C-Reactive Protein and Soluble Intercellular Adhesion Molecule-1 in Helicobacter Pylori Infection Associated with

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Indian Journal of Public Health Research DOI Number: 10.37506/v11/i1/2020/ijphrd/194091
                                                                              & Development, January 2020, Vol. 11, No. 01 1683

    C-Reactive Protein and Soluble Intercellular Adhesion
   Molecule-1 in Helicobacter Pylori Infection Associated with
                     Chronic Renal Failure

                            Sahlah Kh. Abbas1, Najdat B. Mahdi2, Aseel Sh.Abdulla3
  1Department   of Biology, Collage of Science, 2Department of Biology, Collage of Education for Pure Sciences,
                   3
                     Environmental Research Unit, Collage of Science, University of Kirkuk, Iraq

                                                        Abstract
    Background: Patients with chronic renal failure have higher risk of Helicobacter pylori infectionas a
    result of chronic systemic and local circulatory failure, hypergastrinemia, high ammonia and the developed
    inflammation. Infection with Helicobacter pylori may lead to changes in some inflammatory markers. This
    study was aimed to investigate the influence of Helicobacter pylori infection onserum levels of C-reactive
    protein, soluble intercellular adhesion molecule-1 and lipid profile in Iraqi patients with chronic renal failure.

    Method: The study included 56 individuals who attended Kirkuk General Hospital to receive hemodialysis.
    They were divided into 2 groups; chronic renal failure patients with Helicobacter pylori seropositive (Group 1)
    and seronegative (Group 2) infections. Group 3 included 30 apparently healthy subjects as control group
    who were age- and gender-matched to patients groups. Lipid profiles were measured by enzymatic analytical
    chemistry. C-reactive protein, soluble intercellular adhesion molecule-1 and anti Helicobacterpylori IgG
    were assayed by ELISA technique.

    Results: When we compared chronic renal failure patients with Helicobacter pylori seropositive and
    seronegative infections to healthy normal renal function subjects,we found significant increase in C-reactive
    protein and soluble intracellular adhesion molecule-1 levels, whilst there were no significant differences
    between Helicobacter pylori seropositive and seronegative chronic renal failure patients (P>0.05). In this
    regard, lipid profile results showed a significant reduction in total cholesterol and High density lipoprotein
    levels inpatients. Also, linear correlation was found between soluble intracellular adhesion molecule-1 level
    and creatinine.

    Conclusion: The result of this study concluded that impaired renal function is associated with endothelial
    dysfunction and raised inflammatory activity as assessed by serum levels of soluble intracellular adhesion
    molecule-1 and C-reactive protein as well as urea and creatinine levels, yet these patients had reduction in
    lipid profile as a result of malnutrition. However, Helicobacter pylori infection didn’t induce significant
    changes in the levels ofstudied parameters which are considered important risk factors for atherosclerosis.

    Keyword: Chronic renal failure, Helicobacter pylori infection, C-reactive protein, Soluble Inter cellular
    Adhesion Molecule-1, lipid profile.

