Polymorphisms in genes involved in toll-like receptor/interferon signalling pathways have been reported previously to be associated with SLE in many populations. This study aimed to investigate the role of seven single nucleotide polymorphisms within TNFAIP3, STAT4, and IRF5, which are involved in upstream and downstream pathways of type I interferon production, in SLE in the South East Asian populations. Genotyping of 360 Malaysian SLE patients and 430 normal healthy individuals revealed that minor alleles of STAT4 rs7574865 and rs10168266 were associated with elevated risk of SLE in the Chinese and Malay patients, respectively (P = 0.028, odds ratio (OR) = 1.42; P = 0.035, OR = 1.80, respectively). Polymorphisms in TNFAIP3 and IRF5 did not show significant associations with SLE in any of the ethnicities. Combined analysis of the Malays, Chinese, and Indians for each SNP indicated that STAT4 rs10168266 was significantly associated with the Malaysian SLE as a whole (P = 0.014; OR = 1.435). The meta-analysis of STAT4 rs10168266, which combined the data of other studies and this study, further confirmed its importance as the risk factor for SLE by having pooled OR of 1.559 and P value of <0.001.
Study site: University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Measurement of von Willebrand factor antigen (VWF : Ag) levels is usually performed in a specialised laboratory which limits its application in routine clinical practice. So far, no commercial rapid test kit is available for VWF : Ag estimation. This paper discusses the technical aspect of latex agglutination method which was established to suit the purpose of estimating von Willebrand factor (VWF) levels in the plasma sample. The latex agglutination test can be performed qualitatively and semiquantitatively. Reproducibility, stability, linearity, limit of detection, interference, and method comparison studies were conducted to evaluate the performance of this test. Semiquantitative latex agglutination test was strongly correlated with the reference immunoturbidimetric assay (Spearman's rho = 0.946, P < 0.001, n = 132). A substantial agreement (κ = 0.77) was found between qualitative latex agglutination test and the reference assay. Using the scoring system for the rapid latex test, no agglutination is with 0% VWF : Ag (control negative), 1+ reaction is equivalent to <20% VWF : Ag, and 4+ reaction indicates >150% VWF : Ag (when comparing with immunoturbidimetric assay). The findings from evaluation studies suggest that latex agglutination method is suitable to be used as a rapid test kit for the estimation of VWF : Ag levels in various clinical conditions associated with high levels and low levels of VWF : Ag.
Seven-valent pneumococcal conjugate vaccine (PCV7) was included in the UK national immunisation program in 2006, and this was replaced by thirteen-valent PCV in 2010. During this time, the carriage of vaccine-type Streptococcus pneumoniae decreased but pneumococcal carriage remained stable due to increases in non-vaccine-type S. pneumoniae. Carriage studies have been undertaken in various countries to monitor vaccine-type replacement and to help predict the serotypes, which may cause invasive disease. There has been less focus on how conjugate vaccines indirectly affect colonization of other nasopharyngeal bacteria. If the nasopharynx is treated as a niche, then bacterial dynamics are accepted to occur. Alterations in these dynamics have been shown due to seasonal changes, antibiotic use, and sibling/day care interaction. It has been shown that, following PCV7 introduction, an eradication of pneumococcal vaccine types has resulted in increases in the abundance of other respiratory pathogens including Haemophilus influenzae and Staphylococcus aureus. These changes are difficult to attribute to PCV7 introduction alone and these studies do not account for further changes due to PCV13 implementation. This review aims to describe nasopharyngeal cocarriage of respiratory pathogens in the PCV era.
Development of vaccines for infectious diseases has come a long way with recent advancements in adjuvant developments and discovery of new antigens that are capable of eliciting strong immunological responses for sterile eradication of disease. Tuberculosis (TB) that kills nearly 2 million of the population every year is also one of the highlights of the recent developments. The availability or not of diagnostic methods for infection has implications for the control of the disease by the health systems but is not related to the immune surveillance, a phenomenon derived from the interaction between the bacteria and their host. Here, we will review the immunology of TB and current vaccine candidates for TB. Current strategies of developing new vaccines against TB will also be reviewed in order to further discuss new insights into immunotherapeutic approaches involving adjuvant and antigens combinations that might be of potential for the control of TB.
The field of osteoimmunology has emerged in response to the range of evidences demonstrating the close interrelationship between the immune system and bone metabolism. This is pertinent to immune-mediated diseases, such as rheumatoid arthritis and periodontal disease, where there are chronic inflammation and local bone erosion. Periprosthetic osteolysis is another example of chronic inflammation with associated osteolysis. This may also involve immune mediation when occurring in a patient with rheumatoid arthritis (RA). Similarities in the regulation and mechanisms of bone loss are likely to be related to the inflammatory cytokines expressed in these diseases. This review highlights the role of immune-related factors influencing bone loss particularly in diseases of chronic inflammation where there is associated localized bone loss. The importance of the balance of the RANKL-RANK-OPG axis is discussed as well as the more recently appreciated role that receptors and adaptor proteins involved in the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway play. Although animal models are briefly discussed, the focus of this review is on the expression of ITAM associated molecules in relation to inflammation induced localized bone loss in RA, chronic periodontitis, and periprosthetic osteolysis, with an emphasis on the soluble and membrane bound factor osteoclast-associated receptor (OSCAR).
