Indian Pediatr 2014;51: 1000-1002
Immunoglobulin Levels and CD4 / CD8 Counts in
PP Kadam, MV Manglani, SM Sharma, RA Sharma and MS
From Department of Pediatrics, Division of Pediatric
Hematology-Oncology, Lokmanya Tilak Municipal Medical College and
General Hospital, Sion, Mumbai, India.
Correspondence to: Dr Mamta Manglani, Professor &
Head, Pediatrics, Chief, Division of Hematology-Oncology, Lokmanya Tilak
Municipal Medical College & General Hospital, Sion, Mumbai 400 022,
Received: March 13, 2014;
Initial review: June 19, 2014;
Accepted: October 01, 2014.
- thalassemic patients, and correlated them with anti-HIV,
anti-HCV and HBsAg status, number of transfusions, iron overload and
splenectomy. Methods: Patients with acute or chronic diseases
(except HIV, Hepatitis B and C), on immunosuppressive drugs or
vaccinated within one month prior to study were excluded. CD4, CD8
counts and serum Immunoglobulins were documented. Results:
Increasing transfusions led to higher IgA and IgM as well as a
decline in CD4 and CD8 levels. Higher ferritin correlated with high
IgM. CD4, CD8 and IgA were significantly higher in splenectomized
subjects. HCV correlated significantly with lower IgA values.
Conclusion: Higher transfusion requirement, iron
overload, splenectomy and HCV infection correlated with alterations
in different immunological parameters.
Objective: This cross-sectional study determined the CD4, CD8
counts and serum immunoglobulins in transfusion dependent
Keywords: Immunity, Iron, Transfusion.
dvances in transfusion
regimens and iron chelation therapy have improved the quality of life as
well as life-expectancy of transfusion-dependent thalassemics. Never-theless,
this has led to disclosure of several newer complications such as
immunological alterations causing increased infections. Several studies
have found infections to be the second commonest cause of death after
heart failure in thalassemia [1-3]. This has been attributed to various
immunological abnormalities. Factors that might lead to these
abnormalities include iron-overload, splenectomy, Desferioxamine,
exposure to allogenic antigens in blood, immunosuppressive viruses, and
liver damage following hepatitis. The disease itself does not seem
responsible as non-transfusion dependent thalassemics do not exhibit
similar immunologic changes . The current study was therefore
designed to study the CD4 and CD8 counts, and immunoglobulin levels in
multi-transfused patients with b–thalassemia.
This was a cross-sectional, observational study
conducted at a tertiary care hospital between July 2010 and June 2011.
All patients with transfusion-dependent
were included. Those with any acute/chronic illness or infection
(excluding HIV, Hepatitis B and C) and who had received any vaccinations
or immuno-suppressive medications including steroids, hydroxyurea etc.
during one month prior to enrolment were excluded.
History and examination including number of
transfusions, chelation, signs of iron overload, and splenectomy-status
was noted. Apart from routine investigations, anti-HIV antibody, HBsAg,
anti-HCV antibody and serum ferritin were performed. Mean
pre-transfusion hemoglobin, and yearly packed red blood cell requirement
were calculated. CD4, CD8 levels and Serum IgG, IgM, IgA levels were
analyzed using standard methods at National Institute of
Immunohaematology (NIIH), ICMR, Parel, Mumbai. Institutional Review
Board approval was obtained.
The CD4, CD8 and immunoglobulin levels were compared
with age-matched normal values [5,6]. Statistical analysis was done
using Chi-square test, Fisher exact test, Student’s t-test, correlation
co-efficient and linear regression models.
Data from total of 100 patients (60 males) were
analyzed. The mean (SD) age of the subjects was 10.9 (5) years.
