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ID PMID Title PublicationDate abstract
26535712 NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple dise 2015 Oct 30 Using a meta-analysis framework, we investigated the association between the NLRP3 rs35829419 polymorphism and increased susceptibility to diverse diseases in humans. Relevant published studies were identified through a comprehensive and systematic electronic search, using the following scientific literature databases: Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, Chinese Biomedical, the Chinese Journal Full-Text, and the Weipu Journal. Statistical analysis of data extracted from the selected high quality studies was performed using the Version 12.0 STATA software. A total of 13 case-control studies met our stringent inclusion and exclusion criteria for the present meta-analysis. These 13 high quality studies contained relevant information on 7719 patients with various diseases and 7094 healthy controls. Our meta-analysis results showed that the NLRP3 gene rs35829419 C>A polymorphism was associated with a significantly increased risk of developing multiple diseases in humans under 5 genetic models (all P < 0.05). Data stratification and subgroup analysis based on the disease type revealed that rs35829419 C>A carriers displayed a markedly increase susceptibility to leprosy, colorectal cancer, HIV-1 infection, rheumatoid arthritis, abdominal aortic aneurysms, inflammatory bowel disease, ulcerative colitis, and atopic dermatitis. In summary, our meta-analysis results revealed the first identified strong correlation between the NLRP3 rs35829419 polymorphism and increased susceptibility to various diseases in humans.
26311525 Exploring the role of interleukin-22 in neurological and autoimmune disorders. 2015 Oct Interleukin-22 (IL-22) is a member of the IL-10 cytokine family that has recently gained attention in regard to its recognized pathogenic role in neurological and autoimmune disorders. The pathological involvement of IL-22 has been linked to Th17 cells that are involved in its production. Its biological activity results from its ability to bind to a heterodimeric receptor consisting of IL-22 receptor 1 (IL-22R1) and IL-10R2. Emerging evidence has identified IL-22 involvement in neurological diseases and autoimmune disorders such as Guillain-Barré Syndrome (GBS), multiple sclerosis (MS), Alzheimer's disease (AD), encephalitis, inflammatory myopathies, myasthenia gravis (MG), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), psoriasis and Crohn's disease (CD). However, the biological activity of IL-22 is variable resulting in protective or pathogenic effects in different disease states. As such, the development of therapeutic targeting strategies to modify the biological activity of IL-22 is being explored as a promising interventional approach to treat neurological and autoimmune diseases.
26158901 Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor 2015 Sep 8 Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.
26130255 Bortezomib Inhibits Osteoclastogenesis and Porphyromonas gingivalis Lipopolysaccharide-ind 2015 Sep Healthy bone is maintained by the coordinated activities of osteoblast-mediated bone formation and osteoclast-dependent bone resorption. Pathologic conditions such as hormonal imbalance and inflammation cause increased osteoclastogenesis resulting in osteoporosis, rheumatoid arthritis, and periodontitis. Bortezomib is novel antimyeloma agent that has a direct beneficial effect on bone formation. However, the role of bortezomib in osteoclastogenesis and underlying mechanisms remains to be fully comprehended. In the present study, we show that bortezomib directly inhibited the receptor activator of nuclear factor κB ligand (RANKL)- and lipopolysaccharide-dependent osteoclast differentiation. Interestingly, the bortezomib-mediated inhibition of osteoclastogenesis was transient, since the removal of bortezomib from culture completely restored osteoclast differentiation. Bortezomib impeded the induction and nuclear localization of nuclear factor of activated T cells, cytoplasmic 1 and reduced both macrophage colony-stimulating factor- and RANKL-induced extracellular-signal-regulated kinase (ERK) phosphorylation. In a mouse model of periodontitis, bortezomib prevented alveolar bone erosion induced by Porphyromonas gingivalis lipopolysaccharide. These data not only suggest a previously unappreciated mechanism by which bortezomib regulates bone resorption but also propose novel applications of bortezomib beyond its use as an antimyeloma agent.
