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Re: Normal of CD4 and CD8 lymphocyte subsets in healthy indian

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Dear Forum members,

According to Uppal SS, Verma S, Dhot PS (2003 Mar;52B(1):32-36) “When compared

with other published series, the CD4 and CD8 values in healthy Indians were no

different from those reported in the West”

According to Ramalingam S, Kannangai R, Zachariah A, Mathai D, Abraham C. (2001

Nov-Dec;14(6):335-9) “The mean CD4 count among normal south Indians is

significantly lower than that in the western population and parallels that of

the Chinese. When categorized based on the CDC classification system, the mean

CD4 count of HIV-infected individuals was lower”

Enclosed are references related to CD4 cell counts among normal (healthy)

Indians. Please go to www.medscape.com for complete articles. Some of these

article are available online, but some need to be obtained from the hard copies

of the respective journals

Dr. Sai Subhasree Raghavan

Columbia University and SAATHII

E-mail: <ssr12@...>

-----------------------------------------

1. Normal values of CD4 and CD8 lymphocyte subsets in healthy indian

adults and the effects of sex, age, ethnicity, and smoking. Uppal SS, Verma S,

Dhot PS. Cytometry 2003 Mar;52B(1):32-36

2. CD4 counts of normal and HIV-infected south Indian adults: do we need a new

staging system? Ramalingam S, Kannangai R, Zachariah A, Mathai D, Abraham C.

Christian Medical College and Hospital, Vellore, Tamil Nadu, India. Natl Med J

India. 2001 Nov-Dec;14(6):335-9

3. Peripheral CD4+/CD8+ T-lymphocyte counts estimated by an immunocapture method

in the normal healthy south Indian adults and HIV seropositive individuals. J

Clin Virol. 2000 Aug;17(2):101-8. Kannangai R, Prakash KJ, Ramalingam S, Abraham

OC, Mathews KP, Jesudason MV, Sridharan G. Department of Clinical Virology,

Christian Medical College Hospital, Vellore, India.

4. Immunologic profiles of HIV-infected and uninfected commercial sex workers in

the Vellore region of Southern India. Babu PG, Pramilabai A, Sripriya G,

Damodharan S, TJ.Acquir Immune Defic Syndr Hum Retrovirol. 1997 Dec

15;16(5):357-61.

___________________

1. Normal values of CD4 and CD8 lymphocyte subsets in healthy indian

adults and the effects of sex, age, ethnicity, and smoking. Cytometry 2003

Mar;52B(1):32-36 Uppal SS, Verma S, Dhot PS. Clinical Immunology Center and

Laboratory, Command Hospital, Pune, India; and Department of Medicine, Faculty

of Medicine, Kuwait University, Kuwait.

BACKGROUND: Information on lymphocyte populations (T, B, and natural

killer cells) and subpopulations (CD4 and CD8) in India is generally lacking.

Measurement of T-cell subsets is important in India for evaluating disease stage

and progression in individuals with the human immunodeficiency virus (HIV).

Hence, this study was conducted to provide normal ranges of absolute and

percentage values of CD4 and CD8 T-lymphocyte subsets and the ratio of CD4 to

CD8 in normal Indian adults. METHODS: Flow cytometric analysis (EPICS-XL) was

used to determine the range of T-lymphocyte subpopulations in normal Indian

blood donors at Command Hospital and the Armed Forces Medical College, Pune,

India. The reference population consisted of

94 healthy HIV-seronegative blood donors. T-lymphocyte subsets were analyzed

with two-color immunophenotyping of peripheral blood lymphocytes with the use of

a lysed whole-blood technique and enumerated. RESULTS: For normal values of

various blood components, we found mean values of 2114 cells/ & mgr;l for total

lymphocytes, 865 cells/ & mgr;l (40.2%) for CD4(+) lymphocytes, 552 cells/ & mgr;l

(31.3%) for CD8(+) lymphocytes, and 1.7 for the CD4:CD8 ratio. The 95%

confidence intervals for the same parameters were 1115-4009 cells/ & mgr;l,

430-1740 cells/ & mgr;l (30.75-49.60%), 218-1396 cells/ & mgr;l (20.06-42.52%), and

0.39-3.02 respectively. Females had significantly higher CD4 counts (P < 0.05),

percentage of CD4 lymphocytes (P < 0.01), and CD4:CD8 ratio (P < 0.01). Males

had a significantly higher percentage of CD8 lymphocytes (P <0.01). They also

had higher CD8 counts that did not reach significance. Age, ethnicity

(Dravidian versus Aryan), smoking, alcohol consumption, and the interval between

drawing the blood sample and its analysis were factors that did not produce

statistically significant differences in the T-cell subsets studied.

