File Name: acute phase proteins and other systemic responses to inflammation .zip
- Acute phase proteins
- Types of acute phase reactants and their importance in vaccination (Review)
- Acute phase response
- Acute Phase Proteins: Structure and Function Relationship
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Acute phase proteins
Pulmonary tuberculosis PTB is characterized by elevated levels of acute phase proteins APPs , but their association with tuberculous lymphadenitis TBL is poorly studied. We have also examined the association of these proteins with lymph node LN size, culture grade and multiple versus single LN involvement.
APPs were not significantly associated with LN size, LN involvement and culture grade, indicating a lack of association with disease severity. TBL disease is characterized by altered levels of APPs at baseline and modulated following treatment, indicating the presence of systemic inflammation. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
The work is made available under the Creative Commons CC0 public domain dedication. Data Availability: All relevant data are within the paper and its Supporting Information file. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist. Globally, tuberculosis TB still remains a major health problem causing high morbidity and mortality [ 1 ].
Tuberculous lymphadenitis TBL is a common manifestation of extrapulmonary tuberculosis EPTB with increased prevalence in developing countries [ 2 , 3 ]. However, the mechanism of dissemination is still not clear and studies reveal that mycobacteria may mostly spread through the hematogenous route [ 4 ]. TBL diagnosis is difficult and often associated with other pathologic processes which yield inconsistent physical and laboratory findings.
A broad array of specific and non-specific immunological responses is assumed to contribute to the differential outcomes in TBL disease [ 5 , 6 ]. TBL has been associated with altered levels of certain pro-inflammatory, type 1 and type 17 cytokines in the serum or plasma [ 7 , 8 ]. These profound changes are known as acute phase responses APR and often lead to abnormal production of various plasma proteins released into the bloodstream [ 9 , 10 ].
Of note, some of these inflammatory biomarkers C reactive protein CRP , neopterin, beta 2 macroglobulin have been used for the evaluation of therapeutic monitoring, for the detection of disseminated mycobacterial disease, persistent culture positivity, radiological resolution, and specifically for the delineation of tuberculosis from malignancy [ 11 ].
Hence, discovery of reliable biomarkers without using tissue or sputum sample and with high diagnostic value would be really important in the context of EPTB diagnosis. APPs have an imperative role in scavenging extracellular hemoglobin, free radicals, iron, and are majorly considered as components of innate immunity with antibacterial and antiviral potential [ 14 , 15 ].
SAA also displays a wide variety of immune functions by inducing the synthesis of numerous cytokines and chemokines as well as activating inflammatory cascades [ 18 ]. SAA levels are also enhanced in neoplasia, injuries, trauma, infection and acute phase of inflammation [ 19 ].
C-reactive protein CRP , an established biomarker of systemic inflammation, has been described to reflect TB disease severity [ 20 ]. CRP has a vital role as an indicator of immune system activity during inflammatory responses [ 21 , 22 ]. Hp plays a crucial role in immune regulatory and inflammatory conditions by modulating the prostaglandin synthesis [ 23 ]. Hp levels are known to become altered because it is the main protein found in human plasma for hemoglobin Hb binding, which reduces the harmful physiologic and biochemical outcome of extracellular Hb [ 24 ].
Previous studies have shown the association of APPs with respect to pulmonary TB and pneumonia infection [ 15 , 25 — 29 ]. This study was conducted at NIRT, Chennai, India and the patients were recruited from hospitals and community screening in and around Chennai.
The written informed consent was obtained from all the study participants before enrolment. TBL individuals were diagnosed either by histopathology positivity or bacteriology examination consisting of GeneXpert or culture positivity for Mycobacterium tuberculosis Mtb.
Pulmonary TB individuals were selected based on the positive diagnosis for smear and culture examination for Mtb. All TBL individuals had only cervical lymphadenopathy. TST positive result was defined as an induration at the site of tuberculin inoculation of at least 10mm in diameter to minimize the false positivity due to environmental mycobacteria exposure.
Those PTB or LTB individuals with enlargement of the lymph nodes have been removed from the study as per exclusion criteria. All the individuals were HIV negative and not under any steroid treatment during the study period. All individuals were also not afflicted with any other chronic viral or bacterial infection based on medical history and physical examination. All the TBL individuals were cured from the disease which was confirmed by the disappearance of lymph node expansion analysed on X-ray and CT-scans.
The pre-and post-treatment levels were compared using the Wilcoxon signed rank test. The statistical analysis was performed using GraphPad Prism 8. The demographic details of the study individuals are listed in Table 1. We have shown our data as scatter plots with each circle representing a single individual and medians depicted with a bar. To examine the association between the systemic levels of APPs with bacterial burdens and disease severity, we examined the plasma levels of APPs and compared them with respective culture grades, lymph node size and number among TBL individuals.
