Monocyte Lymphocyte Ratio in Tuberculosis

1. MONOCYTE LYMPHOCYTE
RATIO WITH REFERENCE TO
TUBERCULOSIS

2.  India is the highest TB burden country with World Health Organisation (WHO)
statistics giving an estimated incidence figure of 2.2 million cases of TB for
India out of a global incidence of 9.6 million cases.
 Tuberculosis is a major health problem and is the second leading cause of
death by infectious diseases after human immunodeficiency virus (HIV).
 It is much more common in low socioeconomic communities.

3.  Immune cells, both monocytes and lymphocytes have well defined role in
innate as well as acquired immunity.
 Tuberculosis is considered to be one of the most imperative cause of
monocytosis which then settles as the infection resolve.
 The results with lymphocyte count are still controversial, increasing in some
cases while decreasing in others and returning to normal with therapy.

4.  In addition, with lymphocytosis IFN-γ levels are increased at the time of
diagnosis which returns to normal with treatment.
 Lymphopenia is also another important marker of severe malnutrition along
with blood albumin levels seen in malnourished individuals, the group
considerably susceptible to TB.

5. MONOCYTES IN TUBERCULOSIS
 Monocytes are an essential component of the innate immune response that
acts as a link to the adaptive immune system through antigen presentation to
lymphocytes.
 Thus any factor that perturbs the function or relative numbers of either cell
type could potentially affect an individual’s response to infection.
 Monocytosis commonly occurs in tuberculosis.

6.  The microorganism after entering the body is engulfed by alveolar
macrophages.
 Some microorganisms escape the defense mechanisms and succeed to endure,
resulting in infection with production of chemoattractant substances which
then invites other leukocytes and results in unopposed production of
monocytes.

7.  Monocytes are the target cells for mycobacterial proliferation whereas
lymphocytes provide resistance to the spread of infection causing
mycobacterial clearance so it is reasonable to suggest that M/L ratio can also
be used as a prognostic tool in TB

8. LYMPHOCYTES IN TUBERCULOSIS
 In one study lymphopenia was seen in 50% of patients at the time of diagnosis
which later improved with treatment. None of the patient showed
lymphocytosis.
 Lymphopenia is considered to be due to accumulation of lymphocytes at the
site of infection leading to decreased number in peripheral blood.
 There are different studies available mentioning lymphocyte count in TB and
the effect of TB on lymphocyte count is still uncertain.
 Santiago and colleagues supported lymphocytosis while Okamura et al proved
lymphopenia in their study.

9. MONOCYTE LYMPHOCYTE RATIO
 To calculate the ML ratio, the absolute monocyte count was divided by the
absolute lymphocyte count.
 The ML ratio in peripheral circulation may reflect an individual’s capacity to
mount an effective immune response.
 ML ratio has been shown to correlate with inhibition of mycobacterial growth
in vitro and the risk is higher among individuals with either low or high ML
ratio.

10.  In a study conducted by Sumaira Iqbal et al
on Monocyte Lymphocyte Ratio as a
Possible Prognostic Marker in Anti Anti
tuberculous Therapy
 Found that M/L ratio in TB0, TB2 and TB4
group were 0.24 ± 0.14, 0.20 ± 0.10 and
0.19 ± 0.10 respectively.
 TBO = At the start of anti tuberculous therapy
 TB2= At the end of initiation phase
 TB3= During maintainance phase

11. In a study conducted by Jun Wang et al, on the ratio of monocytes to
lymphocytes in peripheral blood in patients diagnosed with active
tuberculosis and found that ML ratio in patients with active tuberculosis is
high in comparison with healthy donors.

12. In a study conducted by Jun Wang et al on the ratio of monocytes to lymphocytes
in peripheral blood in patients diagnosed with active tuberculosis and indicated that
ML ratio less than the 9th percentile or greater than the 25th percentile were
significant predictors for active tuberculosis.

13.  The different proportion of myeloid based or lymphoid-based hematopoietic
stem cells may underlie the peripheral difference of ML ratio.
 Therefore, it is reasonable that Mycobacterial infection may alter
hematopoietic stem cells such that the ML ratio is altered.
 The change of monocytes and lymphocytes, reflected in their ratio, may
affect patients’ ability to respond to mycobacterial infection.

14.  In order to further evaluate whether ML ratio could be affected by anti-TB
therapy, the difference between before treatment and after therapy was
analyzed.
 The results indicated that high ML ratio decreased, and low ML ratio increased
to be close to the ML ratio of healthy donors.

16.  It suggested that ML ratio of patients may be changed with anti-TB therapy
and the alteration of ML ratio may also reflect the effectiveness and phase of
therapy.
 This study had several limitations as the eligible patients represented a
fraction of the patients diagnosed with active tuberculosis during the study
period, raising a concern for a selection bias.

17.  The MLR has been suggested to be associated with survival in patients with
malignant lymphomas and many solid tumors, such as
 Head and neck, breast, lung, esophageal, gastric, colorectal , pancreatic,
bladder, and cervical cancers.
 A high MLR was associated with poor results in previous reports, and the MLR
can be considered to be a potential surrogate biomarker in various cancers.

18.  Although the mechanisms of the association between a higher MLR and a
poorer prognosis have not been fully clarified, the MLR may reflect the
balance between the
 “favorable role of lymphocytes and the unfavorable effect of monocytes
with respect to cancer progression.”

19.  M/L ratio increases with chronic inflammations including TB which then
settles under the effect of anti tuberculous therapy.
 M/L ratio can be considered as an independent prognostic marker and
predictor of anti tuberculous treatment.
 M/L ratio has already been used as a prognostic marker in various malignances
including colon cancer, non-Hodgkin lymphoma and multiple myeloma.

20. OTHER PROGNOSTIC MARKERS
 C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) has been
commonly used for monitoring the treatment
 Other time consuming markers are Interleukin (IL) -10, IL-13, and other
immune markers but a single specific marker for monitoring of tuberculosis is
yet to be found.

21. THANK YOU