Avian infectious bronchitis (IB) is a widely distributed poultry disease that has huge economic impact on poultry industry. The continuous emergence of new IBV genotypes and lack of cross protection among different IBV genotypes have been an important challenge. Although live attenuated IB vaccines remarkably induce potent immune response, the potential risk of reversion to virulence, neutralization by the maternal antibodies, and recombination and mutation events are important concern on their usage. On the other hand, inactivated vaccines induce a weaker immune response and may require multiple dosing and/or the use of adjuvants that probably have potential safety risks and increased economic burdens. Consequently, alternative IB vaccines are widely sought. Recent advances in recombinant DNA technology have resulted in experimental IB vaccines that show promise in antibody and T-cells responses, comparable to live attenuated vaccines. Recombinant DNA vaccines have also been enhanced to target multiple serotypes and their efficacy has been improved using delivery vectors, nanoadjuvants, and in ovo vaccination approaches. Although most recombinant IB DNA vaccines are yet to be licensed, it is expected that these types of vaccines may hold sway as future vaccines for inducing a cross protection against multiple IBV serotypes.
Tuberculosis (TB) is an airborne infection caused by Mycobacterium tuberculosis (Mtb). About one-third of the world's population is latently infected with TB and 5-15% of them will develop active TB in their lifetime. It is estimated that each case of active TB may cause 10-20 new infections. Host immune response to Mtb is influenced by interferon- (IFN-) signaling pathways, particularly by type I and type II interferons (IFNs). The latter that consists of IFN-γ has been associated with the promotion of Th1 immune response which is associated with protection against TB. Although this aspect remains controversial at present due to the lack of established correlates of protection, currently, there are different prophylactic, diagnostic, and immunotherapeutic approaches in which IFNs play an important role. This review summarizes the main aspects related with the biology of IFNs, mainly associated with TB, as well as presents the main applications of these cytokines related to prophylaxis, diagnosis, and immunotherapy of TB.
Tumour-associated macrophage (TAM) serves as the site in which most inflammatory cells coreside. It plays an important role in determining the progression and metastasis of a tumour. The characteristic of TAM is largely dependent on the stimuli present in its tumour microenvironment (TME). Under this environment, however, M2 macrophages are found to be in abundance compared to M1 macrophages which later promote tumour progression. Numerous studies have elucidated the relationship between TAM and the progression of tumour; hence, TAM has now been the subject of interest among researchers for anticancer therapy. This review discusses the role of TAM in colorectal cancer (CRC) and some of the potential candidates that could reeducate TAM to fight against CRC. It is with hope that this review will serve as the foundation in understanding TAM in CRC and helping other researchers to select the most suitable candidate to reeducate TAM that could assist in enhancing the tumouricidal activity of M1 macrophage and eventually repress the development of CRC.
Cellular components of the tumour microenvironment (TME) are recognized to regulate the hallmarks of cancers including tumour proliferation, angiogenesis, invasion, and metastasis, as well as chemotherapeutic resistance. The linkage between miRNA, TME, and the development of the hallmarks of cancer makes miRNA-mediated regulation of TME a potential therapeutic strategy to complement current cancer therapies. Despite significant advances in cancer therapy, lung cancer remains the deadliest form of cancer among males in the world and has overtaken breast cancer as the most fatal cancer among females in more developed countries. Therefore, there is an urgent need to develop more effective treatments for NSCLC, which is the most common type of lung cancer. Hence, this review will focus on current literature pertaining to antitumour or protumourigenic effects elicited by nonmalignant stromal cells of TME in NSCLC through miRNA regulation as well as current status and future prospects of miRNAs as therapeutic agents or targets to regulate TME in NSCLC.
Alternanthera sessilis, an edible succulent herb, has been widely used as herbal drug in many regions around the globe. Inflammation is a natural process of the innate immune system, accompanied with the increase in the level of proinflammatory mediators, for example, nitric oxide (NO) and prostaglandin (PGE2); cytokines such as interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNFα); and enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via the activation and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit p65 due to the phosphorylation of inhibitory protein, IκBα. Inflammation over a short period of time is essential for its therapeutic effect. However, prolonged inflammation can be detrimental as it is related to many chronic diseases such as delayed wound healing, cardiovascular disease, arthritis, and autoimmune disorders. Therefore, ways to curb chronic inflammation have been extensively investigated. In line with that, in this present study, we attempted to study the suppression activity of the proinflammatory cytokines and mediators as a characteristic of anti-inflammatory action, by using stem extract of A. sessilis in the lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage cell line. The results showed that the extract has significantly inhibited the production of the proinflammatory mediators including NO and PGE2; cytokines comprising IL-6, IL-1β, and TNFα; and enzymes covering the iNOS and COX-2 by preventing the IκBα from being degraded, to inhibit the nuclear translocation of NF-κB subunit p65 in order to hinder the inflammatory pathway activation. These results indicated that the stem extract of A. sessilis could be an effective candidate for ameliorating inflammatory-associated complications.