26097419 Studies on the Labeling of Ethylenediaminetetramethylene Phosphonic Acid, Methylene Diphos 2015 May For the treatment of skeletal metastasis, a therapeutic radionuclide tagged with a bone seeking ligand is required, while for radiation synovectomy (RS), a therapeutic radionuclide irreversibly attached to pre-formed particles of appropriate size is required. Radio lanthanides are mostly therapeutic, and ligands containing phosphate groups are predominantly bone seekers. Exploiting these facts, number of new therapeutic radiopharmaceuticals could be developed. Labeling of four phosphate containing materials was pursued in the present study. It was hypothesized that various (177)Lu-labeled bone-seeking complexes such as (177)Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP), (177)Lu-methylene diphosphonate (MDP) and (177)Lu-pyrophosphate (PYP) could be developed as agents for palliative radiotherapy of bone pain due to skeletal metastases, and (177)Lu-Hydroxyapatite (HA) could be developed as an agent for radiosynovectomy of small joints. Lyophilized kit vials of EDTMP, MDP and sodium pyrophosphate (Na-PYP) were formulated. HA particles were synthesized locally and purity was checked by high-performance liquid chromatography (HPLC). (177)Lu was labeled with EDTMP, MDP, PYP, and HA and the behavior of all was studied by radio-thin layer chromatography (TLC) radio-HPLC and radio-electrophoresis. Radio-TLC confirmed the labeling. HPLC analysis too verified the labeling. Radio-electrophoresis results depicted peaks for (177)Lu-MDP, (177)Lu-EDTMP and (177)Lu-PYP at 3.37 ± 0.06 cm, 5.53 ± 0.15 cm and 7.03 ± 0.06 cm respectively confirming negative charge on each specie as all migrated toward positive anode. All 3 methods verified the labeling. The study demonstrated that EDTMP, MDP and PYP form stable complexes with (177)Lu in injectable solution form. HA particulates could too be labeled with (177)Lu with high radiochemical yields (>98%) in suspension form. Former three could be utilized as bone-pain palliation agents for the treatment of bone metastases, and the later could be applied for the treatment of Rheumatoid arthritis of small joints. The study has also indicated the possibility of developing other numerous radiolanthanide analogs with the potentials of possible use in radiation therapy.
26068016 Lipocarbazole, an efficient lipid peroxidation inhibitor anchored in the membrane. 2015 Aug 1 Lipid peroxidation is a major deleterious effect caused by oxidative stress. It is involved in various diseases such as atherosclerosis, rheumatoid arthritis and neurodegenerative diseases. In order to inhibit lipid peroxidation, antioxidants must efficiently scavenge free radicals and penetrate inside biological membranes. Lipocarbazole has recently been shown to be a powerful antioxidant in solution. Here, we show its powerful capacity as lipid peroxidation inhibitor. Its mechanism of action is rationalized based on molecular dynamics simulations on a biomembrane model, quantum calculations and experimental evaluation. The role of the lipocarbazole side chain is particularly highlighted as a critical chemical feature responsible for its antioxidant activity.
25897949 Smoking is associated with increased levels of extracellular peptidylarginine deiminase 2 2015 May OBJECTIVES: Smoking is a well-established risk factor in rheumatoid arthritis (RA), and citrullination of self-antigens plays a pathogenic role in the majority of patients. Increased numbers of peptidylarginine deiminase 2 (PAD2)-containing macrophages have been demonstrated in bronchoalveolar lavage (BAL) fluid from smokers, but intracellularly located PAD cannot be responsible for citrullination of extracellular self-antigens. We aimed to establish a link between smoking and extracellular PAD2 in the lungs. METHODS: BAL fluid samples were obtained from 13 smokers and 11 nonsmoking controls. Total protein content and C-reactive protein (CRP) concentration were determined after separating cells from the samples. PAD2 content in cell-free BAL fluids was measured by means of a PAD2-specific sandwich ELISA. RESULTS: Significantly increased levels of soluble PAD2 were detected in cell-free BAL fluids from smokers as compared to non-smokers (p=0.018). The PAD2 content correlated with the overall CRP levels (p=0.009) and cell count (p=0.016). CONCLUSIONS: This first demonstration of increased levels of extracellular PAD2 in the lungs of smokers supports the hypothesis that smoking promotes extracellular citrullination of proteins. This may represent a pathological event upstream for the production of anti-citrullinated protein antibodies (ACPAs) among RA patients carrying HLA-molecules capable of binding citrullinated self-peptides.
