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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 2  |  Issue : 3  |  Page : 203-207

High C-reactive proteins levels, rheumatoid anemia, alpha-1 globulin deficiency, and hypergammaglobulinemia in rheumatoid arthritis patients from yaounde, Cameroon


1 Department of Clinical Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon
2 Center for Study and Control of Communicable Diseases, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaounde, Cameroon
3 Department of Military Health, Military Health Research Center, Yaounde, Cameroon
4 Department of Biochemistry, Faculty of Science, University of Yaounde I, Yaounde, Cameroon
5 Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon
6 Department of Biochemistry, Faculty of Science, University of Bamenda, Bamenda, Cameroon

Date of Web Publication6-Sep-2018

Correspondence Address:
Christopher Tume
Faculty of Science, University of Bamenda, PO Box 1114 Yaounde
Cameroon
Etienne Philemon Atabonkeng
Faculty of Science, University of Dschang, Dschang
Cameroon
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_91_18

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  Abstract 


Background: Rheumatoid arthritis (RA) is an autoantibodies-mediated disease affecting 0.5%–1% of the population worldwide. The present study was designed to investigate variations of protein profiles and hematological parameters of patients in Yaounde Central Hospital. Methods: The study was conducted from January to November 2017. RA cases were recruited based on the identification of established diagnosis from registers of patients of participating rheumatologists. Healthy volunteers visiting the hospital were also included as a control population. All participants were aged 15 years and above. Whole blood collected from each participant was assayed for hematological parameters. In addition, serum from each participant was assayed for the level of C-reactive proteins (CRPs) using a plate agglutination technique whereas plasma was used for protein profile through a conventional electrophoretic migration of proteins on cellulose acetate gel. Results: Overall, 22 RA patients and 10 controls were recruited and consisted, respectively, in 5 males and 17 females and 2 males and 8 females. Our study revealed that 59.09% (13/22) of patients presented high levels of CRP compared to 10% in the control group. The mean value of red blood cells was 4.38 × 106/μl and 4.698 × 106/μl, respectively, in the RA and the control groups. The mean hemoglobin value was significantly reduced in the RA group (11.07 mg/dl vs. 12.73 mg/dl, P = 0.0192), thus revealing anemia in patients. Nearly 54.5% of patients presented hypoalbuminemia compared to 20% in the control group (P = 0, 1241). A deficiency of α1-globulin was observed in 54.5% of patients while that of control group was 30%. Furthermore, 72% of the patient presented hypergammaglobulinemia compared to 30% in the control group (P = 0.0494). Conclusion: This study revealed that RA patients present a normochromic and normocytic anemia, a decreased albumin and alpha 1 globulin, a significant elevation of gamma-globulins compared to the control population.

Keywords: Extravascular manifestations, hematological parameters, protein profiles, rheumatoid arthritis


How to cite this article:
Atabonkeng EP, Marie Claire OA, Singwe-Ngandeu M, Nwobegahay J, Bonsi ST, Tsouh Fokou PV, Manfo Tsague FP, Tchakounte C, Tume C. High C-reactive proteins levels, rheumatoid anemia, alpha-1 globulin deficiency, and hypergammaglobulinemia in rheumatoid arthritis patients from yaounde, Cameroon. Biomed Biotechnol Res J 2018;2:203-7

How to cite this URL:
Atabonkeng EP, Marie Claire OA, Singwe-Ngandeu M, Nwobegahay J, Bonsi ST, Tsouh Fokou PV, Manfo Tsague FP, Tchakounte C, Tume C. High C-reactive proteins levels, rheumatoid anemia, alpha-1 globulin deficiency, and hypergammaglobulinemia in rheumatoid arthritis patients from yaounde, Cameroon. Biomed Biotechnol Res J [serial online] 2018 [cited 2019 Oct 13];2:203-7. Available from: http://www.bmbtrj.org/text.asp?2018/2/3/203/240714




  Introduction Top


Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatism that can lead to severe articular destruction. Chronic joint inflammation, and in severe cases, joint erosions in RA lead to articular cartilage and bone destruction. Many autoantibodies are described in the serum of the affected patients, and some are responsible for a long-term increase in morbidity and mortality that may be due to increased risk of infection.[1],[2] Some metabolic disorders such as diabetes mellitus, hypertension, and anemia have also been described as extraarticular manifestations of RA.[3] Several studies carried out in Caucasians came out with abnormal profile in some biological parameters in the serum and hematological parameters in RA patients. However, little is known about the impact of RA in patients in Cameroon. The present study was carried out to investigate hematological parameters, C-reactive protein (CRP) levels, and plasmatic proteins variations in RA patients from the YCH.