                     Introduction                               abdominal symptoms, diarrhea, hemorrhage and
                                                                constipation[1,2]. Helicobacterpylori (H. pylori) are Gram-
    Chronic renal failure (CRF) patients receiving
                                                                negative bacteria transmitted from human to human and
hemodialysis (HD) treatment for long period are
                                                                colonize the stomach. Its infection is associated with the
often encounter to heart failure, hypertension, renal
                                                                development of gastrointestinal disease such as peptic
anemia, parathyroid-related disease and suffer from
                                                                ulcer disease (PUD), mucosa-associated lymphoid tissue
gastrointestinal troubles including peptic ulcer,
                                                                (MALT) lymphoma and gastric cancer both in patients
1684    Indian Journal of Public Health Research & Development, January 2020, Vol. 11, No. 01
with CRF receiving hemodialysis and in individuals                  -20o Cuntil the time of assessment. To determine serum
with normal renal function[3-5]. Its infection is prevalent         levels of urea, creatinine, total cholesterol (TC) and
in about 50% of the population in developed countries               high-density lipoprotein (HDL-C), we used kit from
and colonizes 70‑90% in developing countries[6].                    the British company Randox according to instructions
As a result of the increase in both of prevalence of                provided by the company. On the other hand, serum
H.pylori and their resistance to antibiotics, this bacterial        level of triglyceride was measured using the CTM (UK)
species is recognized as a high-priority pathogen by                kit, according to instructions of the supplied company.
World Health Organization in 2017[7]. Raised levels                 The level of CRP and sICAM-1 were measured with
of C-reactive protein (CRP), intercellular adhesion-1               sandwich enzyme immunoassay technique (ELISA) kits,
(ICAM-1) and dislipidemia were reported by previous                 (LABOR DIAGNOSTIKA NORD (LDN)/Germany for
studies in chronic renal failure patients with H.pylori             CRP and Mybiosource/USA for sICAM-1).To detectanti
infection[8-10]. These parameters considered as risk                H.pylori IgG, we used Trinity Biotech/Ireland ELISA
factors for cardiovascular events.-CRP is a nota specific           kit.
marker, increased level of this protein might indicate
acute inflammation and increased risk of suffering from                  Statistical Analyses: All data were given as
a heart attack[11,12]. Previous results reported significant        mean±SD and analyzed using Statistical Package for
association of H. pylori infection with elevated serum              Social Sciences (SPSS, version 13). The differences
CRP[13,14]. In addition, expression of ICAM-1 was higher            between means,with regard to biochemical tests, were
in atherosclerotic plaques containing H. pylori infection           assessed by Duncan’s test, while differences between
than in those without it [15] as well as hemodialysis               means of CRP and sICAM-1 were assessed by student’s
treatment enhances elevation of ICAM-1 level in chronic             t-test. Pearson rank correlation was used to detect the
renal failure patients[16]. Accordingly, the present study          correlation between parameters. The probability value
was aimed to investigate the influence of H.pylori                  less than 0.05 considered statistically significant.
infection on serum levels of CRP, soluble ICAM-1 and
lipid profile in chronic renal failure patients.
                                                                                                Results
                                                                         Out of the 125 patients with CRF recruited in current
                 Materials and Method                               study, 26(21%) were seropositive and 99(79%) were
    This study was performed on 86 subjects divided                 seronegative to H.pylori infection. Out of 26 seropositive
into three groups. Group 1 included 26CRF patients                  patients, 17 were males whose age ranged between 30
with H.pylori seropositive infection, their age range was           and 79 years and 9 were females whose age ranged
30-79 years. Group 2 included 30 CRF with H.pylori                  between 46 and 70 years. The study showed statistically
seronegative, their age range was 46-70 years. Group 3              significant increase in serum levels of urea and creatinine
served as control group; included 30 apparently healthy             in both group 1 and group 2 patients compared to control
individual who were age- and gender-matched to patient              group. On the other hand, there was significant decrease
groups. Allpatients were recruited for dialysis unit at             in serum levels of TC and HDL-Cin patients rather than
Kirkuk General Hospital during the period from October              control group. Also, LDL level significantly decreased
2018 to March 2019. Five milliliters of venous blood                in H.pylori seropositive infection rather than control
sample was collected from each participant, centrifuged             group. Serum levels of TG and VLDL were approximate
for 10 minutes at 1000rpm, then frozen and stored at                among studied groups (Table 1).

                Table 1: Comparison between studied groups with regard to biochemical parameters

 Parameter                              Group 1 (n=26)                    Group 2 (n=30)                  Group 3 (n=30)
 Urea (mg/dl)                             124.5A±6.11                       118.83A±4.33                    26.5B±1.32
 Creatinine(mg/dl)                        3.89A±0.05                        5.518A±0.04                     0.62B±0.02
 Cholesterol(mg/dl)                      136.87B±6.11                       142.72B±7.65                    182A±3.51
                                                   A                              A
 Triglycerides(mg/dl)                    134.12 ±40.7                       106.75 ±8.22                   123.85A±7.2
 HDL-C (mg/dl)                            33.37B±2.04                         31B±0.71                     41.45A±1.22
                                               B                                 AB
 LDL(mg/dl)                               80.8 ±4.53                        91.07 ±5.54                    118.2A±3.33
 VLDL(mg/dl)                              23.97A±1.57                        21.97A±1.4                    24.91A±0.05
Indian Journal of Public Health Research & Development, January 2020, Vol. 11, No. 01   1685
    Data were presented as mean ± SD. Different letters          control group. Also, this study revealed that serum levels
represented a significant difference (P≤ 0.05) between           of CRP were markedly increased in H.pylori seropositive
means of rows, while similar letters referred to non-            patients than H.pylori seronegative patients. However,
significant difference (P≥0.05) between these means.             they were not statistically significance (Table 2 and
                                                                 Figure 1).
    Using ELISA technique, serum level of CRP was
significantly increased in groups 1 and 2 compared to

                          Table 2: Comparison of serum CRP levels between study groups

 Study group (Serum CRP level in ng/ml)                                               P value
 Group 1 (9892.5±722.21                                                              P>0.05**                 P0.05*                                               P0.05*                                             P< 0.0001***
 Group3(47.2±1.4)                                        P< 0.01*                  P< 0.0001**
*Comparison between group 1 and other groups. **Comparison between Group 2 and other groups. *** Comparison between Group 3
and other groups.

 Figure 1: Mean serum CRP levels (ng/ml) in study
                                                                    Figure 2: Mean serum levels (ng/ml) of sICAM-1
                     groups.
                                                                                among studied groups.