25849052 The role of nailfold capillaroscopy in interstitial lung diseases - can it differentiate i 2015 INTRODUCTION: Nailfold capillaroscopy (NFC) is a non-invasive diagnostic test that is mostly used for early diagnosis of collagen tissue diseases (CTDs). We aimed to evaluate whether NFC findings could be a clue for discriminating idiopathic interstitial lung diseases (ILD) from CTD associated ILDs (CTD-ILD). Additionally it was aimed to determine whether NFC could be helpful in discriminating usual interstitial pneumonia (UIP) pattern from non-specific interstitial pneumonia (NSIP) pattern. MATERIALS AND METHODS: We grouped patients into three main groups: 15 CTD-ILD, 18 idiopathic ILD, and 17 patients in the control group. The CTD-ILD group was split into two subgroups: 8 patients with Sjögren's syndrome (SJS)-associated ILD and 7 with rheumatoid arthritis (RA)-associated ILD. The idiopathic-ILD group consisted of 10 idiopathic NSIP and 8 IPF patients. The control group consisted of 10 SJS and 7 RA patients without lung disease. None of the patients were on acute exacerbation at the time of examination, and none had Reynaud's phenomenon. RESULTS: Mean capillary density was significantly reduced only in the CTD-ILD group as compared to the control group (p= 0.006). In subgroup analysis, it was determined that RA-ILD, IPF, and SJS-ILD subgroups had more severe capillaroscopic abnormalities. Mean capillary density in patients with the UIP pattern was reduced compared to patients with the NSIP pattern and those in the control group; p values were 0.008 and < 0.001, respectively. CONCLUSION: This study is to be the first describing and comparing the nailfold capillaroscopic findings of patients with NSIP and UIP patterns. NFC findings can be helpful in discriminating UIP patterns from NSIP patterns. But to show its role in differentiating idiopathic disease, more studies with more patients are needed.
25786575 Expression of anti-tumor necrosis factor alpha (TNFα) single-chain variable fragment (scF 2016 May Therapeutic antibodies against tumor necrosis factor alpha (TNFα) have been considered effective for some of the autoimmune diseases such as rheumatoid arthritis, Crohn's diseases, and so on. But associated limitations of the current therapeutics in terms of cost, availability, and immunogenicity have necessitated the need for alternative candidates. Single-chain variable fragment (scFv) can negate the limitations tagged with the anti-TNFα therapeutics to a greater extent. In the present study, Spirodela punctata plants were transformed with anti-TNFα through in planta transformation using Agrobacterium tumefaciens strain, EHA105. Instead of cefotaxime, garlic extract (1 mg/mL) was used to remove the agrobacterial cells after cocultivation. To the best of our knowledge, this report shows for the first time the application of plant extracts in transgenic plant development. 95% of the plants survived screening under hygromycin. ScFv cDNA integration in the plant genomic DNA was confirmed at the molecular level by PCR. The transgenic protein expression was followed up to 10 months. Expression of scFv was confirmed by immunodot blot. Protein expression levels of up to 6.3% of total soluble protein were observed. β-Glucuronidase and green fluorescent protein expressions were also detected in the antibiotic resistant plants. The paper shows the generation of transgenic Spirodela punctuata plants through in planta transformation.
31641575 Decreased serum level of thioredoxin 1 in female patients with pneumonia and its combinati 2015 Thioredoxin 1 (Trx1) and haptoglobin (Hp) are known to be involved in pathophysiology. This study was conducted to evaluate their diagnostic significance. We employed an enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of both Trx1 and Hp in sera from female patients with community-acquired pneumonia (CAP) and those with lung cancer. The Trx1 levels remarkably decreased in cases of female patients with CAP, while the Hp levels increased in both female patients with lung cancer and CAP. In addition, the serum levels of Trx1 were not significantly changed in patients with lung cancer, rheumatoid arthritis, and cardiovascular diseases compared to healthy controls. At the cut-off point of 0.396 at A(450 nm) on the receiver operating characteristic (ROC) curve, Trx1 could discriminate between patients with CAP from normal female controls with a sensitivity of 72.5%, a specificity of 89.8%, and area under the ROC curve (AUC) of 0.877 ± 0.040. The serum levels of Trx1 in female CAP patients were inversely correlated with the levels of Hp (p < 0.05). The characteristic reduction in serum Trx1 levels, especially in female CAP patients, indicates that Trx1 could be used as a diagnostic marker for CAP. The advantage of serum Trx1 over Hp in discriminating female CAP patients among female patients who have a positive serum level of Hp suggests the use of Trx1 as an excellent combination marker with Hp for the specific diagnosis of CAP and lung carcinoma, because serum Hp levels increase in female patients with lung cancer and those with CAP without selectivity.
