophilia A / Q000453:epidemiology* / Q000235:genetics / Q000628:therapy; D006358:Hot Temperature; D006801:Humans; D007113:Immunity, Innate; D007518:Isoantibodies / Q000097:blood; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000097:blood; D008297:Male; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics; D012306:Risk
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D007518:Isoantibodies; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D005169:Factor VIII