  Methods Top


The study was conducted from January to November 2017 and included 22 RA patients from the rheumatology service of the YCH. RA patients were recruited based on the identification of established diagnosis from medical records of participating rheumatologists and all meet the American Congress of Rheumatology criteria. Healthy visitors who accepted to be consulted by participating rheumatologists were recruited to serve as controls individuals. Visitors that present any personal or familial history of RA or autoimmune disease were not included in the study. The study protocol was approved by the Cameroon National Ethics Committee for Human Health Research, through Authorization No 2016/777/CE/CNERSH/SP of June 10, 2016. Informed consent was obtained from all adult participants while assent was obtained from minors through a parent.

After enrollment, 5 ml of blood were collected by venipuncture into an ethylenediaminetetraacetic acid-and an anticoagulated tube. The first one was used for blood cell counts using a hematological analyzer (SHENZHEN MINDRAY BC-2800 of biomedical electronics, China). Blood cells populations were compared to the normal physiological values and means values compared among the two groups. The blood parameters studied included red blood cell number (RBC), hemoglobin (HGB) level, hematocrit or packed cell volume, and mean corpuscular volume (MCV) of RBCs; white blood cell level (WBC), as well as WBC subpopulations. The plasma obtained was used for protein profiles analysis, after electrophoretic migration on a cellulose acetate gel for 50 min. Again, proteins values were compared to reference range and mean compared between the two groups. Protein profile was interpreted with reference to Szymanowicz et al. recommendations.[4] The serum obtained was used for the determination of CRP level by the plate agglutination technique (PLC kit, HELENA, France). Parameters averages were calculated and compared using the GraphPad software version 17, P < 0.05 were considered statistically significant.


  Results Top


The sociodemographic information of the population was as follows: out of the 32 participants, 22 were RA patients and 10 were controls. Furthermore, 7 were male (21, 87%) and 25 were female (78, 12%), sex ratio 3.57 in favor of females. The patient's group was made of 17 females and 5 males whereas the controls group was made of 8 females and 2 males. The mean age in the reference group was 36.90 ± 11.86 years (age range: 21–57 years) while it was 58.45 ± 14.91 years in the RA group (age range: 30–86 years). There was no significant difference among the age of participants.

C-reactive protein results profile

Our study revealed that 59.09% (13/22) of patients presented high levels of CRP (ranging from 12 to 108 mg/L) compared to 10% (1/10) (concentrations ranging from 6 to 24 mg/L) in the control group.

Hematological parameters

Red blood cells and hemoglobin profiles

The mean RBC counts were 4.38 × 106/μl and 4.698 × 106/μl of blood, respectively, in the RA group and in the control group. The mean value of HGB was 11.07 g/dl in the RA group and 12.73 g/dl in the reference group with a significant difference among the two (P = 0.0192) [Figure 1]. It was also found that the MCV was 85.40 in the RA group compared to 88.13 in the reference group and that hematocrit concentration was 37.19 and 40.50 in patients and control groups, respectively [Table 1].
Figure 1: Comparative distribution of hematological parameters between the rheumatoid arthritis patients and controls. RBC: Red blood cells, HBG: Hemoglobin, MCV: Mean corpuscular volume, WBC: White blood cells, CTLE: Controls, RA: Rheumatoid arthritis patients

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Table 1: Comparison of hematological parameters of rheumatoid patients and controls

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White blood cells and subpopulations

Evaluation of WBCs and their subpopulations revealed that the mean value of total WBCs was 4983/μL and 4219/μL, respectively, for the RA and control groups (P = 0.2341). The lymphocytes concentration was 1944/μl and 1872/μl, (P = 0.7696) while the monocyte concentration was 875.4/μl and 611.5/μl, respectively, in the RA group and the control group [Table 1]. The total WBC population appeared to be relatively higher in the pathological group than in the healthy control group. A high level of lymphocytes and monocytes was observed and could be linked to the activation of several cell lines during inflammatory processes especially in RA patients.