CONCLUSIONS: When compared with other published series, the CD4 and CD8 values

in healthy Indians were no different from those reported in the West. These

observations have important clinical implications for the use of T-lymphocyte

subset measurements in India, especially in the management of HIV

infection. The normal ranges established by this study can be used as a

reference for decisions made in clinical practice.

__________________________________

2. CD4 counts of normal and HIV-infected south Indian adults: do we need a new

staging system? Ramalingam S, Kannangai R, Zachariah A, Mathai D, Abraham C.

Christian Medical College and Hospital, Vellore, Tamil Nadu, India. Natl Med J

India. 2001 Nov-Dec;14(6):335-9

BACKGROUND: The normal range of CD4 lymphocyte count varies among different

ethnic groups. In populations with CD4 counts inherently lower than in the est,

the Centers for Disease Control and Prevention (CDC) classification system of

HIV-infected individuals may not be appropriate. No such criterion is currently

available for ethnic south Indian HIV-infected individuals. We undertook this

study to assess the applicability of the western case definition to south Indian

HIV patients.

METHODS: The CD4 counts of 104 normal and 79 HIV-infected south Indian adults

were estimated by flowcytometry. The mean CD4 counts were estimated and compared

between CDC groups A, B and C and controls. Receiver operator characteristics

curves were generated to determine the cut-off that correlated best with

clinical staging for this population.

RESULTS: The mean CD4 and CD8 cell counts/microl and the CD4/CD8 ratio of the

control group were 799.0, 919.6 and 0.94, respectively. For CDC groups A, B and

C, the mean CD4 counts/microl were 454.4, 254.4 and 168; mean CD8 counts/microl

were 1156, 1070.9 and 1191.3; and mean CD4/CD8 ratios were 0.44, 0.25 and 0.15,

respectively.

CONCLUSION: The mean CD4 count among normal south Indians is significantly lower

than that in the western population and parallels that of the Chinese. When

categorized based on the CDC classification system, the mean CD4 count of

HIV-infected individuals was lower. Categories of CD4 counts > 300, 81-300 and <

or =80 cells/microl and CD4% > 14, 7-14 and < or = 6

correlate better with disease progression among HIV-infected individuals. A

longitudinal study is required before guidelines for the

Indian population can be devised.

_____________________

3. Peripheral CD4+/CD8+ T-lymphocyte counts estimated by an immunocapture

method in the normal healthy south Indian adults and HIV seropositive

individuals.

J Clin Virol. 2000 Aug;17(2):101-8. Kannangai R, Prakash KJ, Ramalingam S,

Abraham OC, Mathews KP, Jesudason MV, Sridharan G. Department of Clinical

Virology, Christian Medical College Hospital, Vellore, India.

BACKGROUND: Flow cytometry is the standard method for the estimation of CD4/CD8

counts, but the high initial investment for this instrument and costly reagents

make it

unaffordable to most of the centers in a developing country like India.

OBJECTIVES: To evaluate the feasibility of an alternate system for the

estimation of CD4 and CD8 counts in normal south Indian adults and validate the

usefulness of this assay to monitor the counts in HIV seropositive individuals.

STUDY DESIGN: Forty-six normal healthy adults and 68 HIV seropositive

individuals both belonging to south Indian linguistic groups were enrolled in

this cross-sectional study. The HIV seropositive individuals included 54 HIV-1,

9 HIV-2 and 5 HIV 1 & 2 infected individuals serologically confirmed by one of the

commercial Immunoblot kits. The Capcellia CD4/CD8 whole blood assay, an

immuno-capture ELISA based kit from Sanofi DIAGNOSTICS Pasteur, (France) was

used with a few modifications in the procedure to measure the CD4 and CD8

counts.