    When we studied the correlation between serum                patients by using Pearson rank correlation, data showed
levels of CRP, sICAM-1 and urea, creatinine, TC,                 significant direct correlation between sICAM-1 level
HDL-C, LDL-C and VLDL-CinH.pylori seropositive                   and creatinine level (r= 0.859, P=0.013; Table 4).
1686     Indian Journal of Public Health Research & Development, January 2020, Vol. 11, No. 01
   Table 4: Correlation and predictive value for the parameters in CRF patients with H.pylori seropositive
                                                   infection

                                                         CRP                                              sICAM-1
 Parameter
                                              r                    P- Value                        r                P-Value
 Urea (mg/dl)                               0.138                    0.769                       -0.172              0.713
 Creatinine (mg/dl)                        -0.112                    0.811                       0.859               0.013
 Cholesterol (mg/dl)                       -0.274                    0.551                       -0.120              0.797
 Triglycerides (mg/dl)                      0.220                    0.635                       0.422               0.346
 HDL-C (mg/dl)                             -0.234                    0.613                       -0.449              0.313
 LDL (mg/dl)                               -0.293                    0.524                       -0.220              0.636
 VLDL (mg/dl)                              -0.176                    0.705                       0.236               0.610
 sICAM-1 (ng/ml)                           -0.271                    0.557                         -                   -
r: Correlation coefficient

     Discussion Chronic inflammation triggers release                study[25]associated the raised concentration of CRP
of proinflammatory cytokine such as IL-1,IL-6 and                    with other conditions such as increased age, smoking,
TNF-α,which contribute to atherosclerosis events and                 H. pylori and symptoms of chronic bronchitis as well as
endothelial dysfunction[17,18]. Chronic inflammationis a             Chlamydia pneumonia infection and BMI.
common feature of end-stage renal disease[19] as well as
chronic H. pylori infectionmay lead to chronic gastritis,                 In our study we found that chronic renal patients
gastric cancer and peptic ulcer. Also, alteration in lipid           with H.pylori seropositive and seronegative infections
profile is another consequence to systemic inflammatory              had significantly higher levels of sICAM-1 than healthy
status[20].                                                          controls. This finding was similar to[11] who reported
                                                                     that the expression of adhesion molecule (sICAM-1)
     Our result denoted that serum levels of total                   was elevated in plaques containing H.pylori than in those
cholesterol (TC), low density lipoprotein (LDL)                      without it and mentioned that H.pylori was detected in
and high density lipoprotein(HDL) were decreased                     atherosclerotic plaque in addition to gastric mucosa [15,25].
significantly in systemic circulation of groups 1 and 2              In addition, hemconcentration of sICAM-1 in chronic
patients compared to control group, while there were no              renal failure may be due to shedding of this molecule
change in serum levels of triglycerides (TG) and very                from surface of lymphocytes and monocytes and
low density lipoprotein(VLDL). A previous study[20]                  releasing it into circulation stimulated by hemodialysis
reported that H.pylori infection is associated with high             membrane[26] as well as decreased elimination by the
TC, LDL and TG, yet lower HDL-C serum levels.                        impaired kidney which plays an important role in their
Another study[21] reported an increase in TG serum level             catabolism[27]. Elevated serum levels of soluble ICAM-
in H.pylori patients. Decreases in serum levels of lipid             1 were directly correlated with the level of creatinine
variables in chronic renal failure patients may be due               reflecting glomerular filtration rate (GFR). Renal
to malnutrition as a result of multiple pathophysiologic             dysfunction diminishes the ability to filter creatinine and
alterations including decreased appetite and nutrient                serum creatinine rises. The glomerular filtration rate is
intake, metabolic imbalances, hormonal derangements,                 clinically important because it is a measure of kidney
increased catabolism, inflammationand dialysis-related               function.
abnormalities[22,23].
                                                                                                 Conclusion
     Our results showed a statistically significant increase
in CRP level, which indicated an acute inflammatory                      The results of this study concluded that impaired
status. The production of this proteinis regulated by                renal function is associated with endothelial dysfunction
proinflammatory cytokine, such as IL-6, this cytokine                and raised inflammatory activity as assessed by serum
is modified by other cytokines, growth factors and                   levels of sICAM-1 and CRP. Also, these patients had
hormones such as insulin and cortisol[24]. Another                   reduction in lipid profile as a result of malnutrition.
Indian Journal of Public Health Research & Development, January 2020, Vol. 11, No. 01   1687
Moreover, there was significant positive association           8.    Chiurchiù V, Leuti A, Maccarrone M.Bioactive
between the levels of ICAM-1 and creatinine. In contrast             Lipids and Chronic Inflammation: Managing the
H.pylori infection showed no significant differences in              Fire Within. Front Immunol 2018; 9:38.
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scientific research ministries in Iraq.                        11. Oshima T, Ozono R, Yano Y, Oishi Y, Teragawa
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    Conflict of Interest: The authors declare that they            of Helicobacter pylori infection with systemic
have no conflict of interest.                                      inflammation and endothelial dysfunction in
     Funding: Self-funding.                                        healthy male subjects. J Am Coll Cardiol 2005;-
                                                                   45(8):1219‑22.
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