26487169 Fatigue is correlated with disease activity but not with the type of organ involvement in 2015 Nov OBJECTIVES: Fatigue is an important problem in inflammatory diseases and affects the quality of life (QoL). We aimed to evaluate the severity and impact of fatigue in Behçet's syndrome (BS) and to determine its association with type of organ involvement and gender. METHODS: One hundred and fifty-two BS, 51 rheumatoid arthritis (RA), 51 systemic lupus erythematosus (SLE), 51 ankylosing spondylitis (AS) patients and 65 healthy controls were evaluated by the fatigue severity scale, fatigue impact scale, fibromyalgia impact questionnaire (FIQ), RAPID3, SF-36 and Behçet's syndrome activity scale (the latter only in BS patients). We also analysed subgroups of BS patients with predominantly eye, vascular, joint and mucocutaneous involvement and did an additional gender analysis. RESULTS: Fatigue severity and fatigue impact scores were similar among BS, RA, SLE and AS patients and significantly higher than that in healthy controls (F4df=8.51; p<0.001 and F4df=8.67; p<0.001, respectively). The fatigue severity and fatigue impact scores were similarly high in BS subgroups with different types of organ involvement, and in both genders. CONCLUSIONS: Fatigue is an important problem in BS, as it is in other inflammatory conditions. It is similarly severe in subgroups of patients with eye, vascular, joint and mucocutaneous involvement and in either gender. Fatigue is a candidate outcome measure for clinical trials, to assess the life impact of Behçet's syndrome.
26436484 Mean platelet volume is elevated in exacerbated and convalescent COPD patients. 2015 Dec 7 BACKGROUND: Mean platelet volume (MPV), reflecting the platelet production rate and stimulation, is an inflammatory marker for cardiovascular disease, inflammatory bowel disease, and rheumatoid arthritis. However, the associations between MPV and chronic obstructive pulmonary disease (COPD) are not in agreement. METHODS: Ninety participants with an exacerbation of COPD were investigated, and were reassessed when convalescent. Ninety controls were matched for age, gender, body mass index, smoking index, and medication use. Blood samples were collected for measurements of MPV and other laboratory data, and pulmonary function was also assessed. RESULTS: MPV is significantly increased in convalescent COPD patients compared with healthy controls, and further increased in COPD patients with an acute exacerbation. MPV was positively correlated with high-sensitivity C-reactive protein both in the exacerbation and convalescence periods of COPD, and negatively correlated with FEV1 % predicted and FEV1/FVC in the convalescent COPD patients. CONCLUSIONS: MPV may be regarded as a quick and reliable tool in the assessment of inflammatory response in the progression of COPD.
25989481 Emerging role of long noncoding RNAs in autoimmune diseases. 2015 Sep Long noncoding RNA (lncRNA), with size larger than 200 nucleotides, is a new class of noncoding RNA. Emerging evidence has revealed that lncRNAs play a key role in the regulation of immunological functions and autoimmunity. Herein, we review the recent findings of lncRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. In addition, we focus on the involvement of lncRNA regulation in innate and adaptive immune responses, immune cell development, and differential expression of lncRNAs in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), multiple sclerosis (MS), autoimmune thyroid disease (AITD), psoriasis, polymyositis/dermatomyositis (PM/DM) and Crohn's disease (CD).