RESULTS: The mean CD4 cell counts were 1048 (central 95 centile only), 746 and

424 for the normal healthy adults, asymptomatic HIV seropositives and

symptomatic HIV patients, respectively, and the mean CD8 counts were 595, 889

and 732, respectively. Statistically significant differences were observed in

the CD4 cell counts between HIV seronegative healthy adults and asymptomatic (P

< 0.001) as well as asymptomatic and symptomatic (P < 0.05) HIV infected

individuals. The mean CD4 counts of asymptomatic HIV-2 infected individuals was

significantly higher than the counts of asymptomatic HIV-1 infected individuals

(P < 0.05).

CONCLUSIONS: This is an user friendly test and can be an alternate to flow

cytometry for the estimation of peripheral T-lymphocyte subsets in developing

countries. The assay system has certain limitations inherent to ELISA

techniques.

_________________

4. Acquir Immune Defic Syndr Hum Retrovirol. 1997 Dec 15;16(5):357-61.

Immunologic profiles of HIV-infected and uninfected commercial sex workers in

the Vellore region of Southern India. Babu PG, Pramilabai A, Sripriya G,

Damodharan S, TJ. Retrovirus Laboratory, Department of Clinical Virology,

Christian Medical College Hospital, Vellore, India.

Female commercial sex workers (CSW) play a major role in the transmission of HIV

infection in India. Their immunology has not been characterized. To determine

HIV-related immunologic changes and establish baseline data for CSW, blood cell

counts and serum immunoglobulin levels of 35 HIV-positive, asymptomatic CSW; 37

HIV-negative CSW, and 35 age-matched, non-CSW, healthy women controls were

compared. The CSW, irrespective of their HIV status, had abnormalities that

included high eosinophil, lymphocyte, and CD8 counts and low CD4:CD8 ratios.

The only significant difference between the HIV-positive and HIV-negative CSW

was in their neutrophil and CD8 counts (p < 0.05, ANOVA). Compared with normal

controls, the CSW had significantly elevated serum IgG, IgA, and IgM levels;

however, no significant difference was shown between CSW who tested positive for

HIV and those who did not. These results suggest that the CSW of Vellore region

in Southern India have hyperimmunoglobulinemia irrespective of their HIV status

and thus highlight the need to use appropriate controls when immunologic

evaluation studies are done.

PIP: As part of India's National AIDS Surveillance Program, blood cell counts

and serum immunoglobulin (Ig) levels were compared in 35 asymptomatic

HIV-infected commercial sex workers (CSWs), 37 HIV-negative CSWs, and 35

age-matched, healthy, non-CSW controls. Cases and controls were residents of

southern India's Vellore region. All CSWs, regardless of HIV status, had had

repeated unprotected sex with 3-10 clients per night for a period of 5 or more

years and had been treated at least 3 times for sexually transmitted diseases

(STDs) in the past 5 years. The frequencies of the most common STDs--genital

ulcers, genital warts, syphilis, and gonorrhea--were similar IV-negative and

HIV-positive CSWs. All CSWs had significantly higher levels of IgG, IgA, and IgM

than non-CSW controls, but there were no significant differences in Ig levels

between the two groups of CSWs. The only significant difference between

HIV-positive and HIV-negative CSWs was in their neutrophil and CD8 counts.

When compared to healthy controls, HIV-infected CSWs had significantly lower

neutrophil counts and CD4:CD8 ratios and significantly higher eosinophil,

lymphocyte, and CD8 cell counts. HIV-negative CSWs had significantly higher

eosinophil and lymphocyte counts and lower CD4:CD8 ratios than healthy controls.

The abnormal immunologic profile detected in HIV-negative as well as

HIV-positive CSWs suggests that stimuli other than HIV infection are responsible

for CSWs' hyperimmunoglobulinemia. These findings further highlight the

importance of using appropriate controls in immunologic evaluation studies.

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