As shown in Fig 2A , no significant difference was observed between the APPs in individuals with different culture grades. Similarly, none of the APPs showed any significant difference between the individuals with multiple or single lymph nodes Fig 2C.
P values were calculated using the Mann-Whitney U test. The data were examined and shown as scatter plots with each circle representing a single individual. In contrast, no significance was found between the pre and post-treatment plasma levels of SAA1 median of We have shown our data as line graphs with each line indicating a single individual. Wilcoxon signed rank test were used to measure the P values.
APPs are generic serum proteins shown to be present at higher levels in active TB disease [ 30 ]. Our findings reveal that the plasma levels of APPs were significantly altered during infection and they were modulated after the completion of ATT. This observation signifies chronic inflammation stimulated by Mtb was decreased in TBL individuals. SAA may function as an opsonin or aid in cell recruitment to the inflammatory milieu. Further, these nonspecific inflammatory markers are chiefly produced by the liver which was demonstrated in TB and also in other diseases [ 33 , 34 ].
Also, previously it has been suggested that SAA protein acts as a more profound marker of inflammation than the CRP and both were useful in elimination of infection by binding to the cell wall of microbes [ 35 ]. Herein, our observations reinforce that SAA was higher in the disease infected groups, indicating the ongoing inflammation.
This could perhaps reflect a slower kinetics in the modulation of different APPs post-treatment. Hence, the higher levels might suggest the extent of Mtb infection associated with diseased individuals. CRP has been described as a candidate biomarker for active TB disease and also in other infections as well [ 36 , 37 ].
CRP also acts as an activation marker, acute phase reactant and can be effectively used as the marker for treatment monitoring. Likewise, in our study the CRP levels were significantly modulated at the post-treatment time point. Hp recruits the neutrophils via the activated endothelial cells and platelets for free radical quenching, tissue repair and regeneration [ 22 ]. Our results corroborate the above findings; a reduction in the post-treatment plasma levels of Hp was observed when compared to pre-treatment levels.
We also examined the association of these APPs with their respective culture grade, lymph node size, multiple versus single lymph node status and bacterial burden. However, we could not find any significant association with any of these APPs with the above parameters. Some patients did exhibit increased levels of APPs following ATT, although the reason behind this needs further investigation. The altered levels of APPs could possible reflect the activation of host defence mechanism to eliminate the detrimental effects produced by TB bacteria in TBL individuals.
The authors immensely thank V. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Conclusion TBL disease is characterized by altered levels of APPs at baseline and modulated following treatment, indicating the presence of systemic inflammation.
Rottenberg, Karolinska Institutet, SWEDEN Received: October 9, ; Accepted: April 28, ; Published: May 29, This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Introduction Globally, tuberculosis TB still remains a major health problem causing high morbidity and mortality [ 1 ]. Results Study demographics The demographic details of the study individuals are listed in Table 1.
Download: PPT. Fig 1. TBL is characterised by altered plasma levels of acute phase proteins. Table 2. Table 3. APPs are not significantly associated with TBL culture grade, lymph node size, multiple versus single lymph node and bacterial burden To examine the association between the systemic levels of APPs with bacterial burdens and disease severity, we examined the plasma levels of APPs and compared them with respective culture grades, lymph node size and number among TBL individuals. Fig 2.
APPs are not associated with any significant relationship with lymph node LN culture grade, size, multiple versus single LN involvement and disease severity.
Table 4. Table 5. The fold change of pre-treatment compared to post-treatment levels of APPs. Discussion APPs are generic serum proteins shown to be present at higher levels in active TB disease [ 30 ]. Supporting information. S1 Data. Acknowledgments The authors immensely thank V. References 1.
WHO tuberculosis global tuberculosis report Tuberculous Lymphadenitis: Early Diagnosis and Intervention. J Int Oral Health. Sandhu GK. J Glob Infect Dis. Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium. Tuberculous lymphadenitis. J Assoc Phys India. Nodal tuberculosis revisited: a review. J Infect Dev Ctries.
Types of acute phase reactants and their importance in vaccination (Review)
Serum levels of acute phase reactants APR were measured in patients with rheumatoid arthritis RA and the correlations of these parameters with the disease activity score DAS28 were investigated. The study included 47 patients with RA and 50 healthy controls. Disease activity was assessed using the DAS28 score. This study indicates that serum CRP, among the various ARP tests, is the most useful biochemical marker for evaluating the disease activity of patients with RA. Rheumatoid arthritis RA is a chronic systemic disease, usually manifesting as inflammation of multiple joints.