25891380 Autoimmune connective tissue diseases. 2015 Jul Rheumatic diseases (RDs) occur preferentially in women, often during the childbearing age. The interaction of pregnancy and the RD is varied, ranging from spontaneous improvement to aggravation of disease symptoms or life-threatening flares. Risks for the mother with RD and the child differ in regard to the presence of organ manifestations, organ damage, disease activity, presence of specific autoantibodies, and therapy. Pregnancy complications comprise hypertension, preeclampsia, premature delivery, and side effects of therapy. Adverse pregnancy outcomes include recurrent miscarriage, intrauterine growth restriction, and fetal demise, and they are frequently encountered in RD with organ manifestations and harmful autoantibodies. Because of the difference in the prevalence of RDs, knowledge on the gestational course of disease and pregnancy outcome is limited to the fairly common RDs such as rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome. Pregnancies in RD are connected with increased risks for mother and child and need interdisciplinary care and management.
25620685 Plantar pressure relief under the metatarsal heads: therapeutic insole design using three- 2015 Feb 26 Therapeutic footwear with specially-made insoles is often used in people with diabetes and rheumatoid arthritis to relieve ulcer risks and pain due to high pressures from areas beneath bony prominences of the foot, in particular to the metatarsal heads (MTHs). In a three-dimensional finite element study of the foot and footwear with sensitivity analysis, effects of geometrical variations of a therapeutic insole, in terms of insole thicknesses and metatarsal pad (MP) placements, on local peak plantar pressure under MTHs and stress/strain states within various forefoot tissues, were determined. A validated musculoskeletal finite element model of the human foot was employed. Analyses were performed in a simulated muscle-demanding instant in gait. For many design combinations, increasing insole thicknesses consistently reduce peak pressures and internal tissue strain under MTHs, but the effects reach a plateau when insole becomes very thick (e.g., a value of 12.7mm or greater). Altering MP placements, however, showed a proximally- and a distally-placed MP could result in reverse effects on MTH pressure-relief. The unsuccessful outcome due to a distally-placed MP may attribute to the way it interacts with plantar tissue (e.g., plantar fascia) adjacent to the MTH. A uniform pattern of tissue compression under metatarsal shaft is necessary for a most favorable pressure-relief under MTHs. The designated functions of an insole design can best be achieved when the insole is very thick, and when the MP can achieve a uniform tissue compression pattern adjacent to the MTH.
25439045 The role of serotonin and its receptors in activation of immune responses and inflammation 2015 Mar Serotonin or 5-hydroxytryptamine (5-HT) is a neurotransmitter and hormone that contributes to the regulation of various physiological functions by its actions in the central nervous system (CNS) and in the respective organ systems. Peripheral 5-HT is predominantly produced by enterochromaffin (EC) cells of the gastrointestinal (GI) tract. These gut-resident cells produce much more 5-HT than all neuronal and other sources combined, establishing EC cells as the main source of this biogenic amine in the human body. Peripheral 5-HT is also a potent immune modulator and affects various immune cells through its receptors and via the recently identified process of serotonylation. Alterations in 5-HT signalling have been described in inflammatory conditions of the gut, such as inflammatory bowel disease. The association between 5-HT and inflammation, however, is not limited to the gut, as changes in 5-HT levels have also been reported in patients with allergic airway inflammation and rheumatoid arthritis. Based on searches for terms such as '5-HT', 'EC cell', 'immune cells' and 'inflammation' in pubmed.gov as well as by utilizing pertinent reviews, the current review aims to provide an update on the role of 5-HT in biological functions with a particular focus on immune activation and inflammation.
28001129 A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature. 2017 Feb Quantification of blood oxygen saturation (SO(2)) in vivo is essential for understanding the pathogenesis of diseases in which hypoxia is thought to play a role, including inflammatory disorders such as multiple sclerosis (MS) and rheumatoid arthritis (RA). We describe a low-cost multispectral microscope and oximetry technique for calibration-free absolute oximetry of surgically exposed blood vessels in vivo. We imaged the vasculature of the dorsal spinal cord in healthy rats, and varied inspired oxygen (FiO(2)) in order to evaluate the sensitivity of the imaging system to changes in SO(2). The venous SO(2) was calculated as 67.8  ±  10.4% (average  ±  standard deviation), increasing to 83.1  ±  11.6% under hyperoxic conditions (100% FiO(2)) and returning to 67.4  ±  10.9% for a second normoxic period; the venous SO(2) was 50.9  ±  15.5% and 29.2  ±  24.6% during subsequent hypoxic states (18% and 15% FiO(2) respectively). We discuss the design and performance of our multispectral imaging system, and the future scope for extending this oximetry technique to quantification of hypoxia in inflamed tissue.
