SERUM FREE LIGHT CHAINS IN PATIENTS WITH HIV NOT ON
ANTIRETROVIRAL THERAPY
A.E. Zemlin1, H Ipp2, S Maleka1, M.A. Rensburg1, R.T. Erasmus1
1Division
of Chemical Pathology, Department of Pathology, University of Stellenbosch and NHLS, Tygerberg Hospital, Cape Town, South Africa.
2Division of Haematology, Department of Pathology, University of Stellenbosch and NHLS, Tygerberg Hospital, Cape Town, South Africa.
Background
Results
Monoclonal serum free light chain (FLC) measurements
are used to follow up and manage patients with
monoclonal gammopathies and abnormal serum free
light chain (FLC) ratios have been associated with risk of
progression in certain diseases.
Kappa () and lambda () FLC are produced in excess
during the synthesis of immunoglobulins and are
excreted by the kidneys. Using these results a / ratio
can be calculated. Excess FLC levels may be due to
excess immunoglobulin synthesis as occurs in B-cell
dysfunction and an abnormal / ratio points to
monoclonal immunoglobulin synthesis.
Our study population consisted of 72 (63%) newly diagnosed HIV positive subjects and 42 (37%) HIV negative
subjects, all of Black ethnicity. The entire cohort consisted of 83 (80%) females and 21(20%) males. The ages
ranged from 21 to 60 years with a mean age of 33 years. They were recruited from a voluntary testing walk-in
clinic in Crossroads, Cape Town.
B-cell abnormalities are associated with disorders
leading to monoclonal gammopathies and abnormal FLC
levels. B-cell dysfunction has been well-described in HIV
infection
and
leads
to
the
following:
hypergammaglobulinaemia, polyclonal B-cell activation,
increased B-cell turnover, increased expression of
activation markers, increased differentiation of B-cells,
increased production of immunoglobulins, increased
abnormalities on serum protein electrophoresis and an
increased frequency of B-cell malignancies.
HIV Positive
Controls
Accepted reference interval
CD4+ (cell/mm3)
419.5
960.4
500 – 1200
(copies/ml)
9.549
Albumin (g/l)
40
43
35 – 42
IgG (g/l)
27
16
10 – 23
Kappa( mg/l)
38
14
3.3 – 19.4
Lambda ( mg/l)
39
18
5.7 – 29.3
FLC Ratio
1.02
0.77
0.3 – 1.2
However, to date, only one publication describes FLC
levels in HIV infection. Anti-retroviral therapy (ART) can
reverse some of the B-cell abnormalities; therefore this
is an important population to study as they have not yet
received ART.
VARIABLES
Aim
To determine the FLC levels and / ratio in HIV positive
subjects not on ART
Methods
We determined serum albumin, IgG, CD4+ counts, viral
loads, and  and  FLC levels on 72 newly diagnosed HIV
positive and 42 HIV negative subjects. FLC levels were
determined nephelometrically on Beckman IMMAGE.
The FLC results were used to calculate a / FLC ratio.
KAPPA FLC
LAMBDA FLC
FLC RATIO
Spearman p-value
Spearman p-value
Spearman p-value
correlation
correlation
correlation
(r-value)
(r-value)
(r-value)
CD4 count
-0.62
<0.01
-0.65
<0.01
-0.23
0.02
Viral load
0.33
<0.01
0.46
<0.01
-0.05
0.70
Albumin
-0.52
<0.01
-0.41
<0.01
-0.39
<0.01
IgG
0.79
<0.01
0.79
<0.01
0.41
<0.01
HIV; LS Means
Current effect: F(1, 112)=50.668, p=<0.01 Mann-Whitney U p<0.01
Effective hypothesis decomposition
Vertical bars denote 0.95 confidence intervals
HIV; LS Means
Current effect: F(1, 112)=14.985, p=<0.01 Mann-Whitney U p<0.01
Effective hypothesis decomposition
Vertical bars denote 0.95 confidence intervals
HIV; LS Means
Current effect: F(1, 112)=39.882, p=<0.01 Mann-Whitney U p<0.01
Effective hypothesis decomposition
Vertical bars denote 0.95 confidence intervals
50
1.2
45
45
40
1.1
40
35
1.0
30
25
30
FLC ratio
Lambda
35
Kappa
These FLC results were then correlated with markers of
disease severity in HIV, namely CD4+ counts, viral loads,
IgG and albumin. CD4+ counts decrease with disease
progression. Albumin is a negative acute phase reactant
and decreases with disease progression. IgG will be
more increased with more B-cell dysfunction.
400 – 750000
25
20
0.9
0.8
20
15
Acknowledgements
We would like to thank the Binding Site for supplying
the FLC kits to perform this study and gratefully
acknowledge the contributions of Mr J Goodway for
poster layout and the following groups :
0.7
15
10
5
10
pos
neg
HIV
0.6
pos
neg
HIV
pos
neg
HIV
Conclusion
We demonstrated that FLC levels were significantly increased in a HIV positive population not yet on treatment
and correlated with markers of disease severity. This is most likely due to the well-described polyclonal
hypergammaglobulinaemia that is associated with B cell dysfunction in HIV-infection. Therefore, FLC levels may
be of value as prognostic markers in untreated HIV-infection and be useful as a monitoring tool for response to
therapies. In addition, longitudinal studies will be useful to determine if these raised FLC levels are associated
with increased risk of lymphoma.