Nineteen, 56 and 25 patients had low, normal and high CD4 values,
respectively. CD8 counts were normal in 69, low in 11, and
high (abnormal) in 20 subjects. IgG levels were normal in 48 patients
and high in 51 patients. Only 1 subject had low values. Ninety-three
subjects had normal IgA levels while 4 and 3 subjects had low and high
values, respectively. Ninety-five subjects had normal IgM levels. The
remaining five had a high value. The mean (SD) number of transfusions
received was 155.8 (81.44). There was a significant positive correlation
between number of transfusions and IgA (r = 0.2985) and IgM (r =
0.2637). Serum ferritin was available in 69 patients. The mean (SD)
serum ferritin level was 4296.83 (2576.35) ng/mL. We noted increasing
IgG (P>0.05) and IgM levels with increasing serum ferritin
levels. The mean (SD) packed RBC requirement in the subjects was 171.9
(33.38) cc/kg/year. Results depicted a significant decline in CD4 (r = -
0.379) and CD8 (r = - 0.3659) counts with higher RBC requirement.
Two subjects each were anti-HIV and HBsAg-positive,
whereas 34 patients were anti-HCV positive. A significant decrease in
IgA levels was noted in those with anti-HCV antibodies (P =
0.048). Ten children were splenectomized. As shown in Table I,
the CD4 (P< 0.0001), CD8 (P < 0.0001) and IgA (P =
0.01) levels were significantly higher in splenectomized subjects.
TABLE I CD4, CD8, IgG, IgA and IgM Values in Splenectomized vs Non-Splenectomized Children
All values in mean (SD); *P<0.005.
We found that higher number of transfusions increased
the IgA and IgM significantly, whereas iron overload increased the IgM
significantly. Low CD4 and high CD8 counts (abnormal) were observed in
those requiring higher amount of packed red cells. CD4, CD8 and IgA were
significantly higher in spenectomized patients. Low IgA levels were
noted in those with anti-HCV antibodies.
The present study had some limitations. We evaluated
only selected immunological parameters. Neutrophil functions, other
lymphocyte subsets, IgD and IgE were not done. Moreover, serum ferritin
was done only in 69 subjects.
Interestingly, low CD4 counts were observed only in
19 subjects, with high CD8 values in 20 subjects. This was contrary to
published studies [7,8]. Twenty five of our subjects had unexpectedly
high CD4 values. This has been described in a study by Nualart, et al.
 to be due to functionally defective cells. Similarly, low CD8 count
was another surprising finding. A description of L CD8 phenotype,
wherein intrinsically these persons have a low CD8 count, has been
described , and was likely the case here.
Evaluation of serum immunoglobulins revealed results
differing from most previous studies, which have shown elevated levels
of IgG, IgM and IgA . Similar trend has been observed in other
recent studies also . This could be due to better chelation as well
as leuco-depleted red cell transfusions currently in use for thalassemic
patients. With increasing number of transfusions, there was an increase
in the levels of immunoglobulins,. It has been postulated that donor
alloantigens lead to development of alloantibodies to the patients’
RBCs, leading to conformational changes on the epitope of RBC antigens,
thereby stimulating the formation of autoantibodies. Additionally,
leucocyte antigens are an important source of immune stimulation
[13-15]. Leuco-depletion, preferably pre-storage, is therefore
imperative to reduce allo and autoimmunization in patients with
thalassemia. Significantly higher CD4, CD8 and IgA levels in
splenectomized subjects, as seen in this study have also been reported
In conclusion, with appropriate transfusion and
chelation therapy, the immunological alterations in
transfusion-dependent children with thalassemia can be minimized,
thereby preventing morbidity and mortality due to infections.
Acknowledgements: Dean, Dr Avinash Supe for
permitting us to publish this work. Dr. Manisha Madkaikar and Snehal
Mhatre, Senior Scientists, NIIH, Parel, Mumbai, for performing the
various tests at NIIH, ICMR, Mumbai.
Contributors: PPK: conducted the study and
drafted the manuscript; MVM: conceptualized and designed the study,
guided through the study and finalized the manuscript with important
intellectual inputs. She will act as guarantor for the study; SMS:
helped in collecting and analysing data as well as drafting of
manuscript; RAS: helped in designing the study and finalizing the
manuscript; MSS: statistical analysis, interpretation of the data and
revision of manuscript. The final manuscript was approved by all
Funding: None; Competing interests: None
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