27956668 The inflammasome as a target for pain therapy. 2016 Dec The interleukin-1 family of cytokines are potent inducers of inflammation and pain. Proteolytic activation of this family of cytokines is under the control of several innate immune receptors that coordinate to form large multiprotein signalling platforms, termed inflammasomes. Recent evidence suggests that a wide range of inflammatory diseases, cancers, and metabolic and autoimmune disorders, in which pain is a common complaint, may be coordinated by inflammasomes. Activation of inflammasomes results in cleavage of caspase-1, which subsequently induces downstream initiation of several potent pro-inflammatory cascades. Therefore, it has been proposed that targeting inflammasome activity may be a novel and effective therapeutic strategy for these pain-related diseases. The purpose of this narrative review article is to provide the reader with an overview of the activation and regulation of inflammasomes and to investigate the potential therapeutic role of inflammasome inhibition in the treatment of diseases characterized by pain, including the following: complex regional pain syndrome, gout, rheumatoid arthritis, inflammatory pain, neuropathic pain, chronic prostatitis, chronic pelvic pain syndrome, and fibromyalgia. We conclude that the role of the inflammasome in pain-associated diseases is likely to be inflammasome subtype and disease specific. The currently available evidence suggests that disease-specific targeting of the assembly and activity of the inflammasome complex may be a novel therapeutic opportunity for the treatment of refractory pain in many settings.
27881864 Mass spectrometry imaging: a novel technology in rheumatology. 2017 Jan Mass spectrometry imaging (MSI) is used to determine the relative abundance and spatial distribution of biomolecules such as peptides, proteins, lipids and other organic compounds in tissue sections by their molecular masses. This technique provides a sensitive and label-free approach for high-resolution imaging, and is currently used in an increasing number of biomedical applications such as biomarker discovery, tissue classification and drug monitoring. Owing to technological advances in the past 5 years in diverse MSI strategies, this technology is expected to become a standard tool in clinical practice and provides information complementary to that obtained using existing methods. Given that MSI is able to extract mass-spectral signatures from pathological tissue samples, this technique provides a novel platform to study joint-related tissues affected by rheumatic diseases. In rheumatology, MSI has been performed on articular cartilage, synovium and bone to increase the understanding of articular destruction and to characterize diagnostic and prognostic biomarkers for osteoarthritis, rheumatoid arthritis and osteoporosis. In this Review, we provide an overview of MSI technology and of the studies in which joint tissues have been analysed by use of this methodology. This approach might increase knowledge of rheumatic pathologies and ultimately prompt the development of targeted strategies for their management.
27869438 Immunology Update: Biologics. 2016 Nov Biologics are substances made from a living organism or its products. These include genes, proteins (eg, antibodies, receptors, enzymes, inhibitors), recombinant proteins, and fusion proteins. Biologics often are produced using recombinant DNA technology. For example, monoclonal antibodies are produced by inserting human genes into immortalized cell cultures, which then produce the gene product (ie, an antibody) in large quantity. Another approach is to fuse genetic material from nonhuman sources (eg, mice) with human genetic material. The fused gene is inserted into a tissue culture that produces the gene product (ie, a chimeric monoclonal antibody). Biologics are used to manage many conditions, including malignant and nonmalignant conditions. They are widely used in the treatment of human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])-positive breast cancer. They also are used in the treatment of leukemias, lymphomas, and colorectal and lung cancer. Biologics improve outcomes in autoimmune disorders, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, inflammatory bowel disease, and multiple sclerosis. Other uses include erythropoietin for renal failure-associated anemia and the new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for treatment of patients with persistently elevated low-density lipoprotein levels despite statin treatment who are at high risk of cardiovascular events.