Basic serum proteins profiles

As shown in [Table 2], analysis of protein profiles revealed low levels of serum albumin in 54.5% of RA patients compared to 20% in the control group. Similarly, 59.1% of patients presented a low level of alpha-1 globulin (α1-globulin) compared to 40% in the reference group. Higher level of alpha-2 globulin (α2-globulin) was also identified in RA patients (27.3% vs. 10%, P = 0, 3871), while β-globulins did not vary significantly (40.9% vs. 40%). Moreover, the RA patients showed significant [Table 3] increase of gamma-globulin levels (72.7% vs 30%; P = 0.0494).
Table 2: Serum proteins values in Rheumatoid arthritis patients and Controls

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Table 3: Variations in values of serum proteins in Rheumatoid arthritis patients and controls

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  Discussion Top


This study was carried out to investigate some RA manifestations that can be detected from serum protein profiles as well as the hematological parameters of patients with RA in Yaounde, Cameroon.

C-reactive protein in rheumatoid arthritis

CRP profile analysis revealed that, although parasitic infections (intestinal parasites or malaria) can cause CRP production,[5] the latter is produced during inflammatory processes, and binds to both stimulatory receptors, FcgammaRI and FcgammaRIIa to increase phagocytosis and release of inflammatory cytokines. In RA patients, CRP is suspected to play a central role in the spread of coronary artery disease. Several reports have linked inflammation and cardiovascular risk; many studies suggest that CRP can be used as a marker for subclinical atherosclerosis and cardiovascular risk.[5] As an example, endocardial involvement which affects 40% of RA patients is related to valvulopathies resulting from the narrowing of the heart valves.[6]

Hematological in rheumatoid arthritis

Red blood cells and hemoglobin

The significant difference in HGB concentration between the two groups and the similarities in the MCV of RBC (normochromic), hematocrite (normocytosis), and mean corpuscular HGB concentration (normocytosis) suggests HGB-related anemia in the RA patients compared to the control group. Masson et al. in 2010[7] described a normochromic, normocytic, and in some cases microcytic anemia in patients suffering from chronic diseases. The latter authors described such anemia as the consequence of the abnormal metabolism of hepcidin, a hyposideremic hormone. In his normal metabolism, hepcidin regulates the transmembrane transport of iron and prevents iron exit from enterocytes, macrophages, and hepatocytes, but in RA patients, it instead inhibits the intestinal absorption of iron and its release from macrophages or hepatocytes. Indeed, inflammation which characterizes RA causes increased synthesis of hepcidin under the influence of IL-6, a decrease in the proportion of nucleated erythroid cells in bone marrow and hyposideremia [7] and a subsequent asthenia and weight loss.[7] Some other studies describe rheumatoid anemia as a consequence of the chronic gastrointestinal injury leading to low ferritinemia.[8]

White blood cells and subpopulations

This study showed a widespread of lymphocytes and monocytes linked to the activation of numerous cell lines during inflammatory processes, especially in RA patients. Sany et al. previously described RA and revealed that in about 25% of cases it is characterized by leukocytosis with polynucleosis and sometimes eosinophilia; high level of thrombocytes correlating with the inflammatory joint state.[8] Indeed, while the synovial membrane is a paucicellular structure in a normal individual, it is infiltrated by many cells populations mainly comprising CD4 + T-cells, B-cells, and macrophages that are organized into lymphoid aggregates. It has been reported that dendritic cells, monocytes/macrophages, neutrophils, and mast cells involved in the activation of the innate response are attracted to the synovial membrane by chemokines (MCP-1, MIP-1, RANTES, and IL8).[8]

Serum proteins profiles

As the main serum proteins, albumin has many physiological properties including antioxidant, anti-inflammatory, and endothelium protection against cirrhosis. A decrease in albumin synthesis is correlated with an alteration of hepatic synthesis, especially since the liver is the unique site of its synthesis.[9] Morel et al. have reported persistent hypoalbuminemia in patients with RA and attributed it as the consequence of hepatocellular insufficiency, poor nutrition, inflammatory conditions, and urinary leakage in the nephrotic or digestive syndrome.[4] It has also been found that hypoalbuminemia, especially when it is less than 22 g/l, is a predictive factor of the occurrence of infections and mortality because of its involvement on healing and repair of fractures; platelet hyperaggregability and erythrocyte morphology.[9]