Acute-phase proteins APPs are a class of proteins whose plasma concentrations increase positive acute-phase proteins or decrease negative acute-phase proteins in response to inflammation. This response is called the acute-phase reaction also called acute-phase response. The acute-phase reaction characteristically involves fever , acceleration of peripheral leukocytes , circulating neutrophils and their precursors. The liver responds by producing many acute-phase reactants. At the same time, the production of a number of other proteins is reduced; these proteins are, therefore, referred to as "negative" acute-phase reactants. Increased acute-phase proteins from the liver may also contribute to the promotion of sepsis.
Acute-Phase Proteins and Other Systemic Responses to Inflammation. List of authors. Cem Gabay, M.D.,; and Irving Kushner, M.D.
Acute phase response
The acute-phase response is critical to the body's ability to successfully respond to injury. It normally lasts only few days; however, if continued unchecked, the acute phase response may contribute to the development of chronic inflammatory states, tissue damage and disease. The acute phase response is typically characterized by fever and changes in vascular permeability, along with profound changes in the biosynthetic profile of various acute phase proteins APPs Hack et al.
The acute-phase response is considered part of the innate immune system, and APPs play a role in mediating such systemic effects as fever, leukocytosis, increased cortisol, decreased thyroxine, decreased serum iron, and many others. APPs can be categorized as positive increasing serum concentration or negative decreasing serum concentration. Increased production of positive acute phase proteins is a sensitive indicator of inflammation which can occur prior to the development of an inflammatory leukogram. Positive acute-phase proteins increase in plasma concentration in response to inflammation usually within days.
Ahmed, A. Jadhav, A. Hassan, Qing H. Acute phase reaction is a systemic response which usually follows a physiological condition that takes place in the beginning of an inflammatory process. This physiological change usually lasts days.
Acute Phase Proteins: Structure and Function Relationship
This is an open access article distributed under the terms of Creative Commons Attribution License. The association between the strength of the acute phase response and vaccination efficacy is of key importance to human and veterinary medicine. Proteins which are expressed in the acute phase are potential biomarkers for the diagnosis of inflammatory disease, for example, acute phase proteins APPs are indicators of successful organ transplantation and can be used to predict the ameliorative effect of cancer therapy 1 , 2. APPs are primarily synthesized in hepatocytes. The acute phase response is a spontaneous reaction triggered by disrupted homeostasis resulting from environmental disturbances 3. Acute phase reactions APRs usually stabilize quickly, after recovering from a disruption to homeostasis within a few days to weeks; however, APPs expression levels often remain elevated in long lasting infection and chronic disease states, such as cancer Classification of acute phase reactions is dependent on the change in APP concentration: A fold elevation is considered major; a fold elevation is considered moderate; and a less than 2-fold elevation is considered minor 7.
Acute phase proteins APP are proteins synthesized and released largely by hepatocytes upon the occurrence of cell damage or invasion by microorganisms. This article reviews the use of APP in feline diseases, identifying their usefulness in the clinical setting, analyzing 55 published papers. Serum amyloid A, alpha-1 acid glycoprotein, and haptoglobin are the indicators pointed out by the authors as useful in monitoring the acute inflammatory response in cats. Although, APP measurement is still not routinely used in veterinary medicine, together with clinical signs and other blood parameters, was of clinical interest and applicability in diseases such as feline infectious peritonitis, pancreatitis, renal failure, retroviral and Calicivirus infections. Although, there are commercially available kits for dosing feline APP, assay standardization aiming technical simplicity, more species specificity and with less associated costs will allow routine use in feline practice, as it is done in the human field. The acute phase response APR is an early, non-specific systemic innate immune reaction to local or systemic stimulus, which helps to heal and re-establish homeostasis and minimize tissue damage when the body is affected by trauma, infection, stress, surgery, neoplasia or inflammation GRUYS et al.
ACUTE-PHASE PROTEINS AND OTHER. SYSTEMIC RESPONSES TO. INFLAMMATION. CEM GABAY, M.D., AND IRVING KUSHNER, M.D.
Pulmonary tuberculosis PTB is characterized by elevated levels of acute phase proteins APPs , but their association with tuberculous lymphadenitis TBL is poorly studied. We have also examined the association of these proteins with lymph node LN size, culture grade and multiple versus single LN involvement. APPs were not significantly associated with LN size, LN involvement and culture grade, indicating a lack of association with disease severity. TBL disease is characterized by altered levels of APPs at baseline and modulated following treatment, indicating the presence of systemic inflammation. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.