Deficiency in α1-globulin is associated with liver damage in children and lungs in adults. Indeed, α-1 antitrypsin (AAT) is a protein which main function is to protect the lungs against attacks of proteases; it has been reported that AAT deficiency can be related to a genetic mutation that causes liver retention of α-1-antitrypsin with a risk of developing a liver function disorder;[7] this deficiency results in an insufficient concentration of AAT in the lungs and failure to protect them leading to pulmonary emphysema.[9],[10]

A decrease in α-2 globulin has also been described to be associated with hepatocellular insufficiency and poor nutritional states and also characterized inflammatory diseases as seen in nephrotic syndrome.[4],[8] Sany et al. revealed that RA is associated with an increase in the serum level of α2 globulins.[8]

Gamma-globulins main function is to mediate the body's natural defense by detecting and destroying pathogens. Elevated gamma-globulins in RA patients could be associated to high levels of CRP but also increase the concentration of some immunoglobulins subpopulations (IgG, IgM, IgA, IgE, and IgD). An Australian study on 33 patients with RA revealed that a significant proportion of patients had elevated serum homocysteine (hyperhomocysteinemia) levels compared to healthy individuals, coinciding with low folic acid and high concentrations of immune activation markers (TNF-R75 and neopterin immune activation markers).[11]


  Conclusion Top


Overall, this study brings out that anemia, hypoproteinemia, α-1 antitrypsin deficiency and hypergammaglobulinemia occur in RA patients. Meanwhile, further comprehensive investigations using more patients and controls are needed to get more on the impact of RA.

Limitations of the study

Few men were enrolled in the study and could not highlight the influence of gender and age groups on the changes in the biological parameters in patients with RA. In addition, a larger number of participants would have been needed to get more insights on the variations of the measured parameters.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Symmons DP, Jones MA, Scott DL, Prior P. Longterm mortality outcome in patients with rheumatoid arthritis: Early presenters continue to do well. J Rheumatol 1998;25:1072-7.  Back to cited text no. 1
    
2.
Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, et al. The mortality of rheumatoid arthritis. Arthritis Rheum 1994;37:481-94.  Back to cited text no. 2
    
3.
Doddapaneni S, Khera K, Prabhu VA, Nagappa AN, Rau NR. The impact of commodities and extra-articular manifestations in rheumatoid arthritis patients. Value Health 2013;16:A554-5.  Back to cited text no. 3
    
4.
Szymanowicz A, Cartier B, Couaillac JP, Gibaud C, Poulin G, Rivière H, et al. A proposal of ready-made interpretative comments applicable to serum protein electrophoresis. Ann Biol Clin (Paris) 2006;64:367-80.  Back to cited text no. 4
    
5.
Marnell L, Mold C, Du Clos TW. C-reactive protein: Ligands, receptors and role in inflammation. Clin Immunol 2005;117:104-11.  Back to cited text no. 5
    
6.
Daïen CI, Fesler P. Rheumatoid arthritis: A cardiovascular disease?. Ann Cardiol Angeiol (Paris) 2012;61:111-7.  Back to cited text no. 6
    
7.
Masson C. Rheumatoid anemia. Joint Bone Spine 2011;78:131-7.  Back to cited text no. 7
    
8.
Sany J. Polyarthrite Rhumatoïde de L'adulte: Conception Actuelle. France, John Libbey Eurotext; 2003.  Back to cited text no. 8
    
9.
Anaya JM, Diethelm L, Ortiz LA, Gutierrez M, Citera G, Welsh RA, et al. Pulmonary involvement in rheumatoid arthritis. Semin Arthritis Rheum 1995;24:242-54.  Back to cited text no. 9
    
10.
Fregonese L, Stolk J. Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. Orphanet J Rare Dis 2008;3:16.  Back to cited text no. 10
    
11.
Schroecksnadel K, Frick B, Kaser S, Wirleitner B, Ledochowski M, Mur E, et al. Moderate hyperhomocysteinaemia and immune activation in patients with rheumatoid arthritis. Clin Chim Acta 2003;338:157-64.  Back to cited text no. 11
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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